In exertional heat stroke, thermoregulatory failure leads to hyperthermia >41°C. Which cellular mechanism primarily underlies the multi-organ dysfunction in this condition?
- A Direct thermal protein denaturation and mitochondrial uncoupling causing cellular energy failure ✓
- B Lactic acidosis from anaerobic metabolism overwhelming buffer systems
- C Hypotension from vasodilation reducing organ perfusion
- D Intravascular hemolysis causing free hemoglobin-mediated organ toxicity
Correct answer: A. Direct thermal protein denaturation and mitochondrial uncoupling causing cellular energy failure
Explanation
Above 41-42°C, thermal denaturation of structural and enzymatic proteins occurs, with disruption of mitochondrial function — including uncoupling of oxidative phosphorylation. This cellular energy failure, combined with increased reactive oxygen species, triggers coagulopathy (DIC), rhabdomyolysis, renal tubular necrosis, hepatocellular injury, and cerebral edema. Hypotension (option C) contributes but is a consequence rather than the primary cellular mechanism. Lactic acidosis (option B) and hemolysis (option D) may occur but are secondary features.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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