Porth's Essentials of Pathophysiology, 4e

n their simplest form, all diseases exert their effects on the smallest living unit of the body—the cell. When confronted with stresses that endanger its normal struc- ture and function, the cell undergoes adaptive changes that permit survival and maintenance of function. It is only when the stress is overwhelming or adaptation is ineffective that injury, maladaptive changes, and cell death occur. Biologic aging produces its own changes in cell structure and function. Cellular Responses to Stress, Injury, and Aging 2 C h a p t e r I

Cellular Responses to Persistent Stress Adaptations of Growth and Differentiation Atrophy

Hypertrophy Hyperplasia Metaplasia Dysplasia

Intracellular Accumulations Pathologic Calcifications

Dystrophic Calcification Metastatic Calcification Cell Injury, Death, and Senescence Causes of Cell Injury Injury from Physical Agents

Radiation Injury Chemical Injury Injury from Biologic Agents Injury from Nutritional Imbalances Mechanisms of Cell Injury

Free Radical Injury Hypoxic Cell Injury Impaired Calcium Homeostasis Reversible Cell Injury and Cell Death Reversible Cell Injury Programmed Cell Death Necrosis Cellular Aging Replicative Senescence Genetic Influences Accumulation of Environmental and Genetic Damage Syndromes of Premature Aging

Cellular Responses to Persistent Stress

Cells adapt to changes in the internal environment just as the total organism adapts to changes in the external environment. Cells may adapt by undergoing changes in size, number, and type. These changes, occurring sin- gly or in combination, may lead to atrophy, hypertro- phy, hyperplasia, metaplasia, and dysplasia (Fig. 2-1). Cellular stresses also include intracellular accumula- tions and storage of products in abnormal amounts. 1,2

Adaptations of Growth and Differentiation

Numerous molecular mechanisms mediate cellular adaptation, including factors in the cellular microen- vironment and the cells themselves. These mechanisms largely depend on extracellular signals and cues, which in turn activate intracellular signaling mechanisms transmitted by chemical messengers that alter gene expression. Once the primary stimulus for adaptation is removed, the cause of changing gene expression patterns is removed and the cell may revert back to its previous state. Whether adaptive cellular changes are normal or abnormal depends in part on whether the response was mediated by an appropriate stimulus. Normal adaptive responses occur in response to need and an appropriate

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