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Fatigue is a sensation caused by a buildup of lactic acid in the muscles, characterized by aching and pain, plus loss of voluntary muscle control. It is typical when engaging in difficult exercise and is caused by the anaerobic (i.e. without oxygen) conversion of glucose to energy which occurs when the bloodstream cannot deliver oxygen to cells.
Fatigue is normal after exercise, such as climbing several sets of stairs, walking for several miles, or running. It will pass when the muscles are allowed to rest and no longer have demand for oxygen. At that point, the lactic acid is recombined with oxygen to form carbon dioxide and water.
However, fatigue after a short period of exercise (for example, climbing one flight of stairs) is not normal and is usually the sign of an underlying illness. It is usually a problem with the lungs (such as emphysema or pulmonary fibrosis) or the heart (typically congestive heart failure or arythmia).
Constant fatigue is not unheard of, where a person feels fatigue even after short exertions, such as walking across a room. Such conditions are poorly understood, but have well established diagnostic criteria. They usually have no clear course of treatment. The two best described are chronic fatigue syndrome (which can often be a complication of infections) and fibromyalgia (which follows traumatic injury).
Fatigue in a person at rest is usually the sign of a serious underlying illness and requires immediate medical treatment.