Definition: Decrease in the size of cells, tissues, or organs. Causes of atrophy include poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise, or disease intrinsic to the tissue itself. Hormonal and nerve inputs that maintain an organ or body part are referred to as trophic.

Atrophy is a general physiological process of reabsorption and breakdown of tissues, involving apoptosis on a cellular level. It can be part of normal body development and homeostatic processes, or as a result of disease. Atrophy resulting from disease of the tissue itself, or loss of trophic support due to other disease is termed pathological atrophy.

Shrinkage in the size of the cell by loss of cell substance is known as atrophy. It represents a form of adaptive response and may culminate in cell death.

When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, or becomes atrophic. Atrophy can be physiologic or pathologic.

 Physiologic atrophy is common during early development. Some embryonic structures, such as the notochord and thyroglossal duct, undergo atrophy during fetal development. The uterus decreases in size shortly after parturition, and this is a form of physiologic atrophy.

 Pathologic atrophy depends on the underlying cause and can be local or generalized. The common causes of pathologic atrophy are the following:

• Decreased workload (atrophy of disuse)
  • When a broken limb is immobilized in a plaster cast or when a patient is restricted to complete bed rest, skeletal muscle atrophy rapidly ensues. The initial rapid decrease in cell size is reversible once activity is resumed. With more prolonged disuse, skeletal muscle fibers decrease in number as well as in size; this atrophy can be accompanied by increased bone resorption, leading to osteoporosis of disuse. Loss of innervation (denervation atrophy). Normal function of skeletal muscle is dependent on its nerve supply. Damage to the nerves leads to rapid atrophy of the muscle fibers supplied by those nerves.

• Diminished blood supply.
  • A decrease in blood supply (Ischemia) to a tissue as a result of arterial occlusive disease results in atrophy of tissue owing to progressive cell loss. In late adult life, the brain undergoes progressive atrophy, presumably as atherosclerosis narrows its blood supply.

• Inadequate nutrition.
  • Profound protein-calorie malnutrition (marasmus) is associated with the use of skeletal muscle as a source of energy after other reserves such as adipose stores have been depleted. This results in marked muscle wasting (cachexia). Cachexia is also seen in patients with chronic inflammatory diseases and cancer. In the former, chronic overproduction of the inflammatory cytokine tumor necrosis factor (TNF) is thought to be responsible for appetite suppression and muscle atrophy.

• Loss of endocrine stimulation
  • Many endocrine glands, the breast, and the reproductive organs are dependent on endocrine stimulation for normal metabolism and function. The loss of estrogen stimulation after menopause results in physiologic atrophy of the endometrium, vaginal epithelium, and breast.

• Aging (senile atrophy)
  • The aging process is associated with cell loss, typically seen in tissues containing permanent cells, particularly the brain and heart.

• Pressure
  • Tissue compression for any length of time can cause atrophy. An enlarging benign tumor can cause atrophy in the surrounding compressed tissues. Atrophy in this setting is probably the result of ischemic changes caused by compromise of the blood supply to those tissues by the expanding mass.

Pathogenesis

 The fundamental cellular changes associated with atrophy are identical in all of these settings, representing a retreat by the cells to a smaller size at which survival is still possible. Atrophy results from a reduction in the structural components of the cell.

 In atrophic muscle, the cells contain fewer mitochondria and myofilaments and a reduced amount of endoplasmic reticulum. By bringing into balance cell volume and lower levels of blood supply, nutrition, or trophic stimulation, a new equilibrium is achieved.

 Although atrophic cells may have diminished function, they are not dead. However, atrophy may progress to the point at which cells are injured and die. In ischemic tissues, if the blood supply is inadequate even to maintain the life of shrunken cells, injury and cell death may supervene. Furthermore, apoptosis may be induced by the same signals that cause atrophy and thus may contribute to loss of organ mass. For example, apoptosis contributes to the regression of endocrine organs after hormone withdrawal.

 The biochemical mechanisms responsible for atrophy are incompletely understood but are likely to affect the balance between protein synthesis and degradation.

 Increased protein degradation

• Increased protein degradation probably plays a key role in atrophy. Mammalian cells contain multiple proteolytic systems that serve distinct functions.
• Lysosomes contain acid hydrolases (e.g., cathepsins) and other enzymes that degrade endocytosed proteins from the extracellular environment and the cell surface as well as some cellular components.
• The ubiquitin-proteasome pathway is responsible for the degradation of many cytosolic and nuclear proteins. Proteins to be degraded by this process are first conjugated to ubiquitin and then degraded within a large cytoplasmic proteolytic organelle called the proteasome. This pathway is thought to be responsible for the accelerated proteolysis seen in a variety of catabolic conditions, including cancer cachexia.

 Hormones, particularly glucocorticoids and thyroid hormone, stimulate proteasome-mediated protein degradation; insulin opposes these actions. Additionally, cytokines, such as tumor necrosis factor (TNF), are capable of increasing muscle proteolysis by way of this mechanism.

 In many situations, atrophy is also accompanied by marked increases in the number of autophagic vacuoles (autophagy).

See also

 hypoplasia
 hypotrophy

References

 Robbins