Renal Physiology

Xiaohong Xia

夏晓红

Department of Physiology

Hebei Medical University

E-mail xiaunmchotmailcom)

About this Chapter

bull Anatomy of the excretory system

bull How the kidney is organized

bull How the nephron works to filter blood

recycle secrete and excrete

bull How filtration is regulated

bull Urination reflex

Kidney Function

1 Regulation of water and inorganic ions

balance

2 Excretion of metabolic waste products

3 Removing of foreign chemicals

by producingexcreting urine

to maintain the internal homeostasis

of the body

Kidney Function

4 Secretion of hormones

a Erythropoietin (EPO --- is produced by

interstitial cells in peritubular capillary)

which controls erythrocyte production

b Renin ( is produced by juxtaglomerular cell)

which controls formation of angiotensin

c 125-dihydroxyvitamin D3

which influences calcium balance

Outline

bull 1048715 Functional Anatomy of Kidneys and Renal

Circulation

bull 1048715 Glomerular Filtration

bull 1048715 Tubular Processing of Urine Formation

bull 1048715 Urine Concentration and Dilution

bull 1048715 Regulation of Water and Sodium Excretion

bull 1048715 Renal Clearance

bull 1048715 Urine Volume and Micturition

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

About this Chapter

bull Anatomy of the excretory system

bull How the kidney is organized

bull How the nephron works to filter blood

recycle secrete and excrete

bull How filtration is regulated

bull Urination reflex

Kidney Function

1 Regulation of water and inorganic ions

balance

2 Excretion of metabolic waste products

3 Removing of foreign chemicals

by producingexcreting urine

to maintain the internal homeostasis

of the body

Kidney Function

4 Secretion of hormones

a Erythropoietin (EPO --- is produced by

interstitial cells in peritubular capillary)

which controls erythrocyte production

b Renin ( is produced by juxtaglomerular cell)

which controls formation of angiotensin

c 125-dihydroxyvitamin D3

which influences calcium balance

Outline

bull 1048715 Functional Anatomy of Kidneys and Renal

Circulation

bull 1048715 Glomerular Filtration

bull 1048715 Tubular Processing of Urine Formation

bull 1048715 Urine Concentration and Dilution

bull 1048715 Regulation of Water and Sodium Excretion

bull 1048715 Renal Clearance

bull 1048715 Urine Volume and Micturition

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Kidney Function

1 Regulation of water and inorganic ions

balance

2 Excretion of metabolic waste products

3 Removing of foreign chemicals

by producingexcreting urine

to maintain the internal homeostasis

of the body

Kidney Function

4 Secretion of hormones

a Erythropoietin (EPO --- is produced by

interstitial cells in peritubular capillary)

which controls erythrocyte production

b Renin ( is produced by juxtaglomerular cell)

which controls formation of angiotensin

c 125-dihydroxyvitamin D3

which influences calcium balance

Outline

bull 1048715 Functional Anatomy of Kidneys and Renal

Circulation

bull 1048715 Glomerular Filtration

bull 1048715 Tubular Processing of Urine Formation

bull 1048715 Urine Concentration and Dilution

bull 1048715 Regulation of Water and Sodium Excretion

bull 1048715 Renal Clearance

bull 1048715 Urine Volume and Micturition

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Kidney Function

4 Secretion of hormones

a Erythropoietin (EPO --- is produced by

interstitial cells in peritubular capillary)

which controls erythrocyte production

b Renin ( is produced by juxtaglomerular cell)

which controls formation of angiotensin

c 125-dihydroxyvitamin D3

which influences calcium balance

Outline

bull 1048715 Functional Anatomy of Kidneys and Renal

Circulation

bull 1048715 Glomerular Filtration

bull 1048715 Tubular Processing of Urine Formation

bull 1048715 Urine Concentration and Dilution

bull 1048715 Regulation of Water and Sodium Excretion

bull 1048715 Renal Clearance

bull 1048715 Urine Volume and Micturition

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Outline

bull 1048715 Functional Anatomy of Kidneys and Renal

Circulation

bull 1048715 Glomerular Filtration

bull 1048715 Tubular Processing of Urine Formation

bull 1048715 Urine Concentration and Dilution

bull 1048715 Regulation of Water and Sodium Excretion

bull 1048715 Renal Clearance

bull 1048715 Urine Volume and Micturition

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

SECTION 1

Functional Anatomy of Kidneys and

Renal Circulation

Urinary system

paired kidneys

paired ureters

a bladder

a urethra

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

The kidney renal cortex

renal medulla

renal pelvis

Anatomical Characteristics of the Kidney

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

1 Nephrons functional unit of kidneys

(1) Consist of nephron

bull Nephron is the basic smallest functional unit

of kidney

bull Nephron consists of renal corpuscle and renal

tubule

bull Each kidney is composed of about 1 million

microscopic functional unit

Anatomical Characteristics of the Kidney

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Consist of Nephron

Nephron

renal corpuscle

glomerulus

Bowmanrsquos capsule

renal tubule

proximal tubule

thin segment

distal tubule

proximal convoluted tubule

thick descending limb

thin descending limb

thin ascending limb

thick ascending limb

distal convoluted tubule

loop of Henley

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Anatomical Characteristics of the Kidney

Functional unit -nephron

Corpuscle

Bowmanrsquos capsule

Glomerulus capillaries

Tubule

PCT

Loop of Henley

DCT

Collecting duct

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Two Types of Nephron

bull Cortical nephrons

bull ~85 of all nephrons

bull Located in the cortex

bull Juxtamedullary nephrons

bull Closer to renal medulla

bull Loops of Henle extend deep into renal pyramids

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

AA = EA

1

AA gt EA

2

Diameter of AA

Diameter of EA

To form Vasa recta To form Peritubular capillary EA

Poor Rich Sympathetic

nerve innervation

Almost no High Concentration of renin

10

Concentrate and dilute

urine

90

Reabsorption and secretion

Ratio

Function

Longer into inner part of

cortex

Short next to outer cortex Loop of Henle

Big Small Glomerulus

Inner part of the cortex

next to the medulla

Outer part of the cortex Location

Juxtamedullary nephron Cortical nephron

AA = afferent glomerular arteriole

EA = efferent glomerular arteriole

Tab 8-1 Differences between a cortical and a Juxtamedullary nephron

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Cortical and Juxtamedullary Nephrons

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

2 Collecting duct

Function As same as distal tubular

3 Juxaglomerular apparatus (JGA)

macula densa --- in initial portion of DCT

Function sense change of volume and NaCl

concentration of tubular fluid and transfer

information to JGC

mesangial cell

juxtaglomerular cell (JGC) --- in walls of the afferent

arterioles)

Function secrete renin

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Juxaglomerular apparatus

JA locate in cortical nephron consist of juxtaglomerular

cell mesangial cell and macula densa

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Tubulo-glomerular Feedback

bull Macula densa can detects Na+ K+ and Cl-

of tubular fluid and then sent some

information to glomerule regulation

releasing of renin and glomerular filtration

rate This process is called Tubulo-

glomerullar feedback

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renal circulation

1Characteristics of renal blood circulation

bull Huge volumes blood

1200mlmin15 ndash 14 of the cardiac output

bull Distribution

Cortex 94 outer medulla 5 - 6 inner medulla lt1

bull Two capillary beds

Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renal circulation

bull Glomerular capillaries

Higher pressure benefit for filtration

bull Peritubular capillaries

Lower pressure benefit for reabsorption

bull Vasa recta

Concentrate and dilute urine

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renal circulation

Glomerular

capillary

cortex

medulla

Peritubular

capillary

vasa recta

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Regulation of renal blood flow

Autoregulation

When arterial pressure is in range of 80 to 180 mmHg renal

blood flow (RBF) is relatively constant in denervated isolated

or intact kidney

Flow autoregulation is a major factor that controls RBF

Mechanism of autoregulation myogenic theory of

autoregulation

Physiological significance

To maintain a relatively constant glomerular filtration rate

(GFR)

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Autoregulation of renal blood flow

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Neural regulation

Renal efferent nerve from brain to kidney

bull Renal sympathetic nerve

Renal afferent nerve from kidney to brain

bull Renal afferent nerve fiber can be stimulated

mechanical and chemical factors

renorenal reflex

One side renal efferent nerve activity can effect other side renal nerve activity

Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Hormonal regulation

Vasoconstriction

bull Angiotensin II

bull Epinephrine

bull Norepinephrine

Vasodilation

bull Prostaglandin

bull nitrous oxide

bull Bradykinin

RBF

RBF

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Basic processes for urine formation

Glomerular filtration

Most substances in blood except for protein and cells are

freely filtrated into Bowmans space

Reabsorption

Water and specific solutes are reabsorbed from tubular fluid

back into blood (peritubular capillaries)

Secretion

Some substances (waste products etc) are secreted from

peritubular capillaries or tubular cell interior into tubules

Amount Excreted = Amount filtered ndash Amount reabsorbed +

Amount secreted

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Three basic processes of the formation of urine

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Basic processes for urine formation

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Except for proteins the composition of glomerular filtrates is

same as that of plasma

1 Composition of the glomerular filtrates

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

2 Glomerular filtration membrane

The barrier between the

capillary blood and the

fluid in the Bowmanrsquos

space

Composition three layers

bull Capillary endothelium ---

fenestrations(70-90nm)

bull Basement membrane ---

meshwork

bull Epithelial cells (podocyte) -

--slit pores

Figure 2610a b

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Showing the filtration membran To be filtered a substance must pass

through 1 the pores between the endothelial cells of the glomerullar capillary

2 an cellular basement membrane and 3 the filtration slits between the foot

processes of the podocytes of the inner layer of Bowmanrsquos capsule

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Selective permeability of filtration

membrane

Structure Characteristics

There are many micropores in each layer

Each layer contains negatively charged glycoproteins

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Selective permeability of filtration

membrane

Size selection

impermeable to substances

with molecule weight (MW)

more than 69 000 or EMR 42 nm (albumin)

Charge selection

Repel negative charged substances

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Filtrate Composition bull Glomerular filtration barrier restricts the filtration of

molecules on the basis of size and electrical charge

bull Neutral solutes

bull Solutes smaller than 180 nanometers in radius are freely filtered

bull Solutes greater than 360 nanometers do not

bull Solutes between 180 and 360 nm are filtered to various degrees

bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)

bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Glomerular filtration rate (GFR)

The minute volume of plasma filtered through

the filtration membrane of the kidneys is called

the glomerular filtration rate

(Normally is 125mlmin)

bull Filtration fraction (FF)

The ratio of GFR and renal plasma flow

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Factors affecting glomerular filtration

bull Effective filtration pressure (EFP)

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic and colloid

osmotic forces that either favor or oppose filtration

across the glomerular capillaries

bull EFP is promotion of filtration

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Formation and calculate of EPF

Formation of EPF depends on three pressures

Glomerular capillary pressure (Pcap)

Plasma colloid osmotic pressure (Pcol)

Intracapsular pressure (Picap)

bull Calculate of EPF

EFP = Pcap ndash (Pcol + Picap)

bull Part of afferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10

bull Part of efferent arterial

EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Effective filtraton pressure

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Filtration Coefficient ( Kf )

bull Filtration coefficient is a minute volume of

plasma filtered through the filtration

membrane by unit effective filtration pressure

drive Kf =KtimesS

bull GFR is dependent on the filtration coefficient

as well as on the net filtration pressure

GFR=Ptimes Kf

bull The surface area the permeability of the

glomerular membrane can affect Kf

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

What kind of factors can affect filtration rate

1Effective filtration pressure

2Glomerular capillary pressure

3Plasma colloid osmotic pressure

4Intracapsular pressure

5Renal plasma flow

6Kf =KtimesS Kf filtration coefficient

K permeability coefficient

S surface area the permeability

Factors Affecting Glomerular Filtration

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Regulation of Glomerular Filtration

bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine

bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of

bull Control of GFR normally result from adjusting glomerular capillary blood pressure

bull Three mechanisms control the GFR

bull Renal autoregulation (intrinsic system)

bull Neural controls

bull Hormonal mechanism (the renin-angiotensin system)

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation

maintains a nearly constant glomerular filtration rate

bull Two mechanisms are in operation for autoregulation

bull Myogenic mechanism

bull Tubuloglomerular feedback

bull Myogenic mechanism

bull Arterial pressure rises afferent arteriole stretches

bull Vascular smooth muscles contract

bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant

bull Tubuloglomerular feed back mechanism for autoregulation

bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)

bull Increased GFR (amp RBF) triggers release of vasoactive signals

bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Extrinsic Controls

bull When the sympathetic nervous system is at rest

bull Renal blood vessels are maximally dilated

bull Autoregulation mechanisms prevail

bull Under stress

bull Norepinephrine is released by the sympathetic nervous system

bull Epinephrine is released by the adrenal medulla

bull Afferent arterioles constrict and filtration is inhibited

bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism

bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Response to a Reduction in the GFR

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renin-Angiotensin Mechanism

bull Renin release is triggered by

bull Reduced stretch of the granular JG cells

bull Stimulation of the JG cells by activated macula densa cells

bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves

bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II

bull Angiotensin II

bull Causes mean arterial pressure to rise

bull Stimulates the adrenal cortex to release aldosterone

bull As a result both systemic and glomerular hydrostatic pressure rise

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Figure 2510

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Other Factors Affecting Glomerular Filtration

bull Prostaglandins (PGE2 and PGI2)

bull Vasodilators produced in response to sympathetic stimulation and angiotensin II

bull Are thought to prevent renal damage when peripheral resistance is increased

bull Nitric oxide ndash vasodilator produced by the vascular endothelium

bull Adenosine ndash vasoconstrictor of renal vasculature

bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Control of Kf bull Mesangial cells have contractile properties influence

capillary filtration by closing some of the capillaries ndash

effects surface area

bull Podocytes change size of filtration slits

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Glomerular filtration

bull Tubular reabsorption of

the substance from the

tubular fluid into blood

bull Tubular secretion of the

substance from the blood

into the tubular fluid

bull Mass Balance

bull Amount Excreted in Urine =

Amount Filtered through

glomeruli into renal proximal

tubule MINUS amount

reabsorbed into capillaries

PLUS amount secreted into

the tubules

Process of Urine Formation

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Tubular Secretion

bull Essentially reabsorption in reverse where

substances move from peritubular capillaries or

tubule cells into filtrate

bull Tubular secretion is important for

bull Disposing of substances not already in the filtrate

bull Eliminating undesirable substances such as urea and

uric acid

bull Ridding the body of excess potassium ions

bull Controlling blood pH

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Tubular reabsorption and secretion

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

SECTION 3 Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion

Characteristics of reabsorption

quantitatively large

More than 99 volume of filtered fluid are reabsorbed

(gt 178L)

selective

100 glucose 99 sodium and chloride 85

bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

(1) Type of transportation in renal tubule and

colllecting duct

bull Reabsorption and secretion are divided two types

bull Passive reabsorption (needless energy)

Diffusion osmosis facilitated diffusion

bull Active reabsorption (need energy)

bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)

bull Cotransport (coupled transport)

One transportor can transport two or more substances

bull Symport transport like Na+ and glucose Na+ and amine acids

Antiport transport like Na+-H+ and Na+-K+

bull Secondary active transport like H+ secretion

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Na+ active transport in PT epithelium

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Passway of transport

Apical membrane tight juction brush border

basolateral membrane

bull Transcellular pathway

Na+ apical membrane epithelium Na+ pump peritubular

capillary

bull Paracellular transport

Water Cl- and Na+ tight juction peritubular capillary

K+ and Ca2+ are reabsorpted with water by solvent drag

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Fig8-23 The pathway of reabsorption

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Reabsorption of transcellular and paracellular pathway

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Na+ and Cl - paracellular reabsorption in PT epithelium

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Location of reabsorption

Proximal tubule

Brush border can increase the area of

reabsorption

Henles loop

Distal tubule

Collecting duct

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

(2) Reabsorption and secretion in different part of

renal tubule

bull Proximal tubule (PT)

67 Na+ Cl- K+ and water 85 HCO3- and 100

glucose and amine acids are reabsorption

secretion H+

23 Transcellular pathway

13 Paracellular transport

The key of reabsorption is Na+ reabsorption ( the

action of Na+ pump in the membrane of proximal

tubule)

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

1 Na+Cl- and water reabsorption

Na+ and Cl- reabsorption

bull About 65 - 70 in proximal tubule 10 in

distal tubule 20 loop of Henle

bull Valume of filtration 500gday

Valume of excretion 3 ndash 5g99 are

reabsorption

bull Front part of PT Na+ reabsorption with HCO3-

Glucose and Amine acids

Behind part of PT Na+ reabsorption with Cl-

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Cl- reabsorption

Passive reabsorption with Na+

bull water reabsorption

Passive reabsorption with Na+ and Cl-

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Na+ transcellular transportation in early part of PT epithelium

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Cl- passive reabsorption in later part of PT epithelium

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Water passive reabsorption

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

K+ reabsorption

Most of in PT (70)20 in loop of Henle

Active reabsorption

Ca2+ reabsorption

70 in PT 20 in loop of Henle 9 in DCT

20 is transcellular pathway

80 is paracellular transport

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

HCO -3 reabsorption and H+ secretion

bull About 80 in PT 15 in ascending thick limb 5 in

DCT and CD

bull H2CO3 CO2 + H2O CO2 is easy reabsorption

bull HCO3ndash reabsorption is priority than Cl-

H+ secretion

bull CO2 + H2O H2CO3 HCO3ndash+ H

+

bull H+ secretion into lumen

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Bicarbonate reabsorption

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Glucose and amino acid reabsorption

Glucose reabsorption 99 glucose are reabsorption no glucose in urine

bull Location

early part of PT

bull Type of reabsorption

secondary active transport

bull Renal glucose threshold

When the plasma glucose concentration increases up to a

value about 160 to 180 mg per deciliter glucose can first

be detected in the urine this value is called the renal

glucose threshold

9-101 mmolL (160-180mgdl)

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Glucose secondary active transport in early part of PT

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Transport maximum (Tm) 转运极限

Transport maximum is the maximum rate at which

the kidney active transport mechanisms can

transfer a particular solute into or out of the

tubules

Amino acid reabsorption

Location and type of reabsorption as same as

glucose

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Glucose secondary active transport in early part of PT

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Co-transport of amino acids via Na+ symport mechanism

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Loop of Henle

Ascending thick limb of loop of Henle

Na+ Cl- and K+ cotransport

Transportation rate Na+ 2Cl- K+

Distal tubule and collecting duct

Principal cell Reabsorption Na+ water and

secretion K+

Intercalated cell Secretion H+

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct

bull Water reabsorption depends on whether lack of

water of body ADH (discuss later)

bull Na+ and K+ reabsorption Aldosteron (discuss later)

bull K+ secretion Na+ - K+ - ATPase

bull H+ secretion Na+ -H+ antiport transport

bull NH3 secretion Related to H+ secretion

NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+

NH4Cl excretion with urine Na+ reabsorption into blood

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull DCT performs final adjustment of urine

bull Active secretion or absorption

bull Absorption of Na+ and Cl-

bull Secretion of K+ and H+ based on blood pH

bull Water is regulated by ADH (vasopressin)

bull Na+ K+ regulated by aldosterone

Secretion at the DCT

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

K+ and H+ secretion in distal tubule and collecting duct

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Co-transport of amino acids via Na+ symport mechanism

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Proximal tubule

Reabsorption Secretion

67 of filtered Na+ actively

reabsorbed not subject to control

Cl- follows passively

All filtered glucose and amino acids

reabsorbed by secondary active

transport not subject to control

65 of filtered H2O osmotically

reabsorbed not subject to control

Almost all filtered K+ reabsorbed

not subject to control

Variable H+ secretion

depending on acid-base

status of body

Distal tubule and collecting duct

Reabsorption Secretion

Variable Na+ reabsorbed by

Aldosterone

Cl- follows passively

Variable H2O reabsorption

controlled by vasopressin (ADH)

Variable H+ secretion

depending on acid-base

status of body

Variable K+ secretion

controlled by aldosterone

Table 8-2 Summary of transport across PT DT and collecting duct

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Urinary Concentration and Dilution

bull Hypertonic urine

Lack of water in body can forms concentrated urine

(1200 mOsmL)

bull Hypotonic urine

More water in body can forms dilute urine (50 mOsmL)

bull Isotonic urineInjury of renal function

bull Urinary dilution

The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water

bull Urinary concentration

The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

formation of dilute and concentrated urine

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Control of Urine Volume and Concentration

bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption

bull Precise control allowed via facultative water reabsorption

bull Osmolality

bull The number of solute particles dissolved in 1L of water

bull Reflects the solutionrsquos ability to cause osmosis

bull Body fluids are measured in milliosmols (mOsm)

bull The kidneys keep the solute load of body fluids constant at about 300 mOsm

bull This is accomplished by the countercurrent mechanism

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Formation of concentrated and diluted urine

Drink more water ADH water reabsorption

in DCT and CD diluted urine

Lack of water ADH water reabsorption

in DCT and CD concentrated urine

Role of the vasa recta for maintaining the

high solute concentration (NaCl and urea)

in the medullary interstitial fluid

Role of countercurrent exchanger

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Urinary concentrating environment

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Basic structure

ldquoUrdquotype of loop of Henle

Vasa rectarsquos cliper type (发卡样排列)

Collecting duct from cortex to medulla

bull Basic function

Different permeability of solutes and water in

DCT CD and loop of Henle

bull Osmotic gradient exit from cortex to medulla

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Tab8-2 Permeabilities of different segments of the renal tubule

Segments of

renal tubule

Permeability to

water

Permeability to

Na+

Permeability to

urea

Thick ascending

limb

Almost not Active transport of

Na+ Secondary

active Transport of Cl-

Almost not

Thin ascending

limb Almost not Yes Moderate

Thin descending

limb

Yes Almost not Almost not

Distal convoluted

tubule

Permeable

Under ADH

action

Secretion of K+

K+-Na+ exchange Almost not

Collecting

duct Permeable

Under ADH

action

Yes Cortex and outer

Medulla almost not

Inner medulla Yes

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Mechanisms for creating osmotic gradient in the

medullary interstitial fluid

Formation of osmotic gradient is related to

physiological characters of each part of renal tubule

Outer medulla

Water are permeated in descending thin limb but not NaCl

and urea

NaCl and urea are permeated in ascending thin limb but

not water

NaCl is active reabsorbed in ascending thick limb but not

Urea and water

Formation of osmotic gradient in outer medulla is

due to NaCl active reabsorption in outer medulla

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Inner medulla

bull High concentration urea exit in tubular fluid

bull Urea is permeated in CD of inner medulla but not

in cortex and outer medulla

bull NaCl is not permeated in descending thin limb

bull NaCl is permeated in ascending thin limb

bull Urea recycling

bull Urea is permeated in ascending thin limb part of urea into

ascending thin limb from medulla and then diffusion to

interstitial fluid again

bull Formation of osmotic gradient in inner medulla is

due to urea recycling and NaCl passive diffusion in inner

medulla

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Countercurrent Mechanism

bull Interaction between the flow of filtrate through the loop of Henle

(countercurrent multiplier) and the flow of blood through the vasa

recta blood vessels (countercurrent exchanger)

bull The solute concentration in the loop of Henle ranges from 300

mOsm to 1200 mOsm

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Countercurrent exchange Countercurrent exchange is a common process in

the vascular system Blood flows in opposite

directions along juxtaposed decending (arterial) and

ascending (venous) vasa recta and solutes and water

are Exchanged between these capillary blood vessels

Countercurrent multiplication Countercurrent multiplication is the process where

by a small gradient established at any level of the

loop of Henle is increased (maltiplied) into a much

larger gradient along the axis of the loop

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Loop of Henle Countercurrent Multiplication

bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid

bull Maintains the osmotic gradient

bull Delivers blood to the cells in the area

bull The descending loop relatively impermeable to solutes highly permeable to water

bull The ascending loop permeable to solutes impermeable to water

bull Collecting ducts in the deep medullary regions are permeable to urea

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Medullary osmotic gradient

bull H2OECFvasa recta vessels

Countercurrent Multiplier and Exchange

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Formation of Concentrated Urine

bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis

bull This equalizes the osmolality of the filtrate and the interstitial fluid

bull In the presence of ADH 99 of the water in filtrate is reabsorbed

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Formation of Dilute Urine

bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted

bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis

bull Collecting ducts remain impermeable to water no further water reabsorption occurs

bull Sodium and selected ions can be removed by active and passive mechanisms

bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Mechanism of ADH (Vasopressin) Action

Formation of Water Pores

bull ADH-dependent water reabsorption is called facultative

water reabsorption

Figure 20-6 The mechanism of action of vasopressin

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Water Balance Reflex

Regulators of Vasopressin Release

Figure 20-7 Factors affecting vasopressin release

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

bull Way of regulation for urine formation

Filtration Reabsorption and Secretion

bull Autoregulation

bull Solute concentration of tubular fluid

Osmotic diuresis -- diabaticmannitol

bull Glomerulotubular balance

Regulation of Urine Formation in the Kidney

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Nervous regulation

Role of Renal Sympathetic Nerve

Reflex of renal sympathetic nerve

Reflex of cardiopumonary receptor

renorenal reflex

Renin-angiotention-aldosterone system

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renin-Angiotension-Aldosterone System

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Regulation by ADH

bull Released by posterior

pituitary when

osmoreceptors detect

an increase in plasma

osmolality

bull Dehydration or excess

salt intake

bull Produces sensation

of thirst

bull Stimulates H20

reabsorption from

urine

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume

The regulation of ADH secretion

Source of ADH

Hypothalamus supraoptic and

paraventricular nuclei

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Source of ADH

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Figure 2615a b

Effects of ADH on the DCT and Collecting Ducts

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Regulation of ADH release over hydration

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Regulation of release hypertonicity

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Atrial Natriuretic Peptide Activity

Increase GFR reducing water reabsorption

Decrease the osmotic gradient of renal medulla and promotes Na+ excretion

Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney

Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Endothelin (ET)

Constriction blood vessels decrease GFR

Nitic Oxide (NO)

Dilation blood vessels increase GFR

Epinephrine (EP) Norepinephrine (NE)

promote Na+ and water reabsorption

Prostaglandin E2 I2

Dilation blood vessels excretion Na+ and water

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

A Summary of Renal Function

Figure 2616a

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

1 Concept

Renal clearance of any substance is the volume of

plasma that is completely cleaned of the substance by

the kidneys per unit time (min)

2 Calculate

concentration of it in urine timesurine volume

C =

concentration of it in plasma

Renal clearance

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Renal Clearance

RC = UVP

RC = renal clearance rate

U = concentration (mgml) of the substance in urine

V = flow rate of urine formation (mlmin)

P = concentration of the same substance in plasma

bull Renal clearance tests are used to

bull Determine the GFR

bull Detect glomerular damage

bull Follow the progress of diagnosed renal disease

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Theoretical significance of clearance

31 Measure GFR

bull A substance---freely filtered non reabsorbed

non secreted--its renal clearance = GFR

bull Clearance of inulin or creatinine can be used to

estimate GFR

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

32 Calculate RPF and RBF

A substance--freely filtered non reabsorbed secreted

completely from peritubular cells ---a certain

concentration in renal arteries and 0 in venous

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

33 Estimate of tubular handling for a substance

If the clearance of substancegt125mlmin

---it must be secreted

If it lt125mlmin --- it must be reabsorbed

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Physical Characteristics of Urine

Color and transparency

bull Clear pale to deep yellow (due to urochrome)

bull Concentrated urine has a deeper yellow color

bull Drugs vitamin supplements and diet can change the color of urine

bull Cloudy urine may indicate infection of the urinary tract

pH

bull Slightly acidic (pH 6) with a range of 45 to 80

bull Diet can alter pH

Specific gravity

bull Ranges from 1001 to 1035

bull Is dependent on solute concentration

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Chemical Composition of Urine

bull Urine is 95 water and 5 solutes

bull Nitrogenous wastes include urea uric acid and

creatinine

bull Other normal solutes include

bull Sodium potassium phosphate and sulfate ions

bull Calcium magnesium and bicarbonate ions

bull Abnormally high concentrations of any urinary

constituents may indicate pathology

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Urine Volume and Micturition

1 Urine volume

Normal volume 10~20Lday

Obligatory urine volume ~400mlday

Minimum needed to excrete metabolic wastes of

waste products in body

Oliguria--- urine volume lt 400mlday

Anuria---urine volume lt 100mlday

Accumulation of waste products in body

Polyuria--- urine volume gt 2500mlday long time

Abnormal urine volume Losing water and electrolytes

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Micturition

Functions of ureters and bladder

Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle

Urine is stored in bladder and intermittently ejected during urination or micturition

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Micturition

bull Micturition is process of emptying the urinary bladder

bull Two steps are involved

bull (1) bladder is filled progressively until its pressure rises

bull above a threshold level (400~500ml)

bull (2) a nervous reflex called micturition reflex occurs that empties bladder

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Micturition

bull Pressure-Volume curve of the bladder has

a characteristic shape

bull There is a long flat segment as the initial

increments of urine enter the bladder and

then a sudden sharp rise as the micturition

reflex is triggered

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Pressure-volume graph for normal human

bladder

100 200 300 400

025

050

075

100

125

1st desire

to empty

bladder

Discomfort Sense of

urgency

Volume (ml)

Pre

ss

ure

(k

Pa

)

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Micturition (Voiding or Urination)

bull Bladder can hold 250 - 400ml

bull Greater volumes stretch bladder walls initiates micturation reflex

bull Spinal reflex

bull Parasympathetic stimulation causes bladder to contract

bull Internal sphincter opens

bull External sphincter relaxes due to inhibition

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Innervation of bladder

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Urination Micturation reflex

Figure 19-18 The micturition reflex

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Micturition (Voiding or Urination)

Figure 2520a b

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Review Questions

Explain concepts

1Glomerular filtration rate

2 Effective filtration pressure

3 Filtration fraction

4Renal glucose threshold

5Osmotic diuresis

6Renal clearance

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Review Questions

1 What are the functions of the kidneys

2 Describe autoregulation of renal plasma flow

3 What are three basic processes for urine formation

4 Describe the forces affecting glomerular filtration

5 Describe the factors affecting GFR

6 What is the mechanism of sodium reabsorption in the proximal tubules

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria

Review Questions

7 What is the mechanism of hydrogen ion

secretion and bicarbonate reabsorption

8 What is the mechanism of formation of

concentrated and diluted urine

9 After drinking large amount of water what does

the amount of urine change Why

10 Why a patient with diabetes has glucosuria and

polyuria