31
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
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
I
Cellular
Responses to
Stress, Injury,
and Aging
2
C h a p t e r
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
