Shrinkage in the size of the cell by loss of cell substance is known as atrophy. It represents a form of adaptive response. 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 notocord or 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 basic cause and can be local or generalized. The common causes of atrophy are the following:

Decreased workload (atrophy of disuse): When a broken limb is immobilized in aplaster cast or when a patient is testricted to complete bed rest, skeletal muscle atrophy rapidly ensues. The initial rapid decrease in cell size is reversible when activity is resumed. With more prolonged disuse, skeletal muscle fibers decrease in number as well as in size and 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 occulsive disease results in atrophy of tissue owing to progressive cell loss. In late elder life, the brain undergoes progressive atrophy presumably as atherosclerosis narrows its blood supply.

Inadequate utrition: profound protein calorie malnutrition 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.

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

Agine (senile atrophy): The aging process is associated with cell loss. Morphologically, it is seen in tissues containing permanent cells, particularly in 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 a blood supply that has been compromised by the expanding mass.

The fundamental cellular changes are identical in all of these settings representing a retreat by the cell to a smaller size at which survival is still possible. Atrophy represents a reduction in structural components of the cell. In muscle the cells contain fewer mitocondria and myofilaments and a lesser amount of endoplasmic reticulum. By bringing into balance cell volume and lower levels of blood supply nutrition or triphic stimulation a new equlibrium is achieved. Although atrophic cells may have diminished function, they are not dead. Apoptosis or programmed cell death, however 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 and the shrinkage of secretory glands after obstruction of their ducts.

The biochemical mechanisms responsible for atrophy are incompletely understood but are likely to affect the balance between protein synthesis and degradation. The regulation of protein degradation probably plays a key role in atrophy. Mammalian cells contain multiple proteolytic systems that serve distinct function Lysosomes contain acid hyrolases 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 degraded by this process are first conjugated to ubiquitin and then degraded within a large cytoplasmic proteolytic complex or proteasome. This pathway is thought to be responsible for the accelerated proteolysis 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 TNF-? and IL-1? are capable of signaling accelerated muscle proteolysis by way of this mechanism.