A patient on loop diuretics develops severe hypokalemia. The mechanism by which furosemide causes hypokalemia involves which tubular segment and which electrophysiological consequence in the heart?

• A Furosemide blocks the cortical collecting duct principal cell Na-K-ATPase directly; cardiac consequence is peaked T waves
• B Furosemide directly inhibits the H-K-ATPase in the collecting duct intercalated cells, reducing K+ absorption
• C Furosemide inhibits NKCC2 in thick ascending limb → increased Na+ delivery to collecting duct → Na+ reabsorption via ENaC → lumen-negative electrochemical gradient drives K+ secretion via ROMK channels; cardiac: hypokalemia reduces resting membrane potential, causing QT prolongation and torsades de pointes risk ✓
• D Secondary hyperaldosteronism from volume depletion increases K+ reabsorption (not secretion) in the collecting duct

Explanation

Furosemide inhibits NKCC2 (Na-K-2Cl cotransporter) in the thick ascending limb of Henle, delivering more Na+ to the cortical collecting duct (CCD). In the CCD, principal cells reabsorb Na+ via ENaC (epithelial sodium channel), creating a lumen-negative electrical gradient that drives K+ secretion through ROMK channels (and Cl- via ClC-K). Volume depletion also activates RAAS, causing aldosterone-driven ENaC upregulation and further K+ secretion. Hypokalemia reduces the resting membrane potential of cardiac cells, prolonging action potential duration (phase 3 repolarization via Ik) — manifesting as QT prolongation and predisposing to polymorphic VT (torsades de pointes).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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