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Acid buildup in muscle tissue. Here is an article that explains what is happening:
Esit: I originally said that your.muscles are creating waste chemicals quicker than your bloodstream can handle causing those bad chemicals build up locally. While this is true in a broader sense, I think it is more nuanced that that. Reading the article should give a better explaination
2001: A Space Odyssey still holds up pretty well both technically and narratively.