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 proteasomes. This pathway is also thought to be responsible for the accelerated proteolysis seen in a variety of catabolic 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, autophagy is the process in which the starved cell eats its own organelles in an attempt to survive.
Metaplasia is a change in which one adult cell type (epithelial 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 http://ebooksmedicine.net
Fig. 2.23 Metaplasiaofnormalcolumnar(left) tosquamousepithelium(right) inabronchus,shownschematically(A)andhistologically(B).
to differentiate along a new pathway rather than a phenotypic change (transdifferentiation) of already differentiated cells.
Epithelial metaplasia is exemplified by the change that occurs in the respiratory epithelium of habitual cigarette smokers, in whom the normal ciliated columnar epithelial cells of the trachea and bronchi often are replaced by strati fied squamous epithelial cells (Fig. 2.23 ). The rugged stratified squamous epithelium may be able to survive the noxious chemicals in cigarette smoke that the more fragile specialized epithelium would not tolerate. Although the metaplastic squamous epithelium has survival advantages, important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter. Epithelial metaplasia is therefore a double-edged sword. Because vitamin A is essential for normal epithelial differentiation, its deficiency also may induce squamous metaplasia in the respiratory epithelium.
Metaplasia need not always occur in the direction of columnar to squamous epithelium; in chronic gastric reflux, the normal stratified squamous epithelium of the lower esophagus may undergo metaplastic transformation to gastric or intestinal-type columnar epithelium. Metaplasia also may occur in mesenchymal cells, but in these situations it is generally a reaction to some pathologic alteration and not an adaptive response to stress. For example, bone is occasionally formed in soft tissues, particularly in foci of injury.
The influences that induce metaplastic change in an epithelium, if persistent, may predispose to malignant transformation. In fact, squamous metaplasia of the respiratory epithelium often coexists with lung cancers composed of malignant squamous cells. It is thought that cigarette smoking initially causes squamous metaplasia, and cancers arise later in some of these altered foci.
Hypertrophy:increasedcellandorgansize,ofteninresponsetoincreasedworkload;inducedbygrowthfactorsproducedinresponsetomechanicalstressorotherstimuli;occursintissuesincapableofcelldivision
Hyperplasia:increasedcellnumbersinresponsetohormonesandothergrowthfactors;occursintissueswhosecellsareabletodivideorcontainabundanttissuestemcells
Atrophy:decreasedcellandorgansize,asaresultofdecreasednutrientsupplyordisuse;associatedwithdecreasedsynthesisofcellularbuildingblocksandincreasedbreakdownofcellularorganellesandautophagy