A patient presents with hypokalaemia, metabolic alkalosis, hypertension, and low plasma renin. Aldosterone is elevated. Which physiological mechanism best explains why primary hyperaldosteronism causes hypokalaemia and metabolic alkalosis?

• A Aldosterone directly inhibits the Na-K-ATPase basolateral pump, reducing intracellular K⁺ and increasing intracellular H⁺ that diffuse into tubular lumen
• B Aldosterone stimulates the proximal tubule to secrete K⁺ via the K-Cl cotransporter, and the resulting volume expansion causes non-gap metabolic alkalosis
• C Aldosterone increases carbonic anhydrase activity in the proximal tubule, generating excess HCO3⁻ that raises plasma pH directly
• D Aldosterone activates ENaC-mediated Na⁺ reabsorption in the collecting duct, generating a lumen-negative potential that drives K⁺ secretion via ROMK and H⁺ secretion via H⁺-ATPase (intercalated cells), causing kaliuresis and bicarbonaturia-corrected metabolic alkalosis ✓

Explanation

Aldosterone binds mineralocorticoid receptors in principal cells of the cortical collecting duct: it up-regulates apical ENaC (epithelial Na⁺ channels) and basolateral Na-K-ATPase. Increased ENaC-mediated Na⁺ reabsorption creates a lumen-negative transepithelial potential difference that drives K⁺ secretion via apical ROMK channels into the tubular lumen (kaliuresis → hypokalaemia). In adjacent alpha-intercalated cells, the same electrochemical gradient and aldosterone-stimulated H⁺-ATPase drive increased H⁺ secretion into the tubular lumen (generating HCO3⁻ that returns to blood → metabolic alkalosis). Thus kaliuresis and bicarbonaturia-correction of alkalosis occur simultaneously. Aldosterone stimulates, not inhibits, basolateral Na-K-ATPase.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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