Type 4 renal tubular acidosis (RTA) is most commonly caused by hypoaldosteronism. The mechanism by which aldosterone deficiency causes hyperkalemic metabolic acidosis is:

• A Aldosterone deficiency reduces Na-K-ATPase in the proximal tubule, impairing HCO3- reabsorption
• B Aldosterone normally stimulates principal cell sodium reabsorption, generating lumen-negative voltage that drives passive K+ and H+ secretion in alpha-intercalated cells; deficiency reduces this electrochemical driving force for both K+ and H+ secretion ✓
• C Hyperkalemia directly activates ammoniagenesis inhibitors, reducing NH3 availability for urinary acidification
• D Aldosterone deficiency impairs H-K-ATPase in the collecting duct, the primary proton pump for urinary acidification

Explanation

Aldosterone acts on collecting duct principal cells via mineralocorticoid receptors, stimulating apical ENaC (epithelial sodium channel) expression and basolateral Na-K-ATPase. Sodium entry through ENaC into principal cells creates a lumen-negative transepithelial voltage (approximately -40 mV), which provides the electrochemical driving force for both K+ secretion (via ROMK/BK channels in principal cells) and H+ secretion (via H-ATPase in adjacent type A/alpha-intercalated cells). With aldosterone deficiency (e.g., Addison's disease, hyporeninemic hypoaldosteronism in diabetic nephropathy), reduced lumen-negative potential impairs both K+ and H+ secretion, causing hyperkalemia and hyperchloremic (non-anion-gap) metabolic acidosis. Option C (hyperkalemia inhibiting ammoniagenesis) is a secondary contributory mechanism in type 4 RTA.

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

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