Acids bases buffers and disorders by dr. ashok kumar j

- it donates proton
B– is an anion liberated by the deprotonation of
the acid
, so it is called conjugate
base
8/19/2014 2
Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry

8/19/2014 3Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry

Example Acid-Base Reactions

e.g. HCl ——> H+(aq) + Cl¯(aq)
HNO3 ——> H+(aq) + NO3¯(aq)
H2SO4 ——> 2H+(aq) + SO4
2-(aq)

2. Weak acids get dissociated partially
Conjugate 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

Equilibrium constant for ionization reaction is
called ionization or dissociation constants (Ka)

[B–]
pH pKa log10
[BH]
8/19/2014 11
Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry

value of pKa is lower for strong acids
and higher for weak acids

Mechanism of Buffer Action
Acetate buffer
CH3COO H / CH3COONa

Estimated by calculating the amount of
or required to change the pH of one
liter of buffer by one unit.

[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 pyrimidine
NH2 ---- = NH
C-OH ----- C=O

Normal pH of
blood
7.35 7.45
Average 7.4

Bicarbonate Buffer
Phosphate Buffer
Protein Buffer
Hemoglobin buffer
Ammonia buffer

• 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

• NaH2PO4 – is excreted in urine daily
- Normal excretion is 30mEq/L

CO2
Cl- Cl-
Plasma
Erythrocyte

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

HCO3
-HCO3
-
H2O + CO2 H2CO3
-
H+ H+
Tubular cell Tubular
Lumen
Na+
Na+

HCO3
-HCO3
-
H2O + CO2 H2CO3
-
H+ H+ HCO3
-+
H2CO3
-
H2OCO2 +CO2
Lumen

When there is an excess of acid production in
the body, H+ are excreted in urine as titrable
acid and ammonia

HCO3
-
H2O + CO2 H2CO3
-
H+
NH4
+
H+
Lumen
NH3
Titrable acid
Na2HPO4
-
NaH2PO4
-
GLUTAMIN
GLUTAMATE
Glutaminase NH3

Anion Gap
In Extracellular fluid
Sum 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 anions
Chloride 98mEq/L
Bicarbonate 25mEq/L
• Unmeasured anion
Protein 15mEq/L
Phosphate 2mEq/L
Organic acids 5mEq/L
Sulfate 1mEq/L

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

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]

[Bicarbonate]
[Carbonic acid]
pH pKa log10
Regulated by Kidney
Metabolic component
Decreased Bicarbonate
Decreases the ratio
Decreases pH
Increased Carbonic acid
Decreases the ratio
Decreases pH
Regulated by lungs
Respiratory component

[Bicarbonate]
[Carbonic acid]
pH pKa log10
Regulated by Kidney
Metabolic component
Increased Bicarbonate
Increases the ratio
Increases pH
Decreased Carbonic acid
Increases the ratio
Increases pH
Regulated by lungs
Respiratory component

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]

[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

1. Uncompensated
Compensatory mechanism has not
begun
2. Partially compensated
Compensatory mechanism has begun
pH is not yet normal
3. Fully compensated
Compensatory mechanism has
brought pH to normal

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

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”

Causes :
1. Increased production of organic acids
like acetoacetic acid , 3-OH butyric acid &
lactic acid
Diabetic ketoacidosis,
Starvation ketoacidosis,
Lactic acidosis

2. Salicylate intoxication
Generally occurs with blood salicylate level
above 30 mg/dl
Salicylate stimulates respiratory centre
3. Paraldehyde toxicity
Pathogenesis is ill defined ; Acidosis
may actually due to ketosis ; due to 3 OH
butyric acid as the main acid product

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

6. Tissue hypoxia – Anaerobic metabolism
- Accumulation of organic
acids
In all these conditions there is increased
anion gap

7. Loss of Na+, K+, & bicarbonate from
gastrointestinal tract ( as in diarrhoea)
Loss of bicarbonate is replaced by chloride
Results in hyperchloremic acidosis
8. Ureterosigmoidostomy
- Metabolic acidosis

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

10. Renal tubular acidosis
Loss of bicarbonate due to decreased
tubular secretion of H+
Type I or Distal renal tubular acidosis
Absorption of bicarbonate is
defective
pH of urine is >5.5
Compensatory 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

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

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

Uncompensated Metabolic acidosis
Partiallycompensated Metabolic acidosis
Compensated Metabolic acidosis
Fully
compensated
Partially
compensated
uncompensated
NormaldecreaseddecreasedpH
DecreaseddecreasednormalpCO2
DecreaseddecreaseddecreasedHCO3
pO2

Metabolic alkalosis
• Therapeutic administration of large dose of
alkali – chronic intake of excess antacids
- Intravenous administration of
bicarbonate

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

Weakness of respiratory muscles

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.

RENAL COMPENSATION
 Na-H+ exchange
 Ammonia formation
 Reclamation of HCO3

Fully
compensated
Partially
compensated
uncompensated
normaldecreaseddecreasedpH
increasedincreasedincreasedpCO2
increasedincreasednormalHCO3
pO2

Fully
compensated
Partially
compensated
uncompensated
NormalIncreasedIncreasedpH
DecreasedDecreasedDecreasedpCO2
DecreaseddecreasedNormalHCO3
pO2

 BUFFER SYSTEM
 RBC and tissue buffers provide H+ that
consumes HCO3
 RENAL COMPENSATION
 Decreased reclamation of HCO3

Thank you

Acids bases buffers and disorders by dr. ashok kumar j

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Acids bases buffers and disorders by dr. ashok kumar j