Hypertrophy

Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ. In contrast, hyperplasia is characterized by an increase in cell number because of proliferation of differentiated cells and replacement by tissue stem cells. 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 cellscapable of replication, whereas hypertrophy occurs when cells have a limited capacity to divide. Hypertrophy and hyperplasia also can occur together, and obviously both result in an enlarged (hypertrophic) organ.

Hypertrophy can be physiologic or pathologic and is caused either by increased functional demand or by growth factor or hormonal stimulation.

• The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogenstimulated smooth muscle hypertrophy and smooth muscle hyperplasia (Fig. 1–3). In contrast, in response to increased demand the striated muscle cells in both the skeletal muscle and the heart can undergo only hypertrophy because adult muscle cells have a limited capacity to divide. Therefore, the chiseled physique of the avid weightlifter stems solely from the hypertrophy of individual skeletal muscles.

• An example of pathologic cellular hypertrophy is the cardiac enlargement that occurs with hypertension or aortic valve disease

The mechanisms driving cardiac hypertrophy involve at least two types of signals: mechanical triggers, such as stretch, and trophic triggers, which typically are soluble mediators that stimulate cell growth, such as growth factors and adrenergic hormones. These stimuli turn on signal transduction pathways that lead to the induction of a number of genes, which in turn stimulate synthesis of many cellular proteins, including growth factors and structural proteins. The result is the synthesis of more proteins and myofilaments per cell, which increases the force generated with each contraction, enabling the cell to meet increased work demands. There may also be a switch of contractile proteins from adult to fetal or neonatal forms. For example, during muscle hypertrophy, the α-myosin heavy chain is replaced by the β form of the myosin heavy chain, which produces slower, more energetically economical contraction.

Whatever the exact mechanisms of hypertrophy, a limit is reached beyond which the enlargement of muscle mass can no longer compensate for the increased burden. When this happens in the heart, several “degenerative” changes occur in the myocardial fibers, of which the most important are fragmentation and loss of myofibrillar contractile elements. The variables that limit continued hypertrophy and cause the regressive changes are incompletely understood. There may be finite limits of the vasculature to adequately supply the enlarged fibers, of the mitochondria to supply adenosine triphosphate (ATP), or of the biosynthetic machinery to provide the contractile proteins or other cytoskeletal elements. The net result of these changes is ventricular dilation and ultimately cardiac failure, a sequence of events that illustrates how an adaptation to stress can progress to functionally significant cell injury if the stress is not
relieved.