Prof.Dr. Ümmühan İşoğlu-Alkaç

İ.Ü. İstanbul Tıp Fakültesi Fizyoloji Anabilim Dalıalkac@istanbul.edu.tr

YU Medical Faculty, 09.10.2013

Microcirculation and Lymphatic System

Microcirculation and the

Lymphatic System

Structure of the microcirculation

and capillary system

• The arterioles are highly muscular …

• Metarterioles (the terminal arterioles) do not have a

continuous muscular coat, but smooth muscle fibers encircle

the vessel at intermittent points

• Precapillary sphincter between the metarteriole and capillary

• The venules are larger than the arterioles and have much

weaker muscular coat

• Local conditions of the tissues and regulation of blood flow

Structure of the microcirculation and

capillary system

Structure of the capillary wall

• Total thickness of the capillary wall is only about 0.5 µm, 500-900 m2 , 4-9 µm, funct.cell:20-30 µm

Special types of pores and certain organs

1) In the brain, junctions between the capillary endothelial

cells are mainly “tight” junctions that allow only

extremely small molecules such as water, O2, CO2 for

passage

2) In the liver, the opposite is true.

3) The pores of the gastrointestinal capillary membranes

are midway between those of the muscle and liver

4) In the glomerular structure of the kidney, there are small

oval windows on the capillary walls called “fenestrae”

(fenestrated capillaries)

Liver, Bone Marrow, Spleen

Flow of Blood in the Capillaries-

Vasomotion

• Blood usually does not flow continuously through the

capillaries

• It flows intermittently every few seconds or minutes

• This phenomenon is called “vasomotion”

• The most important factor to affect the degree of

openning and closing of the metarterioles and

precapillary sphincters is the oxygen concentration

• Average function of the capillary system…

Exchange of water, nutrients and other substances

between the blood and interstitial fluid

• Diffusion through the capillary membrane: the most

important means for transport of substances between the

plasma and interstitial fluid

• Lipid soluble substances can diffuse directly through the cell

membranes of the capillary endothelium (e.g. O2 and CO2)

• Water-soluble, non-lipid-soluble substances diffuse only

through intercellular pores in the capillary membrane (e.g.

water molecules, Na ions, Cl ions and glucose)

• Effect of concentration difference on net rate of diffusion through

the capillary membrane

Exchange of water, nutrients and other substances

between the blood and interstitial fluid

Effect of molecular size on passage through the pores

Substance Molecular Weight Permeability

Water 18 1.00

NaCl 58.5 0.96

Urea 60 0.8

Glucose 180 0.6

Sucrose 342 0.4

Inulin 5,000 0.2

Myoglobin 17,600 0.03

Hemoglobin 68,000 0.01

Albumin 69,000 0.001

The Interstitium and Interstitial Fluid

• Interstitium and interstitial fluid (12 lt, ~1/6¨, -2 --- -3 mmHg)

• Two major types of structures

– Collagen fiber bundles

– Proteoglycan filaments

• Proteoglycan filaments: 98% hyaluronic acid and 2% protein

• “Gel” in the interstitium: because of large number of

proteoglycan filaments, it is difficult for fluid to flow easily

through tissue gel

• Interstitial fluid is the same as plasma except it contains low

concentrations of proteins

• Formation of edema… (%1 free fluid)

The Interstitium and Interstitial Fluid

Fluid filtration, hydrostatic and oncotic pressures

• The hydrostatic pressure in the capillary tends to force

fluid and its dissolved substances through the

capillary pores into the interstitial spaces

• Conversely, colloid osmotic pressure (oncotic

pressure) of the plasma proteins tends to cause fluid

movement by osmosis from the interstitial spaces into

the blood

• This oncotic pressure prevents significant loss of fluid

volume from blood

• Lymphatic system and recovery of proteins from the

interstitial space

Fluid filtration, hydrostatic and oncotic pressures

• Starling Powers:

• The hydrostatic pressure

• Kolloid osmotic pressure

(oncotic pressure)

Four primary hydrostatic and colloid osmotic forces

determine fluid movement through the capillary membrane

1) Capillary hydrostatic pressure (Pc)

2) Interstitial fluid (hydrostatic) pressure (Pif)

3) The capillary plasma colloid osmotic (oncotic)

pressure

4) Interstitial fluid colloid osmotic (oncotic) pressure

Net filtration pressure

• The net filtration pressure is positive, under

normal conditions

Capillary and Interstitial Hydrostatic Pressures

• Capillary hydrostatic pressure:

– Arterial end of capillary: 30 mmHg

– Venous end of capillary: 10 mmHg

• Interstitial fluid (hydrostatic) pressure:

• The true interstitial fluid pressure is negative,

averaging about -3 mmHg

• Pumping by the lymphatic system is the basic

cause of negative interstitial pressure

Plasma Colloid Osmotic (Oncotic) Pressure

• Proteins in the plasma cause oncotic pressure

– Non-permeability of plasma proteins

• Normal values: plasma oncotic pressure of normal

human plasma is about 28 mmHg

• 19 mmHg of this is caused by molecular effects of

dissolved proteins and 9 mmHg by Donnan effect (i.e.

Osmotic pressure caused by Na, K and other cations

held in the plasma by proteins)

• About 80% of plasma oncotic pressure results from

Albumin, 20% from globulin and almost none from

fibrinogen

Interstitial Fluid Colloid Osmotic (Oncotic)

Pressure

• Although size of the usual capillary pore is smaller

than the molecular sizes of the plasma proteins, this

is not true for all pores. Therefore, small amounts of

proteins leak into the interstitial space

• Presence of these proteins cause interstitial fluid

oncotic pressure (8 mmHg)

Exchange of Fluid Volume Through the

Capillary membrane

• The average capillary pressure at the arterial ends of

the capillaries is 15 to 25 mmHg greater than at the

venous ends.

• Because of this difference, fluid filters out of the

capillaries at the arterial end, but it is reabsorbed at

the venous end.

Analysis of the forces causing filtration at the arterial end of the capillary

Forces tending to move fluid outward:  

  Capillary pressure (arterial end of capillary) 30

  Negative interstitial free fluid pressure 3

  Interstitial fluid colloid osmotic pressure 8

    total outward force 41

Forces tending to move fluid inward:  

  Plasma colloid osmotic pressure 28

Summation of forces:  

  Outward 41

  Inward 28

    net outward force (at arterial end) 13

Analysis of reabsorption at the venous end of the capillary

Forces tending to move fluid inward:  

  Plasma colloid osmotic pressure 28

    total inward force 28

Forces tending to move fluid outward:  

  Capillary pressure (venous end of capillary) 10

  Negative interstitial free fluid pressure 3

  Interstitial fluid colloid osmotic pressure 8

    total outward force 21

Summation of forces:  

  Inward 28

  Outward 21

    net inward force 7

Starling Equlibrium for Capillary Exchange

Mean forces tending to move fluid outward:  

  Mean capillary pressure 17.3

  Negative interstitial free fluid pressure 3.0

  Interstitial fluid colloid osmotic pressure 8.0

    total outward force 28.3

Mean force tending to move fluid inward:  

  Plasma colloid osmotic pressure 28.0

    total inward force 28.0

Summation of mean forces:  

  Outward 28.3

  Inward 28.0

    net outward force 0.3

Net Filtration

• Outward forces: 28.3 mmHg

• Inward forces: 28 mmHg

• This slight excess of filtration is called net filtration: 0.3 mmHg

• 2 ml / min in the body

• Abnormal imbalance of forces at the capillary membrane

• If the mean capillary pressure rises above 17 mmHg, the net

force increases.

• As a result fluid will accumulate in the interstitial space and

edema will result.

• Conversely, if the capillary pressure falls very low, net

reabsorption of fluid will occur and blood volume will

increase…

arterial end

venous end

Vasodilatator theory

• According to this theory, greater the rate of

metabolism or the less the availability of oxygen or

some other nutrients to the tissue, the greater the

rate of formation of vasodilatator substances

• Adenosine, CO2, adenosine phosphate compounds,

histamine, K ions and H ions

• Importance of adenosine in local vasodilatation

Oxygen lack theory for local blood flow control

• Vasomotion, metarteriole and precapillary sphincter

• Smooth muscle requires oxygen to remain contracted

Lymphatic System

• Consists of two semi-independent parts

– A meandering network of lymphatic vessels

– Lymphoid tissues and organs scattered

throughout the body

• Returns interstitial fluid and leaked plasma

proteins back to the blood

• Lymph – interstitial fluid once it has entered

lymphatic vessels

Lymphatic System: Overview

Lymphatic System

• Exceptions for the lymphatic system:

superficial portions of the skin, central

nervous system, endomyosium of muscles

and bones.

• But even these tissues have prelymphatics

through which interstitial fluid can flow

• Lymph vessels from lower parts of the

body – Thoracic Duct

Lymphatic System

• Lymph from the left side of the head, left

arm, and parts of the chest also goes into

thoracic duct

• Lymph from right side of the head, right

arm, and parts of the thorax enters the

right lymph duct which empties into the

venous blood at the right side (juncture of

jugular vein and right subclavian vein)

Lymphatic System: Overview

Lymphatic Capillaries

• Similar to blood capillaries, with modifications– Remarkably permeable– Loosely joined endothelial minivalves– Withstand interstitial pressure and remain open

• The minivalves function as one-way gates that:– Allow interstitial fluid to enter lymph capillaries– Do not allow lymph to escape from the capillaries

Lymphatic Capillaries

* Total quantity of lymph is normally only 2-3 liters/day

* This lymph is continually absorbed from the tissues by

lymphatic capillaries and returned to the blood circulation

Lymphatic Vessels

• A one-way system in which lymph flows toward the heart

• Lymph vessels include:– Microscopic, permeable, blind-ended

capillaries– Lymphatic collecting vessels– Trunks and ducts

Lymphatic Capillaries

• During inflammation, lymph capillaries can absorb:

– Cell debris

– Pathogens

– Cancer cells

• Cells in the lymph nodes:

– Cleanse and “examine” this debris

• Lacteals – specialized lymph capillaries present in

intestinal mucosa

– Absorb digested fat and deliver chyle to the blood

Rate of Lymph Flow

• Any factor increasing

interstitial fluid pressure

also increases lymph flow.

Such factors include

– Elevated capillary

pressure

– Decreased plasma colloid

osmotic pressure

– Increased interstitial fluid

colloid osmotic pressure

– Increased permeability of

the capillaries

• Maximum lymph flow rate

Lymphatic Pump

• Intrinsic intermittent contraction of the lymph vessel walls

• External factors:

– Contraction of surrounding skeletal muscles

– Movement of parts of the body

– Pulsations of arteries adjacent to the lymphatics

– Compression of the tissues by objects outside the body

• The lymphatic pump becomes very active during exercise

Lymph Transport

• The lymphatic system lacks an organ that acts as a pump

• Vessels are low-pressure conduits

• Uses the same methods as veins to propel lymph– Pulsations of nearby arteries– Contractions of smooth muscle in the walls of

the lymphatics

www.youtube.com/watch?v=Kh-XdNnTZUo&feature=related

Lymphatic Pump

• Primary factors that determine the lymph flow:

– Interstitial fluid pressure

– Activity of the lymphatic pump

Interstitial Protein Concentration, Fluid Volume and Pressure

• The lymphatic system plays an important role in controlling

– protein concentrations in the interstitial fluid

– volume of interstitial fluid

– interstitial fluid pressure

• Significance of negative interstitial fluid pressure as a means for

holding the body tissues together

– Different tissues of the body are held together by connective

tissue fibers

– Skin sliding over the back of the hand and face

– It acts partially as a vacuum pump

– In its absence, edema develops.

Lymph Nodes

• Their two basic functions are:

– Filtration – macrophages destroy

microorganisms and debris

– Immune system activation – monitor for

antigens and mount an attack against them

Structure of a Lymph Node

http://trc.ucdavis.edu/biosci10v/bis10v/media/ch23/human_lymphatic.html