A patient with primary adrenal insufficiency (Addison's disease) develops hyponatremia, hyperkalemia, and hypotension. Aldosterone deficiency causes hyperkalemia primarily by which mechanism?

• A Reduced Na+/K+-ATPase activity in proximal tubule cells reduces cellular K+ accumulation and luminal secretion
• B Impaired H+/K+-ATPase in type A intercalated cells directly retains K+ while secreting H+
• C Decreased GFR from hypotension reduces filtered K+ load, impairing K+ excretion
• D Reduced ENaC activity in principal cells decreases lumen-negative potential, impairing K+ secretion through ROMK channels in the collecting duct ✓

Explanation

Aldosterone binds to mineralocorticoid receptors in principal cells of the cortical collecting duct, upregulating ENaC (apical Na+ channel) and the basolateral Na+/K+-ATPase. ENaC-mediated Na+ reabsorption creates a lumen-negative electrochemical gradient that drives K+ secretion through apical ROMK (Kir1.1) channels into the tubular lumen. Without aldosterone, ENaC activity falls, the lumen-negative potential is lost, ROMK-mediated K+ secretion is impaired, and plasma K+ rises (hyperkalemia). Simultaneously, reduced ENaC means less Na+ reabsorption and more NaCl in the urine, causing hyponatremia and volume depletion.

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

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