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Maintenance of pH of Body - Physiology Short Notes

Normal Blood pH

• Arterial blood pH is maintained between 7.35 and 7.45 (normal = 7.40)
• Intracellular pH ranges from 7.0 to 7.3
• pH = -log[H+]; a 10-fold change in [H+] = a shift of 1 pH unit
• Even small pH changes alter enzyme activity, protein conformation, ion channel function, and receptor binding

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Sources of Acid Load

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Three Lines of Defense

Buffers (immediate) → Lungs (minutes) → Kidneys (hours to days)

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1. Buffer Systems (Chemical Defense)

A. Bicarbonate-CO2 System (most important ECF buffer)

• When acid (HA) is added: HA + NaHCO3 → NaA + H2O + CO2
• HCO3- is consumed but CO2 is blown off by lungs, so pH change is minimal
• pH is determined by the ratio of HCO3- to CO2 - not their absolute values

B. Other ECF Buffers

• Plasma proteins (e.g., albumin)
• Phosphate (HPO4²- / H2PO4-), pKa 6.8 - more important in urine than plasma

C. Intracellular Buffers

• Hemoglobin (major intracellular buffer in blood)
• Cellular proteins
• Organophosphate complexes
• Intracellular HCO3- and H+-HCO3- transport mechanisms

D. Bone as Buffer

• In chronic metabolic acidosis, bone acts as a major buffer reserve
• Acid-induced dissolution of bone apatite releases Ca2+ salts and HCO3- into ECF
• Chronic use leads to osteomalacia, osteoporosis, hypercalciuria, and renal stones

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2. Respiratory Regulation (Fast, Minutes)

• Acidosis stimulates the respiratory center → increased ventilation → CO2 blown off → pH rises
• Alkalosis depresses ventilation → CO2 retained → pH falls

Quantitative Respiratory Compensation:

Respiratory compensation is rapid but rarely normalizes pH completely.

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3. Renal Regulation (Slow, Hours to Days)

Net Acid Excretion (NAE):

• ~40% of NAE = Titratable acids
• ~60% of NAE = Ammonium (NH4+)
• Urinary HCO3- is essentially zero under normal conditions

Renal Mechanisms by Segment:

Proximal Tubule (reabsorbs ~80% of filtered HCO3-)

• H+ is secreted into lumen via Na+-H+ antiporter (NHE3) (2/3 of H+ secretion) and H+-ATPase (1/3)
• Secreted H+ combines with filtered HCO3- → H2CO3 → CO2 + H2O (catalyzed by carbonic anhydrase IV on brush border)
• CO2 re-enters cell → reconverted to H+ + HCO3- by carbonic anhydrase II → HCO3- exits basolateral side via NBCe1 (Na+-3HCO3- cotransporter)
• Also synthesizes NH3 (ammonia) and titrates phosphate to H2PO4-

Thick Ascending Limb (TAL)

• Reabsorbs remaining HCO3- via NHE3 (apical) and AE2/KCC4 (basolateral)

Distal Nephron / Collecting Duct

• Alpha-intercalated (α-IC) cells: secrete H+ via H+-ATPase and H+-K+-ATPase; generate new HCO3-
• Beta-intercalated (β-IC) cells: secrete HCO3- (active in alkalosis)
• The ratio of α to β cells adjusts based on chronic acid-base status

Titratable Acids

• Weak acids filtered at glomerulus that act as urinary buffers
• Most important = Phosphate (HPO4²- → H2PO4-, pKa 6.80)
• Limited capacity; under increased acid load, NH4+ excretion compensates

Ammonium (NH4+) - Major Adaptive Mechanism

• NH3 is synthesized in the proximal tubule from glutamine (glutaminase reaction)
• NH3 diffuses into tubular lumen and combines with secreted H+ → NH4+ (trapped in lumen by "ion trapping")
• NH4+ excretion can increase 10-fold in chronic acidosis - this is the primary adaptive mechanism
• NH4+ is also reabsorbed in TAL and re-secreted in collecting duct (the NH4+ recycling pathway)

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Summary Table

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Key Equations to Remember

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