Pathology : Robbins & Cotran : Adaptations of cellular growth & differentiation Hypertrophy| Hyperplasia| Atrophy | Metaplasia Hypertrophy Hypertrophy is an increase in the size of cells resulting in an increase in the size of the organ. In contrast, hyper- plasia (discussed next) is an increase in cell number. Stated another way, in pure hypertrophy there are no new cells, just bigger cells containing increased amounts of structural proteins and organelles. Hyperplasia is an adaptive response in cells capable of replication, whereas hypertro- phy occurs when cells have a limited capacity to divide. Hypertrophy and hyperplasia also can occur together, and obviously both result in an enlarged organ. Hypertrophy can be physiologic or pathologic and is caused either by increased functional demand or by growth factor or hormonal stimulation. Hyperplasia Hyperplasia is an increase in the number of cells in an organ that stems from increased proliferation, either of differentiated cells or, in some instances, less differenti- ated progenitor cells. As discussed earlier, hyperplasia takes place if the tissue contains cell populations capable of replication; it may occur concurrently with hypertrophy and often in response to the same stimuli. Hyperplasia can be physiologic or pathologic; in both situations, cellular proliferation is stimulated by growth factors that are produced by a variety of cell types.Metaplasia Metaplasia is a change in which one adult cell type (epi- thelial or mesenchymal) is replaced by another adult cell type. In this type of cellular adaptation, a cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment. Metaplasia is thought to arise by the reprogramming of stem cells.Atrophy Atrophy is shrinkage in the size of cells by the loss of cell substance. When a sufficient number of cells are involved, the entire tissue or organ is reduced in size, or atrophic 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 are pathologic (e.g., denervation), the fundamental cellular changes are similar. 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. Cellular atrophy results from a combination of decreased protein synthesis and increased protein degradation. • 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 multiple 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 also is associated with autophagy, with resulting increases in the number of autophagic vacuoles. As discussed previously, autoph- agy is the process in which the starved cell eats its own organelles in an attempt to survive.