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Aldosterone Site of Action — FRCA Primary MCQ

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HardPhysiology - RenalAldosterone Site of ActionFRCA Primary

A patient starts spironolactone while taking an ACE inhibitor. Which distal-nephron change best accounts for the increased risk of hyperkalaemia?

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Correct answer: B — Reduced aldosterone-mediated ENaC activity decreases the driving force for potassium secretion

The best answer is “Reduced aldosterone-mediated ENaC activity decreases the driving force for potassium secretion”. Spironolactone antagonises mineralocorticoid receptors in principal cells, reducing ENaC activity and the lumen-negative potential that promotes potassium secretion through ROMK. Combined renin–angiotensin blockade further reduces aldosterone signalling. NKCC2 and SGLT2 are upstream transporters, and AQP2 controls water permeability rather than the main potassium-secretion driving force.

Reference: RCoA, Primary FRCA syllabus: https://www.rcoa.ac.uk/sites/default/files/documents/2026-01/Primary-FRCA-Syllabus.pdf; Collecting-duct principal-cell transport processes: https://pmc.ncbi.nlm.nih.gov/articles/PMC4284417/