A patient develops intravascular hemolysis triggered by fava bean ingestion. Peripheral smear shows bite cells and Heinz bodies on crystal violet stain. The molecular basis of erythrocyte vulnerability is:

• A Pyruvate kinase deficiency causing ATP depletion
• B Hereditary spherocytosis due to spectrin deficiency
• C Deficient G6PD activity leading to NADPH depletion and inability to regenerate reduced glutathione ✓
• D HbS polymerization under oxidative stress

Explanation

G6PD is the sole source of NADPH in erythrocytes (lacking mitochondria); NADPH is required by glutathione reductase to maintain GSH. Without GSH, oxidants (from infections, drugs, or vicine/convicine in fava beans) denature hemoglobin, forming Heinz bodies. These precipitates cause membrane damage creating 'bite cells' as macrophages remove Heinz body-containing portions. PK deficiency causes hemolytic anemia but produces predominantly echinocytes and no Heinz bodies. Hereditary spherocytosis triggers extravascular, not primarily oxidative, hemolysis. HbS polymerizes under deoxygenation, not specifically oxidative stress.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.