A 25-year-old man of West African origin develops acute intravascular hemolysis after starting primaquine. The underlying enzyme deficiency causes hemolysis by which mechanism?

• A Impaired globin chain synthesis reduces hemoglobin solubility
• B Defective spectrin crosslinking causes membrane fragmentation during splenic transit
• C Reduced NADPH impairs glutathione regeneration, leaving RBCs vulnerable to oxidative damage ✓
• D Complement activation on RBC surface triggers MAC-mediated lysis

Explanation

G6PD deficiency impairs the hexose monophosphate shunt, reducing NADPH generation. NADPH is required to maintain glutathione in its reduced form; without adequate reduced glutathione, oxidative stress from primaquine or dapsone causes hemoglobin oxidation to Heinz bodies and RBC membrane damage leading to hemolysis. Spectrin defects characterize hereditary spherocytosis; complement-mediated lysis characterizes PNH.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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