酸碱平衡及紊乱Acid – Base Balance

and Disturbances

Acid-Base BalanceMaintenance of the H+ concentration

in body fluid in a normal range H+ mol/L pH

Extracellular fluid Arterial blood 4.0 x 10-8 7.40 ± 0.05Venous blood 4.5 x 10-8 7.35 Interstitial fluid 4.5 x 10-8 7.35Intracellular fluid 1.0 x 10-6 6.0 to 4.0 x 10-8 7.4pH = - lg H+

Why is the acid - base balance important for life ?

Acid generation

•Volatile acid

CO2 + H2O H2CO3 H+ + HCO3-

H+ 15 –20 mol /d

• Fixed acids

phosphoric, sulfuric, lactic, ketone bodies etc.

H+ < 0.05 –0.10 mol /d

Regulation of acid – base balance

•Buffering Buffer system can bind and release H+

Dissociated buffer + H+ H undissociated buffer

Principal buffers in blood:

in Plasma in RBC

H2CO3 / HCO3- 35% 18%

HHb / Hb- 35%

HProt / Prot- 7%

H2PO4- / HPO4

2- 5%

Bicarbonate buffer system determines the pH of blood plasmaCO2 + H2O H2CO3 H+ + HCO3

-

Handerson-Hasselbalch Equation +

pH = pK + lg HCO3- / H2CO3 Na+

= 6.1 + lg HCO3- / 0.03 x PCO2

= 6.1 + lg 24 / 1.2 = 7.4

• Bicarbonate-carbonic acid system is the major extracellular buffer 53%

• H2CO3 can be regulated by lung• HCO3

- can be regulated by kidney

•Respiratory regulation

PaCO2, pH Chemorecertor Pulmonary ventilation PaCO2

pH 7.0 VA increases by 4-5 times pH VA decreases less

•Renal regulation Plasma pH

HCO3- H+

Reabsorption & Excretion Regeneration

Plasma pH

Renal H+ excretion = fixed acid production = 1mmol/kg/d

Reabsorption of HCO3- in different segments

of renal tubule

Reabsorption of HCO3- coupled with

H+ excretion in proximal tubules

CANa+

Regeneration

Regeneration of HCO3- coupled with the buffering

of secreted H+ by filtered Na2HPO4 in distal tubules

Cl-

ATP

Regeneration of HCO3- coupled with

buffering of H+ by NH3 in proximal tubular cells

Glutamine Tubular

lumen

glutaminase

NH3 NH3

-keto glutaric acid

NH4+ NH4

+

H2CO3 Na+

Na+

HCO3- H+ H+

ATP

Regeneration of HCO3- coupled with buffering

of H+ by NH3 in collecting tubular cells

Cl-

Net acid excretion by kidney

= NH4+ excretion + urinary titratable acid

– bicarbonate excretion

= nonvolatile acid production

In acidosis, a net addition of HCO3- back to blo

od as more NH4+ and urinary titratable acid are

excreted

In alkalosis, titratable acid and NH4+ excretion d

rop to 0, whereas HCO3- excretion increases

(No new bicarbonate is generated)

Parameters of acid – base balance

1.pH = 6.1 + lg HCO3-/ H2CO3

Normal value of pH in arterial blood 7.4±0.05

pH normal, may be

1) acid-base balance

2) compensatory acid-base disorder

3) mixed acid-base disorder

2. PaCO2 x 0.03 = H2CO3

Normal PaCO2 40 ± 6 mmHg

determined by the rate of CO2 elimination (alveolar ventilation), not by its production.

--- Respiratory parameter

3. Bicarbonate ( HCO3- )

Normal value of HCO3- in plasma under actual

condition is 24 ± 2 mmol/L

HA + NaHCO3 NaA + H2CO3

determined by the amount of nonvolatile acid produced in metabolism

--- Metabolic parameter

4. Anion gap (AG) = UA - UC

Na+

(140)

HCO3-

(24)

Cl-

(104)

UC(11)

UA(23)

mEq/L

= Na+ - ( HCO3-+Cl- )

= 140 - ( 24+104 )

= 12±2mEq/L

dAG =dUA = dHCO3-

Summary•The maintenance of H+ concentration of body fluid in a normal range is very important for life.

•Normal value of arterial pH is 7.35 – 7.45,

which is determined by the HCO3-/H2CO3 ratio, a

nd regulated by buffering, lung and renal regulation.

•Buffers act to minimize changes in pH induced by acid or base load; PaCO2 is controlled by alteration of pulmonary ventilation; HCO3

- in plasma is regulated by renal reabsorption and regeneration of HCO3

- coupled with equivalent H+ excretion.

Simple acid-base disorders

Metabolic acidosis

Primary decrease in plasma HCO3-

Causes of metabolic acidosis:

• High AG type ---- Fixed acid HCO3-

1. Production of fixed acids

2. Retention of fixed acids --- GFR

3. Acid intake – salicylate etc.

• Normal AG type ---- hyperchloremic

1. HCO3- reabsorption or regeneratio

n in renal tubules: Renal tubular acidosis ( RTA ) Renal failure Carbonic anhydrase inhibitor

2. HCO3- losses in alimentary tract:

Diarrhea

3. HCl, NH4Cl intake 4. Hyperkalemia

§ Hyperchloremia in normal AG type due to reabsorption of Cl-

RTA HCO3- reabsorption

Cl-reabsorption Diarrhea Ald NaCl reabsorption

§ Paradoxical alkaluria in acidosis Renal tubular acidosis ---

HCO3- reabsorption or H+ excretion

Hyperkalemia renal H+ excretion

Compensation of metabolic acidosis:

1) Extracellular buffering --- immediately

HA + NaHCO3 NaA + H2CO3

2) Respiratory compensation

Ventilation in few min, maximal in 12-24 h

d PaCO2 = 1.2 d HCO3- ± 2

3) Intracellular buffering --- in 2-4h

4) Renal compensation

begin in several h, maximal in 3-5d

Respiratory acidosis Primary increase of PaCO2

Causes:

1) External respiratory dysfunction

2) PCO2 in inspired air

Compensation of respiratory acidosis

1. Buffering ---- immediately

CO2 H2O

H2CO3

HCO3-

HHb

KHb

K+ K+

H+

H2CO3

HCO3-HCO3

-

Cl-

2. Renal compensation

Acute --- d [ HCO3-] = 0.1 d PaCO2 ± 1.5

Chronic ---d [HCO3-] = 0.4 d PaCO2 ± 3

Pathophysiological changes caused by acidosis

• Cardiovascular system

1) Decrease of myocardial contractility – pH<7.2 Responsiveness of -adrenoceptor

Contraction

Ca2+influx

SR [Ca2+]i↑

Binding to Troponin

H+

2) Cardiac arrhythmia

Acidosis hyperkalemia arrhythmia

3) Vasodilation

Responsiveness of -adrenoreceptor

•Central nervous system depression, coma ( pH < 6.9 ) 1) GABA ---- glutamate decarboxylase activity

2) Oxidase activity ATP 3) Cerebral vasodilation intracranial pressure

What kind of acidosis has more effect on CNS, metabolic or respiratory?

H+ (-)

Na+ Na+ AldAld ATPase [K+]e K+channel K+ K+ [K+]e H+ (-)

Mg2+(-)

Urine flow K+

• Hyperkalemia --- 1) [H+]e exchange for [K+]i

2) Decreased excretion of K+ by distal renal tubules

Tubular l Principal cell Interstitial fluid

Metabolic alkalosis Primary increase of HCO3

-

Causes:

1) Excess bicarbonate load ---- intake

2) Gastric H+ loss ---- vomiting

Why HCO3- in plasma is increased?

3) Renal H+ loss

Diuretics --- distal urine flow

Hyperaldosteronism ---

activation of H+ pump and Na+-K+ pump

4) Hypokalemia

Compensation of metabolic alkalosis

1) Buffering --- in cells

2) Respiratory compensation ---incomplete

3) Renal compensation --- tremendous

•The causes of paradoxical aciduria?

•What kind of metabolic alkalosis is saline responsive? or saline resistant?

vomiting? diuretics?

primary hyperaldosteronism?

Respiratory alkalosis

Primary decrease of PaCO2

• Cause ---- alveolar hyperventilation

Hypoxia, psychoneurosis, fever etc.

• Compensation

Buffering

Renal compensation

Acute -----dHCO3 = 0.2 d PaCO2 2.5

Chronic ---dHCO3 = 0.5 d PaCO2 2.5

Functional and Metabolic Changes caused by alkalosis

•Central nervous system Dysphoria, confusion, seizure, coma etc.

1) GABA

2) Hypoxia from:

hypoventilation, cerebral vasoconstriction

left-shift of oxyhemoglobin dissociation curve

• Neuromuscular excitability ---- cramping

ionic calcium in plasma

• Hypokalemia --- paresis, arryhthmia

Analysis of simple acid-base disorder

Mixed acid-base disorders

•Double acid base disorders

Metabolic Metabolic

acidosis alkalosis

Respiratory Respiratory

acidosis alkalosis

•COPDO2HCO3- PaCO2 pH

CO2PaCO2 HCO3- pH

HCO3-/ PaCO2 pH

• COPD + O2 PaCO2 HCO3- pH

+ Diuretics HCO3- PaCO2 pH

HCO3- / PaCO2 pH normal

•Renal failure HCO3- PaCO2 pH

Vomiting HCO3- PaCO2 pH

N HCO3- / N PaCO2 pH normal

All these parameters are normal,

how to find out the acid-base disorder?

•Triple acid-base disorders

Metabolic Metabolic

acidosis alkalosis

Respiratory Respiratory

acidosis alkalosis

Exp:

COPD O2 HCO3- PaCO2 pH

CO2 PaCO2 HCO3 pH

Diuretics HCO3- PaCO2 pH

HCO3- PaCO2 pH

Summery

•Metabolic acidosis is induced by primary decrease of HCO-

3 owing to increased production or retention of fixed acides or HCO-

3 loss.

•Metabolic alkalosis is induced by primary increase of HCO-

3 due to H+ loss.

•Respiratory acidosis or alkalosis is induced by primary increase or decrease of CO2 caused by hypoventilation or hyperventilation.

•Acidosis depresses activity of CNS and myocardial contractility, and induces cardiac arrhythmia and vasodilation.

•Alkalosis results in dysfunction of CNS and cramping.

•Different kinds of acid-base disorders may coexist in patients.