If the fatigue is general, or "all over," it is from these waste substances piling up in the blood faster than the lungs, skin, and kidneys can get rid of them.
In other words, fatigue is a form of self-poisoning.
We can see how it is that exercise, which, up to the point of fatigue, is both healthful and improving, when carried on after we are tired, becomes just the opposite.

Fatigue is nature's signal, "Enough for this time!" That is why all methods of training for building up strength and skill, both of mind and muscle, forbid exercising beyond well-marked fatigue.

If you yourself stop at this point in exercising, you will find, the next time you try that particular exercise, that you can go a little further before fatigue is felt; the third time, a little further yet; and so, by degrees, you can build up both your body and brain to the fullest development of which they are capable.
In muscular training, a series of light, quick movements, none of which are fatiguing, repeated fifteen, twenty, or a hundred times, will do much more to build up muscle and increase strength, than three or four violent, heaving strains that tax all your strength.

Real athletes and skilled trainers, for instance, use half-or three-quarter-pound dumb-bells and one-or two-pound Indian clubs, instead of the five-pound dumb-bells and ten-pound clubs with which would-be athletes delight to decorate their rooms.

A thoroughbred race-horse is trained on the same principle: he is never allowed to gallop until tired, or to put out his full speed before he is well grown.