Malignant hyperthermia is a pharmacogenetic disorder resulting in a hypermetabolic state: The pathophysiology behind MH is related to an uncontrolled release of intracellular calcium ions (Ca2+) from skeletal muscle sarcoplasmic reticulum. This uncontrolled release of calcium causes a rise in myoplasmic calcium which results in myofibrillary contractions and sustained muscle contractions. These contractions eventually result in rapid depletion of Adenosine Triphosphate (ATP) which further results in muscle cell damage and rhabdomyolysis. The depletion in the stores of the energy molecules, ATP, also results in excessive oxygen consumption, increase in glucose metabolism, carbon dioxide production and excessive heat production. The most common cause of impaired calcium regulation in MH is due to the presence of defective RYR1 gene (ryanodine receptors) in the sarcoplasmic reticulum. Other major proteins responsible for the calcium dysregulation include DHPR (dihydropyridine receptors), FK506, and triadin. | Abbreviations: Ca2+, calcium; DHP receptor, dihydropyridine receptor; MH, malignant hyperthermia; RYR1, ryanodine receptor subtype 1 | Schneiderbanger, D., Johannsen, S., Roewer, N., & Schuster, F. (2014). Management of malignant hyperthermia: diagnosis and treatment. Therapeutics and clinical risk management, 10, 355–362.

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