Loop diuretics cause hypokalaemia and metabolic alkalosis. Which mechanism best explains the alkalosis?
- A Frusemide directly inhibits carbonic anhydrase in the collecting duct, reducing H+ secretion
- B Volume contraction raises aldosterone; aldosterone stimulates H+-K+-ATPase in the collecting duct to secrete H+ in exchange for K+ reabsorption, and urinary H+ loss generates new HCO3- ✓
- C K+ depletion itself causes alkalosis by shifting H+ intracellularly in exchange for K+ exiting cells, raising extracellular pH
- D Frusemide enhances chloride reabsorption in the collecting duct, leaving excess HCO3- in plasma
Correct answer: B. Volume contraction raises aldosterone; aldosterone stimulates H+-K+-ATPase in the collecting duct to secrete H+ in exchange for K+ reabsorption, and urinary H+ loss generates new HCO3-
Explanation
Loop diuretics cause volume depletion, activating the renin-angiotensin-aldosterone system. Aldosterone acts on alpha-intercalated cells of the cortical collecting duct, stimulating H+-ATPase (vacuolar) and H+/K+-ATPase to secrete H+ into the tubular lumen; for each H+ secreted, one new HCO3- is generated and reabsorbed into plasma. Additionally, hypokalaemia shifts H+ intracellularly (contributing to alkalosis, option C), but the aldosterone-driven distal H+ secretion is the primary mechanism of loop-diuretic-induced metabolic alkalosis.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.