Malignant hyperthermia

Question 1

Genetics

Answer 1

Dominant.
RYR1 mutations in 70%

Environmental disorder! exposure to anesthesia (specifically halothane or succinylcholine)!! know.

Question 2

Phenotype

Answer 2

Hypermetabolism, skeletal muscle damage, hyperthermia

Death if untreated, 70% mortality untreated

Question 3

Mechanism

Answer 3

Ca transport from the SR into the sarcoplasm is an integral component of the normal E-C process and is mediated by the RYR. Which is affected by conformational change in DHPR.
Inherited susceptibility to MH is conferred by an abnormal skeletal muscle RYR1 or associated structure that allows abnormal Ca release when exposed to an anesthetic triggering agent. mechanism is unknown, but prolonged RYR1 channel opening has been demonstrated in an experimental model.
Dantrolene sodium, the treatment for MH, helps RYR close.

In MH, accumulation of abnormally high levels of Ca in the sarcoplasm causes uncontrolled anaerobic and aerobic metabolism and sustained muscle cell contraction. (ATP) depletion eventually causes widespread muscle fiber hypoxia

Question 4

Signs?

Answer 4

Muscle rigidity (Masseter spasm)
Increased CO2 production
Rhabodomyolysis
Hyperthermia

Can do caffeine/halothane test on muscle biopsy.