Etiology and pathophysiology of malignant hyperthermia.
MH occurs in people who have a generalized membrane abnormality. Two clinical myopathies are known to be associated with this membrane defect. One is usually subclinical and is inherited as a mendelian dominant characteristic. The other occurs in boys who have a number of striking physical abnormalities, and is inherited as a recessive trait. When the abnormal muscle cell membrane is exposed to anesthetic agents such as halothane or succinylcholine there is a rapid, excessive release of calcium into the myoplasm. The raised myoplasmic calcium concentration leads to all the clinical features of the syndrome, predominant among which are: metabolic acidosis, a rise in body temperature, and rigidity--particularly in the muscles of the limbs. The exact site and nature of the lesion in the muscle cell membrane are still to be determined, but recent evidence suggests that it may lie in the E-C coupling mechanism. Understanding of the pathophysiology of MH has led to the development of an appropriate drug treatment for this syndrome, the aim of which is to restore the elevated myoplasmic calcium level to normal. Dantrolene sodium promises to be the most effective drug in achieving this result.
D000769:Anesthesia, Inhalation / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D003620:Dantrolene / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000648:ultrastructure; D008297:Male; D008305:Malignant Hyperthermia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009119:Muscle Contraction; D009132:Muscles / Q000648:ultrastructure; D009135:Muscular Diseases / Q000150:complications; D009210:Myofibrils / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000150:complications; D012508:Sarcolemma / Q000378:metabolism; D013552:Swine
D003620:Dantrolene; D002118:Calcium