In ischemia-reperfusion injury, the paradoxical worsening upon restoration of blood flow is primarily attributable to which mechanism?
- A Massive generation of reactive oxygen species from xanthine oxidase and mitochondria ✓
- B Sudden restoration of ATP causing uncontrolled calcium influx
- C Rapid decrease in intracellular pH causing protein denaturation
- D Osmotic lysis due to rapid cellular rehydration
Correct answer: A. Massive generation of reactive oxygen species from xanthine oxidase and mitochondria
Explanation
In reperfusion injury, reintroduction of oxygen to ischemic tissue causes a burst of ROS generated from: (1) xanthine oxidase — hypoxanthine accumulated during ischemia is rapidly oxidized upon oxygen delivery; (2) dysfunctional mitochondrial electron transport chain; and (3) activated neutrophils. These ROS cause lipid peroxidation, protein oxidation, and mitochondrial permeability transition. Calcium overload also contributes but ROS burst is the primary early driver.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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