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- it donates proton B– is an anion liberated by the deprotonation of
the acid, so it is called conjugate
base8/19/2014 2
Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 3Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
Example Acid-Base Reactions
8/19/2014 4Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 5Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
e.g. HCl ——> H+(aq) + Cl¯(aq)
HNO3——> H
+(aq) + NO
3¯(aq)
H2SO
4——> 2H
+(aq) + SO
4
2-(aq)
8/19/2014 6Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
2. Weak acids get dissociated partiallyConjugate bases of these acids are strong (have greater affinity for proton).e.g.: acetic acid
CH3COO-(aq) + H+(aq)
Carbonic acid is a weak acid – formed by hydration of carbon dioxide
8/19/2014 7Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 8Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
Equilibrium constant for ionization reaction iscalled ionization or dissociation constants (Ka)
8/19/2014 9Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 10Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
[B–]pH pKa log10
[BH]
8/19/2014 11Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
value of pKa is lower for strong acids and higher for weak acids
8/19/2014 12Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 13Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
Mechanism of Buffer Action
Acetate bufferCH3COO H / CH3COONa
8/19/2014 14Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 15Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
Estimated by calculating the amount of
or required to change the pH of one
liter of buffer by one unit.
8/19/2014 16Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 17Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 18Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
[Base]pH pKa log10
[Acid]
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 19
Significance of pH
1. Isoelectric pH
2. Optimum pH
3. Tautomeric forms of purine and pyrimidineNH2 ---- = NHC-OH ----- C=O
Normal pH of
blood
7.35 7.45
Average 7.4
8/19/2014 20Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 21Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 22Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 23Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
Bicarbonate BufferPhosphate BufferProtein BufferHemoglobin bufferAmmonia buffer
8/19/2014 24Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 25Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 26Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
• Normal pCO2 of arterial blood is 40 mmof Hg• Normal carbonic acid concentration is 1.2 mmol/L• pKa of carbonic acid is 6.1
[Bicarbonate]pH pKa log10
[Carbonic acid]
[24]pH log10
[1.2]
pH log10 20
pH
pH
8/19/2014 27Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 28Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
8/19/2014 29Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
• NaH2PO4 – is excreted in urine daily- Normal excretion is 30mEq/L
8/19/2014 30Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
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CO2
Cl- Cl-
PlasmaErythrocyte
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 37
Kidney plays a major role in acid-base regulation
2. Reclaimation the bicarbonate ions present in the ultrafiltrate
1. Excretion of H+
3. Excretion of titrable acid and ammonia
4. Excretion of ammonia
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 38
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 39
HCO3-HCO3
-
H2O + CO2 H2CO3-
H+ H+
Tubular cell Tubular Lumen
Na+Na+
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 40
HCO3-HCO3
-
H2O + CO2 H2CO3-
H+ H+ HCO3-+
H2CO3-
H2OCO2 +CO2
Tubular cell Tubular Lumen
8/19/2014 41Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry
When there is an excess of acid production in the body, H+ are excreted in urine as titrableacid and ammonia
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 42
HCO3-
H2O + CO2 H2CO3-
H+
NH4+
H+
Tubular cell Tubular Lumen
NH3
Titrable acid
Na2HPO4-
NaH2PO4-
GLUTAMIN
GLUTAMATE
Glutaminase NH3
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 43
Anion Gap
In Extracellular fluidSum of anions = Sum of cations
- Electrical neutrality
•Sodium (Na+) and Potassium (K+) together accounts for 95% of the cations
•Chloride and bicarbonate accounts for only 86% of the anions
•Theses are the electrolytes commonly measured
• Measured cations
Sodium 136 mEq/L
Potassium 4 mEq/L
• Unmeasured Cation
Calcium 4.5 mEq/L
Magnesium 1.5 mEq/L
• Measured anionsChloride 98mEq/LBicarbonate 25mEq/L
• Unmeasured anionProtein 15mEq/LPhosphate 2mEq/LOrganic acids 5mEq/LSulfate 1mEq/L
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 44
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 45
Unmeasured anions constitute the anion gap
Calculated as difference between measured cations and measured anions
Anion Gap = (Na+ + K+) - (Cl- + HCO3-)
= ( 140 + 4) – (103 + 25)= 16
Normal is about 12 mEq/L
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 46
Acidosis : Clinical state where acids accumulate or bases are lost
Alkaosis : Clinical state where accumulation of base or loss of acids
[Bicarbonate]pH pKa log10
[Carbonic acid]
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 47
[Bicarbonate][Carbonic acid]
pH pKa log10
Regulated by KidneyMetabolic component
Decreased BicarbonateDecreases the ratioDecreases pH
Increased Carbonic acidDecreases the ratioDecreases pH
Regulated by lungsRespiratory component
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 48
[Bicarbonate][Carbonic acid]
pH pKa log10
Regulated by KidneyMetabolic component
Increased BicarbonateIncreases the ratioIncreases pH
Decreased Carbonic acidIncreases the ratioIncreases pH
Regulated by lungsRespiratory component
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 49
1. Metabolic acidosis :- Primary alkali deficit
2. Metabolic acidosis :- Primary alkali excess
3. Respiratory acidosis :- Primary carbonic acid excess
4. Respiratory alkalosis :- Primary carbonic acid deficit
pH pKa log10[Bicarbonate][Carbonic acid]
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 50
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 51
[Bicarbonate]pH pKa log10
[Carbonic acid]
• Acid base disturbances will be followed by compensatory change in counteracting variable
e.g
a. Primary change in bicarbonate involves alteration in pCO2
b. Primary increase in arterial pCO2 involves an increase in arterial bicarbonate
• Compensatory changes try to restore the pH normal
• Compensatory changes cannot fully correct a disturbance
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 52
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 53
1. UncompensatedCompensatory mechanism has not begun
2. Partially compensatedCompensatory mechanism has begun pH is not yet normal
3. Fully compensatedCompensatory mechanism has brought pH to normal
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 54
Increased production of hydrogen ions
Impaired excretion of hydrogen ions
Loss of bicarbonate from the gastrointestinal tract or in urine
Ingestion of hydrogen ions or drugs which are metabolized to acids
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 55
Production of organic acids exceeds the rate of elimination
Acidosis may be accompanied by loss of cations, that are excreted with anions
Acids are nutralized by alkali – bicarbonate concentration decreases
“Primary alkali deficit”
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 56
Causes :1. Increased production of organic acids
like acetoacetic acid , 3-OH butyric acid & lactic acid
Diabetic ketoacidosis, Starvation ketoacidosis,Lactic acidosis
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 57
2. Salicylate intoxicationGenerally occurs with blood salicylate level above 30 mg/dl
Salicylate stimulates respiratory centre
3. Paraldehyde toxicityPathogenesis is ill defined ; Acidosis
may actually due to ketosis ; due to 3 OH butyric acid as the main acid product
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 58
4. Isoniazide – is antimicobacterial agent- may be hepatotoxic- significant liver damage- impairs clearance of lactate
5. Iron toxicity – production of toxic peroxides- Mitochondrial poison- Interferes with normal cellular
respiration- Lactate is formed
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 59
6. Tissue hypoxia – Anaerobic metabolism- Accumulation of organic
acids
In all these conditions there is increased anion gap
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 60
7. Loss of Na+, K+, & bicarbonate from gastrointestinal tract ( as in diarrhoea)
Loss of bicarbonate is replaced by chlorideResults in hyperchloremic acidosis
8. Ureterosigmoidostomy- Metabolic acidosis
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 61
8. Acidosis can be due to administration of ammonium chloride, lysine, argininehydrochloride – due to formation of HCl
9. Aldosteron stimulates distal tubular acid and potassium secretion
In hyporaldosteronism loss of this effect leads to metabolic acidosis
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 62
10. Renal tubular acidosisLoss of bicarbonate due to decreased tubular secretion of H+
Type I or Distal renal tubular acidosisAbsorption of bicarbonate is
defectivepH of urine is >5.5Compensatory increase in
chloride (Hyperchloremic acidosis)
• Type II or proximal renal tubular acidosis
Secretion of hydrogen ions is defective
pH of urine is < 5.5
Potassium is normal
Type IV due to resistance to aldosterone
pH <5.5
Hyperkalemia
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 63
BUFFER SYSTEM
Mainly HCO3/ carbonic acid minimizes change in pH
HCO3 concentration is decreased and ratio of HCO3/H2 CO3 less
than 20/1
RESPIRATORY MECHANISM
Increases rate and depth of respiration (Kussumauls breathing)
Elimination of carbonic acid as CO2 ,
Decrease in pCO2 and consequently decrease in H2 CO3
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 65
RENAL MECHANISM
Increases excretion of acid and preserves the base
by increased rate of Na- H exchange
Increases ammonia formation and increased
reabsorption of HCO3
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 66
Uncompensated Metabolic acidosisPartiallycompensated Metabolic acidosisCompensated Metabolic acidosis
Fully compensated
Partially compensated
uncompensated
NormaldecreaseddecreasedpH
DecreaseddecreasednormalpCO2
DecreaseddecreaseddecreasedHCO3
pO2
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 67
Metabolic alkalosis
• Therapeutic administration of large dose of alkali – chronic intake of excess antacids
- Intravenous administration of bicarbonate
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 68
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 69
RESPIRATORY MECHANISM:
Increase in pH depresses the respiratory center,
causes retention of CO 2 which in turn increases the
H 2CO 3 .
RENAL MECHANISM:
Kidney decreases Na –H+ exchange,
decreases the formation of ammonia
decreases reclamation of bicarbonate.
Fully compensated
Partially compensated
uncompensated
normalincreasedincreasedpH
increasedincreasednormalpCO2
increasedincreasedincreasedHCO3
pO2
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Weakness of respiratory muscles
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 73
BUFFER SYSTEM
Excess carbonic acid is buffered with haemoglobin and
protein buffer
RESPIRATORY MECHANISM
Increase in pCO2 stimulates respiratory center
Increase in rate and depth of respiration provided the
defect is not in respiratory center.
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 74
RENAL COMPENSATION
Na-H+ exchange
Ammonia formation
Reclamation of HCO3
Fully compensated
Partially compensated
uncompensated
normaldecreaseddecreasedpH
increasedincreasedincreasedpCO2
increasedincreasednormalHCO3
pO2
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 75
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 76
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 77
Fully compensated
Partially compensated
uncompensated
NormalIncreased IncreasedpH
DecreasedDecreasedDecreasedpCO2
DecreaseddecreasedNormalHCO3
pO2
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 78
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 79
BUFFER SYSTEM
RBC and tissue buffers provide H+ that
consumes HCO3
RENAL COMPENSATION
Decreased reclamation of HCO3
Thank you
8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 80