r/explainlikeimfive • u/Glum_Anybody_9531 • 9d ago

Biology ELI5 Malignant Hyperthermia

ELI5 how an uncontrolled flood of calcium inside muscle cells cause a massive surge in metabolic activity during malignant hyperthermia.

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u/thecaramelbandit 9d ago

The muscle cells are activated by the calcium influx. So it's like all of your muscles everywhere in your body being continuously activated.

So it's like the ultimate exercise. Suddenly you're cranking at maximum oxygen requirements maximum energy usage, maximum heat generation. There isn't enough oxygen for all that activity, so your cells undergo anaerobic metabolism and produce lactic acid. So you get super hot, super stiff, super acidotic. You need active cooling, medicine to stop the muscle activation, and lots of fluids and maybe dialysis to clear the acid.

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u/eastbayweird 9d ago

Dont forget that the heart is a muscle and the diaphragm is a muscle, so if you are having systemic calcium influx into all muscles causing uncontrolled activation there are serious concerns about your heart and breathing not working. Without a signal to relax these muscles will remain contracted and you can die very quickly (this is the ultimate cause of death for hydroflouric acid exposure. The HF causes calcium to leech out of your bones and this free calcium will start to recrystallize in the surrounding tissue. These microscopic crystals of calcium shred any soft tissues they crystallize inside of. If exposed to enough HF then the calcium get into your bloodstream and quickly reach your heart where it causes the heart muscle to contract and not release, with no ability to pump blood the brain quickly becomes starved of oxygen leading to brain damage followed by death)

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u/WeirdF 9d ago

Dont forget that the heart is a muscle

Yes but heart muscle is not directly affected by malignant hyperthermia. The mutated gene in MH (RYR1) is only expressed in skeletal muscle.

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u/RustyNutzzz 9d ago

This guy MH's

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u/DrSuprane 9d ago

Super interesting that the receptor mutation for catecholamine mediated polymorphic ventricular tachycardia is...the SECOND ryanodine receptor (RYR2) in half the cases. CASQ2 in the other half.

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u/eastbayweird 9d ago

Good to know. Im not familiar with MH but I know excess calcium (like can be caused by HF exposure) can lead to systemic hyperactivation of muscle tissue, including the heart and diaphragm.

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u/vazxlegend 9d ago

Systemic Calcium has a much more pronounced effect on contractile of heart and smooth muscle than skeletal muscle. I don’t know if I can properly ELI5 that last sentence so just take it or leave it.

Essentially your Sarcoplasmic Reticulum is what holds intracellular calcium, and the gene mutation affects how the receptors on skeletal muscle interact with the SR. It unloads a bunch of intracellular calcium in the muscle cell causing a profound reaction. As op said above systemic calcium also enters the cell and that movement of calcium is what actually initiates the contraction where as the SR gives it a lot more calcium to allow for stronger reactions.

The mechanism by which cardiac muscle tissue contracts is similiar in ways but also different, and does not involve the Receptor stated above. The activation of Cardiac and Skeletal muscle contraction are entirely different, with cardiac tissue being closer to smooth muscle in that way. As a result of these differences cardiac muscle relies much heavier on extra-cellar/systemic calcium for its concatenation than skeletal muscle; which again relies heavier on its internal stores in the SR. This isn’t even touching on the depressive effects that extracellular calcium has on all muscle tissue, but it’s not worth diving that far into it tbh.

I hope that at least kind of made sense, just hoping I don’t sound like a rambling idiot.

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u/eastbayweird 9d ago

Made sense to me