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???????Acid Base Balance and Disturbances

• Pathophysiology Department, Tongji Medical
  College, HUST

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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 0.05
• Venous blood 4.5 x 10-8 7.35
  
• Interstitial fluid 4.5 x 10-8
  7.35
• Intracellular fluid 1.0 x 10-6
  6.0
• to 4.0 x 10-8
  7.4
• pH - lg ?H?

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Why is the acid - base balance important for
life ?
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Acid generation

• Volatile acid
• CO2 H2O ? H2CO3 ? H HCO3-
• H 15 20 mol /d
• Fixed acids
• phosphoric, sulfuric, lactic, ketone bodies
  etc.
• H lt 0.05 0.10 mol /d

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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- / HPO42-
  5

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Bicarbonate buffer system determines the pH of
blood plasma

• CO2 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
  
  
• 
  
  
  
  

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• Respiratory regulation
• ?PaCO2, ?pH
• ?
• Chemorecertor
• ?
• ? Pulmonary ventilation
• ?
• ?PaCO2
• pH 7.0 ? VA increases by 4-5 times
• ?pH ? VA decreases less

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• Renal regulation
• ?Plasma pH
• ?HCO3- ? H
• Reabsorption Excretion
• Regeneration
• ?Plasma pH
• Renal H excretion fixed acid production
  1mmol/kg/d

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Reabsorption of HCO3- in different segments of
renal tubule
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Reabsorption of HCO3- coupled with H excretion
in proximal tubules
Na
CA
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Regeneration
Regeneration of HCO3- coupled with the
buffering of secreted H by filtered Na2HPO4 in
distal tubules
ATP
Cl-
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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
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Regeneration of HCO3- coupled with buffering of
H by NH3 in collecting tubular cells
Cl-
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• Net acid excretion by kidney
• NH4 excretion urinary titratable acid
• bicarbonate excretion
• nonvolatile acid production
• In acidosis, a net addition of HCO3- back to
  blood as more NH4 and urinary titratable acid
  are excreted
• In alkalosis, titratable acid and NH4 excretion
  drop to 0, whereas HCO3- excretion increases
• (No new bicarbonate is generated)

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Parameters of acid base balance

• pH 6.1 lg HCO3-/ H2CO3
• Normal value of pH in arterial
  blood 7.40.05
• pH normal, may be
• 1) acid-base balance
• 2) compensatory acid-base disorder
• 3) mixed acid-base disorder

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• 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

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4. Anion gap (AG) UA - UC
Na - ( HCO3-Cl- ) 140 - ( 24104 )
122mEq/L ?dAG ?dUA ?dHCO3-
Cl- (104)
Na (140)
HCO3- (24)
UA (23)
UC
(11)
mEq/L
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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,
  and 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.

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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.

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• Normal AG type ---- hyperchloremic
• 1. ?HCO3- reabsorption or regeneration 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

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• 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

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• 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

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• Respiratory acidosis
• Primary increase of PaCO2
• Causes
• 1) External respiratory dysfunction
• 2) ?PCO2 in inspired air

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• Compensation of respiratory acidosis
• 1. Buffering ---- immediately

CO2
H2O
H2CO3
H2CO3
K
HCO3-
H
HCO3-
HCO3-
Cl-
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• 2. Renal compensation
• Acute --- d HCO3- 0.1 d PaCO2 1.5
• Chronic ---d HCO3- 0.4 d PaCO2 3

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• Pathophysiological changes caused by acidosis
• Cardiovascular system
• 1) Decrease of myocardial contractility
  pHlt7.2 ?Responsiveness of ?-adrenoceptor

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• 2) Cardiac arrhythmia
• Acidosis ? hyperkalemia ? arrhythmia
• 3) Vasodilation
• ? Responsiveness of ?-adrenoreceptor

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• Central nervous system
• depression, coma ( pH lt 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?

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• Hyperkalemia --- 1) He exchange for Ki
• 2) Decreased excretion of K by distal renal
  tubules

H
(-) Na Na
Ald Ald
ATPase Ke
Kchannel K K
Ke H (-)

Mg2(-) Urine flow
K

Tubular l Principal cell Interstitial
fluid
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• 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

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• Compensation of metabolic alkalosis
• 1) Buffering --- in cells
• 2) Respiratory compensation ---incomplete
• 3) Renal compensation --- tremendous

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• The causes of paradoxical aciduria?
• What kind of metabolic alkalosis is saline
  responsive? or saline resistant?
• vomiting? diuretics?
• primary hyperaldosteronism?

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• 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

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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

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Analysis of simple acid-base disorder
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Mixed acid-base disorders

• Double acid base disorders
• Metabolic Metabolic
• acidosis
  alkalosis
• Respiratory Respiratory
• acidosis
  alkalosis

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• COPD??O2???HCO3- ? ?PaCO2 ?pH
• ?CO2???PaCO2 ??HCO3- ?pH
• ? HCO3-/ ? PaCO2 ? ?
  ?pH
• COPD O2 ???PaCO2 ??HCO3- ?pH
• Diuretics ? ??HCO3- ??PaCO2 ?pH
• ? ?? HCO3- / ?? ?PaCO2 ? pH normal

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• 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?

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• Triple acid-base disorders
• Metabolic
  Metabolic
• acidosis
  alkalosis
• Respiratory
  Respiratory
• acidosis
  alkalosis

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• Exp
• COPD ? ?O2? ??HCO3- ? ?PaCO2 ? pH
• ?CO2? ??PaCO2 ? ?HCO3 ? pH
• Diuretics ? ?? HCO3- ?? PaCO2 ? pH
• ?HCO3- ??PaCO2 ?
  ? pH

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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.

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• 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.