* Shrinkage in the size of the cell by the loss of cell substance is known as atrophy * Although atrophied cells have diminished its function, they are not dead Shrinkage in the size of the cell by the loss of cell substance is known as atrophy. When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, becoming atrophic (Fig. 1-4). Although atrophic cells may have diminished function, they are not dead. Causes of atrophy include a decreased workload (e.g., immobilization of a limb to permit healing of a fracture), loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, and aging (senile atrophy). Although some of these stimuli are physiologic (e.g., the loss of hormone stimulation in menopause) and others pathologic (e.g., denervation), the fundamental cel- lular changes are identical. They represent a retreat by the cell to a smaller size at which survival is still possible; a new equilibrium is achieved between cell size and dimin- ished blood supply, nutrition, or trophic stimulation. The mechanisms of atrophy consist of a combination of decreased protein synthesis and increased protein degradation in cells. * Protein synthesis decreases because of reduced meta- bolic activity. * The degradation of cellular proteins occurs mainly by the ubiquitin-proteasome pathway. Nutrient deficiency and disuse may activate ubiquitin ligases, which attach mul- tiple copies of the small peptide ubiquitin to cellular proteins and target them for degradation in protea- somes. This pathway is also thought to be responsible for the accelerated proteolysis seen in a variety of cata- bolic conditions, including the cachexia associated with cancer. * In many situations, atrophy is also accompanied by increased autophagy, with resulting increases in the number of autophagic vacuoles. Autophagy ("self-eating") is the process in which the starved cell eats its own components in an attempt to survive. We describe this process later in the chapter. Refer robbins 9/e p4-5