Malignant hyperthermia (MH) crisis is triggered by succinylcholine and volatile anaesthetics. The primary biochemical defect involves which molecular target?

• A Defective sarcolemmal calcium channels (L-type) releasing excess extracellular calcium
• B Uncoupling of ATP synthesis from mitochondrial proton gradient
• C Autoimmune destruction of fast sodium channels in skeletal muscle
• D Mutation in ryanodine receptor (RYR1) causing uncontrolled Ca2+ release from sarcoplasmic reticulum ✓

Explanation

Malignant hyperthermia is a pharmacogenetic disorder caused predominantly by mutations in the skeletal muscle ryanodine receptor (RYR1 gene, chromosome 19q13.2). Triggering agents (volatile anaesthetics, succinylcholine) cause uncontrolled RYR1 channel opening, massive calcium efflux from the sarcoplasmic reticulum, sustained myofilament activation, and explosive hypermetabolism. Clinical features include hyperthermia, rigidity, rhabdomyolysis, acidosis, and hypercarbia. Dantrolene (2.5 mg/kg, repeat to 10 mg/kg) blocks RYR1 and is the specific antidote.

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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