fatigue, in physiology, inability to perform reasonable and necessary physical or mental activity. Muscle fatigue, for example, results when the contractile properties of muscle are reduced, and continued exertion is impossible unless the muscle is allowed to rest. In muscle tissue, the depletion of glycogen (stored glucose), a source of energy for muscle cells, and the accumulation of lactic acid, which is produced through the breakdown of glucose, was long thought to the cause of muscle fatigue, but it is now known that the lactic acid produced is used as an energy source as well. A new explanation of muscle fatigue suggests that it is related to the control of the flow of the calcium ions in muscle. The release of those ions causes muscle contraction, while their storage causes relaxation. After prolonged exercise, the channels that control calcium flow become leaky, diminishing the muscle cells ability to contract. In the normal body the damaged channels are repaired after a period of rest. There are some persons in whom fatigue is a chronic state that does not necessarily result from activity or exertion. In some instances this abnormal fatigue may be associated with systemic disorders such as anemia, a deficiency of protein or oxygen in the blood, addiction to drugs, increased or decreased function of the endocrine glands, or kidney disease in which there is a large accumulation of waste products. If excessive fatigue occurs over a prolonged period, exhaustion (marked loss of vital and nervous power) may result. In most persons with chronic fatigue, however, the condition seems to be associated with bipolar disorder. Thorough medical and psychiatric examination may be required.