HYPERTROPHY

Hypertrophy represents an increase in cell size and with it an increase in the amount of functioning tissue mass. It re­sults from an increased workload imposed on an organ or body part and is commonly seen in cardiac and skeletal muscle tissue, which cannot adapt to an increase in work­load through mitotic division and formation of more cells. Hypertrophy involves an increase in the functional com­ponents of the cell that allows it to achieve equilibrium be­tween demand and functional capacity. For example, as muscle cells hypertrophy, additional actin and myosin fil­aments, cell enzymes, and adenosine triphosphate (ATP) are synthesized.

Hypertrophy may occur as the result of normal phys­iologic or abnormal pathologic conditions. The increase in muscle mass associated with exercise is an example of physiologic hypertrophy. Pathologic hypertrophy occurs as the result of disease conditions and may be adaptive or compensatory. Examples of adaptive hypertrophy are the thickening of the urinary bladder from long-continued obstruction of urinary outflow and the myocardial hyper­trophy that results from valvular heart disease or hyper­tension. Compensatory hypertrophy is the enlargement of a remaining organ or tissue after a portion has been surgi­cally removed or rendered inactive. For instance, if one kidney is removed, the remaining kidney enlarges to com­pensate for the loss.

The precise signal for hypertrophy is unknown. It may be related to ATP depletion, mechanical forces such as stretching of the muscle fibers, activation of cell degrada­tion products, or hormonal factors.¹ Whatever the mech­anism, a limit is eventually reached beyond which further enlargement of the tissue mass is no longer able to com­pensate for the increased work demands. The limiting factors for continued hypertrophy might be related to lim­itations in blood flow. In hypertension, for example, the increased workload required to pump blood against an elevated arterial pressure results in a progressive increase in left ventricular muscle mass and need for coronary blood flow (Fig. 5-2).

There has been recent interest in the signaling path­ways that control the arrangement of contractile elements in myocardial hypertrophy. Research suggests that certain signal molecules can alter gene expression, controlling the size and assembly of the contractile proteins in hyper-trophied myocardial cells. For example, the hypertrophied

CHAPTER 5 Cellular Adaptation, Injury, and Death

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5-2 Myocardial hypertrophy. Cross-section of the heart in a patient with long-standing hypertension. (From Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 9]. Philadelphia: Lippincott-Raven)

myocardial cells of well-trained athletes have proportional increases in width and length. This is in contrast to the hypertrophy that develops in dilated cardiomyopathy, in which the hypertrophied cells have a relatively greater in­crease in length than width. In pressure overload, as oc­curs with hypertension, the hypertrophied cells have greater width than length.³ It is anticipated that further elucida­tion of the signal pathways that determine the adaptive and nonadaptive features of cardiac hypertrophy will lead to new targets for treatment.