Malignant hyperthermia is triggered by inhalational anesthetics and succinylcholine in susceptible individuals. The primary mechanism causing hyperthermia is:

• A Dysregulation of hypothalamic set-point by muscular prostaglandin release
• B Mitochondrial uncoupling of oxidative phosphorylation in skeletal muscle
• C Excessive acetylcholine accumulation at neuromuscular junctions causing tetanic contraction
• D Uncontrolled Ca2+ release from sarcoplasmic reticulum via mutant RyR1 receptors causing sustained muscle contraction and thermogenesis ✓

Explanation

Malignant hyperthermia results from mutations in the ryanodine receptor 1 (RyR1) gene — triggering agents cause uncontrolled Ca2+ release from the sarcoplasmic reticulum, leading to sustained muscle contraction, massive ATP hydrolysis, and heat production. Unlike fever, the hypothalamic set-point is NORMAL — it is a peripheral hyperthermia not mediated by pyrogens. Treatment is dantrolene, which blocks RyR1-mediated Ca2+ release. Core temperatures can exceed 40–41°C rapidly.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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