When confronted with a decrease in work demands or adverse environmental conditions, most cells are able to revert to a smaller size and a lower and more efficient level of functioning that is compatible with survival. This decrease in cell size is called atrophy and is illustrated in Figure 5.1 regarding atrophy of the endometrium. Cells that are atrophied reduce their oxygen consumption and other cellular functions by decreasing the number and size of their organelles and other structures. There are fewer mitochondria, myofilaments, and endoplasmic reticulum structures. When a sufficient number of cells are involved, the entire tissue or muscle atrophies.
Cell size, particularly in muscle tissue, is related to work-load. As the workload of a cell declines, oxygen consumption and protein synthesis decrease. Furthermore, proper muscle mass is maintained by sufficient levels of insulin and insulin-like growth factor-1 (IGF-1). When insulin and IGF-1 levels are low or catabolic signals are present, muscle atrophy occurs by mechanisms that include reduced synthetic processes, increased proteolysis by the ubiquitin–proteasome system, and apoptosis or programmed cell death. In the ubiquitin–protea-some system, intracellular proteins destined for destruction are covalently bonded to a small protein called ubiquitin and then degraded by small cytoplasmic organelles called proteasomes. The general causes of atrophy can be grouped into five categories:
• Loss of endocrine stimulation
• Inadequate nutrition
• Ischemia or decreased blood flow
Disuse atrophy occurs when there is a reduction in skeletal muscle use. An extreme example of disuse atrophy is seen in the muscles of extremities that have been encased in plaster casts. Because atrophy is adaptive and reversible, muscle size is restored after the cast is removed and muscle use is resumed. Denervation atrophy is a form of disuse atrophy that occurs in the muscles of paralyzed limbs. Lack of endocrine stimulation produces a form of disuse atrophy. In women, the loss of estrogen stimulation during menopause results in atrophic changes in the reproductive organs. With malnutrition and decreased blood flow, cells decrease their size and energy requirements as a means of survival.