Describe the role of the kidney in the regulation of acid–base balance. Explain bicarbonate reabsorption, titratable acid and the ammonia mechanism.

Introduction

• Three lines of defence, in order of speed:

– Buffers — act in seconds

– Respiratory — acts in minutes; removes volatile acid (CO2)

– Renal — acts over hours to days; the only route for non-volatile acid, and the only one that truly corrects

Buffer Systems

• The ratio HCO3− : H2CO3 = 20 : 1 is what determines pH, not the absolute values

Renal Mechanisms — Overview

1. Reabsorption of filtered bicarbonate — prevents loss of base

2. Excretion of H+ as titratable acid

3. Excretion of H+ as ammonium

4. Generation of new bicarbonate

Bicarbonate Reabsorption (chiefly PCT — 85%)

H+ secreted into lumen (Na+–H+ exchanger) → H+ + filtered HCO3− → H2CO3 → Luminal carbonic anhydrase → CO2 + H2O → CO2 diffuses into the cell → Intracellular CA reforms H2CO3 → H+ + HCO3− → HCO3− returns to blood; H+ resecreted

• Note that the bicarbonate returning to blood is not the same molecule that was filtered
• No net H+ excretion occurs — this step only conserves base
• Acetazolamide blocks carbonic anhydrase → bicarbonate loss → metabolic acidosis

Titratable Acid (phosphate Buffer)

Secreted H+ + HPO42− → H2PO4− excreted in urine → For each H+ excreted, one new HCO3− is added to blood

• Accounts for 10–30 mEq H+/day
• Limited by the amount of filtered phosphate available
• Titratable acid = the amount of NaOH needed to titrate urine back to pH 7.4

Ammonia Mechanism — the Adaptable One

Glutamine taken up by PCT cell → Glutaminase → NH4+ + glutamate → Glutamate → α-ketoglutarate → 2 HCO3− → NH4+ secreted into lumen → Excreted as NH4Cl

• Accounts for 30–50 mEq/day normally
• Can increase up to 10-fold in chronic acidosis — the most important adaptive mechanism
• Takes 3–5 days to reach full capacity
• NH3 is lipid-soluble and diffuses in; NH4+ is charged and is trapped in the acid urine — "diffusion trapping"

Factors Affecting H⁺ Secretion

• Note the reciprocal relation between K+ and H+: hypokalaemia drives H+ into cells → intracellular acidosis in the tubule → ↑ H+ secretion → paradoxical aciduria in metabolic alkalosis from vomiting

Acid–base Disorders

Applied Aspects

• Anion gap = Na+ − (Cl− + HCO3−); normal 8–16 mEq/L. ↑ in ketoacidosis, lactic acidosis, uraemia, poisoning
• Renal tubular acidosis — type 1 (distal, cannot secrete H+), type 2 (proximal, cannot reabsorb HCO3−); both give normal anion gap acidosis
• Chronic renal failure → failure of ammonia production and acid excretion → metabolic acidosis with high anion gap
• Compensation is never complete — pH is returned toward, but not to, normal
• Winter formula — expected PCO2 = (1.5 × HCO3−) + 8 ± 2; a deviation indicates a second, mixed disorder
• Vomiting → loss of HCl → metabolic alkalosis with hypokalaemia and paradoxical aciduria