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Abnormal cellular growth may result in either a decrease or an increase in the mass of the involved tissue (see Figure 16-4).
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Atrophy is a decrease in the size of a tissue or organ, resulting from a decrease either in the size of individual cells or in the number of cells composing the tissue. Note that atrophy, which is a decrease in size of a normally formed organ, is distinct from agenesis, aplasia, and hypoplasia, which are abnormalities of organ development.
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Hypertrophy is an increase in the size of a tissue due to increased size of individual cells (Table 16-2). It occurs in tissues made up of permanent cells, in which a demand for increased metabolic activity cannot be met through cell multiplication.
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Hyperplasia is an increase in the size of a tissue as a result of increased numbers of component cells (Table 16-2). It is the principal mechanism accounting for increased size in tissues composed of labile and stable cells.
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Not uncommonly, increased size of a tissue is due to a combination of hypertrophy and hyperplasia.
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Decrease in the size of a cell results from a reduction in the amount of cytoplasm and the number of cytoplasmic organelles; it is usually associated with diminished metabolism. Degenerating organelles are taken up in lysosomal vacuoles for enzymatic degradation (autophagy). Residual organelle membranes often accumulate in the cytoplasm as brown lipofuscin pigment. A decrease in cell number results from an imbalance of cell proliferation and death over a long period.
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Atrophy of disuse occurs in immobilized skeletal muscle and bone, as when a fractured limb is put in a cast or when a patient is restricted to complete bed rest. Skeletal muscle atrophies rapidly with disuse. Initially, there is a rapid decrease in cell size that is readily reversible when activity is resumed. With more prolonged immobilization, muscle fibers decrease in number as well as in size. Because skeletal muscle can regenerate only to a very limited extent, restoration of muscle size after loss of muscle fibers can only occur through compensatory hypertrophy of the surviving fibers, which often requires a long rehabilitation period. Bone atrophy results when bone resorption occurs more rapidly than bone formation; it is characterized by decreased size of the trabeculae (decreased mass), leading to osteoporosis of disuse.
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Skeletal muscle is dependent on its nerve supply for normal function and structure. Damage to the lower motor neuron at any point between the cell body in the spinal cord and the motor end plate leads to rapid atrophy of the muscle fibers supplied by that nerve. When denervation is temporary, physical therapy and electrical stimulation of the muscle are important to prevent muscle fiber loss and ensure that normal function can be restored when nerve function is reestablished. Many primary muscle diseases (eg, the genetically determined dystrophies) also show irregular atrophy of muscle fibers.
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Atrophy Due to Loss of Trophic Hormones
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The endometrium, breast, and many endocrine glands are dependent on trophic hormones for normal cellular growth, and withdrawal of these hormones leads to atrophy. When estrogen secretion by the ovary decreases at menopause, there is physiologic atrophy of the endometrium, vaginal epithelium, and breast. Pituitary disease associated with decreased secretion of pituitary trophic hormones results in atrophy of the thyroid, adrenals, and gonads. High-dose adrenal corticosteroid therapy, which is sometimes used for immunosuppression, causes atrophy of the adrenal glands because it suppresses pituitary corticotropin (adrenocorticotropic hormone [ACTH]) secretion. Such patients soon lose the ability to secrete cortisol and become dependent on exogenous steroids. Withdrawal of steroid therapy in such patients must be gradual enough to permit regeneration of the atrophied adrenal.
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Atrophy Due to Lack of Nutrients
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Severe protein-calorie malnutrition (marasmus) results in the utilization of body tissues such as skeletal muscle as a source of energy and protein after other sources such as adipose stores have been exhausted. Marked muscle atrophy is seen in marasmus.
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A decrease in blood supply (ischemia) to a tissue as a result of arterial disease results in atrophy of the tissue due to progressive cell loss. Cerebrovascular disease, for example, is associated with cerebral atrophy, including neuronal loss.
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Cell loss is one of the morphologic changes of the aging process. It is most apparent in tissues populated by permanent cells, eg, the brain and heart. Atrophy due to aging is frequently compounded by atrophy due to coexisting factors such as ischemia.
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Prolonged compression of tissue causes atrophy. A large, encapsulated benign neoplasm in the spinal canal may produce atrophy in both the spinal cord it compresses and the surrounding vertebrae. It is likely that such atrophy results from compression of small blood vessels, resulting in ischemia, and not from the direct effect of pressure on cells.
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Causes of Hypertrophy & Hyperplasia
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Hypertrophy results from increased amounts of cytoplasm and cytoplasmic organelles in cells. In secretory cells, the synthetic apparatus—including the endoplasmic reticulum, ribosomes, and the Golgi zone—becomes prominent. In contractile cells such as muscle fibers, there is an increase in size of cytoplasmic myofibrils. Hyperplasia results when cells of a tissue are stimulated to undergo mitotic division, thereby increasing the number of cells.
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Physiologic Hypertrophy and Hyperplasia
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Hypertrophy and hyperplasia may occur as an adaptation to increased demand (Table 16-2; Figures 16-1, 16-2, and 16-3). Hypertrophy and hyperplasia are controlled responses reflecting increased demand; if the demand is removed, the tissues revert toward normal.
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Pathologic Hypertrophy and Hyperplasia
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Abnormal hypertrophy and hyperplasia occur in the absence of an appropriate stimulus of increased functional demand. Myocardial hypertrophy, if it occurs without recognizable cause (eg, in the absence of hypertension or valvular or congenital heart disease), is considered an example of pathologic hypertrophy. Such hypertrophy is frequently associated with abnormal cardiac function, producing cardiomyopathy (Chapter 23: The Heart: III. Myocardium & Pericardium).
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Endometrial hyperplasia is an important result of increased estrogen stimulation, particularly when estrogens are not opposed by progesterone secretion, as typically occurs near menopause. It is associated with irregular, often excessive uterine bleeding (Chapter 53: The Uterus, Vagina, & Vulva). The presence of excessive trophic hormones causes hyperplasia of the target organs, eg, excessive secretion of ACTH causes bilateral adrenal hyperplasia. The hyperplastic target organs frequently show increased function. In the case of the adrenal gland, there is increased cortisol secretion (Cushing's syndrome; Chapter 60: The Adrenal Cortex & Medulla).
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Thyroid hyperplasia (goiter; Graves' disease) results from increased thyroid-stimulating hormone (TSH) stimulation of the thyroid or from the action of autoantibodies that are able to bind to TSH receptors in thyroid cell membranes (Chapter 58: The Thyroid Gland).
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Hyperplasia of the prostategland is common in older men and is due to hyperplasia of both the glandular and the stromal elements. The cause is not known, although it is believed that waning androgen levels may be responsible (Chapter 51: The Testis, Prostate, & Penis).