Loop diuretics like furosemide can cause metabolic alkalosis. The mechanism is best explained by:

• A Direct inhibition of renal carbonic anhydrase, increasing bicarbonate reabsorption
• B Increased chloride reabsorption in the proximal tubule, promoting bicarbonate loss in the urine
• C Contraction alkalosis: volume depletion concentrates bicarbonate; secondary hyperaldosteronism further enhances distal Na+ reabsorption and H+/K+ secretion, generating new bicarbonate ✓
• D Potassium retention that shifts H+ extracellularly, raising serum pH

Explanation

Loop diuretics cause hypochloraemic, hypokalaemic metabolic alkalosis by two main mechanisms: (1) contraction alkalosis — volume depletion reduces GFR and promotes proportionally greater bicarbonate reabsorption in the proximal tubule (fewer litres, same bicarbonate = higher concentration); (2) secondary hyperaldosteronism from volume depletion promotes aldosterone-stimulated distal tubule Na+ reabsorption with H+ and K+ secretion, generating new bicarbonate and worsening alkalosis. Furosemide actually has mild carbonic anhydrase inhibition but this is minor. Loop diuretics do not increase chloride reabsorption; they block NKCC2 (the Na+/K+/2Cl– cotransporter).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.