Compound A (methoxyflurane degradation product) is nephrotoxic because it liberates inorganic fluoride. The critical renal injury from inorganic fluoride is primarily due to which mechanism?

• A Glomerular basement membrane disruption by fluoride ions
• B Direct toxicity to juxtaglomerular apparatus reducing renin secretion
• C Precipitation of calcium fluoride crystals in tubular lumina
• D Inhibition of renal tubular Na-K-ATPase leading to concentrating defect ✓

Explanation

High inorganic fluoride levels (above ~50 µmol/L) impair renal tubular Na-K-ATPase, blunting the medullary concentration gradient and producing a vasopressin-resistant nephrogenic diabetes insipidus (high-output renal failure). Sevoflurane also generates inorganic fluoride but to a lesser extent; however, sevoflurane is degraded intrarenal at the site of action, making it nephrotoxic mainly in the context of prolonged low-flow (Compound A risk) rather than systemic fluoride peaks.

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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