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8/12/2019 Cellular Injury & Adaptations
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The normal cell is confined to a fairlynarrow range of function and structure
by its state of metabolism, differentiation,specialization & is able to handlephysiologic demands, maintaining asteady state called homeostasis.
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Adaptationsare reversible functionaland structural responses to more severe
physiologic stresses and somepathologic stimuli, during which new butaltered steady states are achieved,allowing the cell to survive and continue
to function
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Nature of Injurious Stimulus CELLULAR RESPONSE
ALTERED PHYSIOLOGICAL STIMULI; SOME
NONLETHAL INJURIOUS STIMULI
CELLULAR ADAPTATIONS
Increased demand, increasedstimulation (e.g., by growth factors,hormones)
Hyperplasia, hypertrophy
Decreased nutrients, decreasedstimulation
Atrophy
Chronic irritation (physical or chemical) Metaplasia
Cellular Responses to Injury
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REDUCED OXYGEN SUPPLY; CHEMICALINJURY; MICROBIAL INFECTION
CELL INJURY
Acute and transient Acute reversible injuryCellular swelling fatty change
Progressive and severe (including DNAdamage)
Irreversible injury cell deathNecrosisApoptosis
METABOLIC ALTERATIONS, GENETIC ORACQUIRED; CHRONIC INJURY
INTRACELLULAR ACCUMULATIONS;CALCIFICATION
CUMULATIVE SUBLETHAL INJURY OVERLONG LIFE SPAN
CELLULAR AGING
Cellular Responses to Injury
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HYPERTROPHY
HYPERPLASIA
METAPLASIA
ATROPHY
HYPOPLASIA
DYSPLASIA
APLASIA, AGENESIS
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Increase in size of organs and cells
hypertrophied organ has no new cells, just larger
cells. The increased size of the cells is due to the
synthesis of more structural components of the cells
Response to increased work load (cardiac, skeletal
muscle) or hormonal stimulation (uterine muscle)
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Hypertrophy can be
physiologicor
pathologic
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It is caused by 1- increased functional demand or 2- by stimulation by hormones and growth
factors. Example The striated muscle cells in skeletal
muscles have only a limited capacity fordivision, and respond to increased metabolicdemands mainly by undergoing hypertrophy.
The most common stimulus for hypertrophy ofmuscle is increased workload. For example,the bulging muscles of bodybuilders result froman increase in size of the individual musclefibers in response to increased demand.
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The massive physiologic growth of the uterusduring pregnancy is a good example ofhormone-induced increase in the size of an
organ that results mainly from hypertrophy ofmuscle fibers.
The cellular enlargement is stimulated byestrogen hormoneacting on smooth muscleestrogen receptors, eventually resulting inincreased synthesis of smooth muscle proteinsand an increase in cell size.
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In the heart, the stimulus for hypertrophy is
usually chronic hemodynamic overload,
resulting from either hypertension or faulty
valves. In both tissue types the muscle cells
synthesize more proteins and the number of
myofilaments increases. This increases the
amount of force each myocyte cangenerate, and thus increases the strength
and work capacity of the muscle as a
whole.
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Mechanisms of Hypertrophy
Hypertrophy is the result of increased
production of cellular proteins
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Hyperplasia is an increase in the numberof cells in an organ or tissue, usually
resulting in increased mass of the organor tissue.
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Although hyperplasia and hypertrophyare distinct processes, frequently they
occur together, and they may betriggered by the same external stimulus.
Hyperplasia takes place if the cellpopulation is capable of dividing, andthus increasing the number of cells.
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Hyperplasia can be
physiologic or
pathologic.
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Physiologic hyperplasia can be dividedinto:
(1) hormonal hyperplasia, (2) compensatory hyperplasia,
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(1) hormonal hyperplasia, whichincreases the functional capacity of atissue when needed,
Hormonal hyperplasia is well illustratedby the proliferation of the glandularepithelium of the female breast at
puberty and during pregnancy, usuallyaccompanied by enlargement(hypertrophy) of the glandular epithelialcells.
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(2) compensatory hyperplasia, whichincreases tissue mass after damage or
partial resection. partial hepatectomy have been very
useful for defining the mechanisms thatstimulate regeneration of the liver
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Most forms of pathologic hyperplasia are caused byexcesses of hormones or growth factorsacting on targetcells.
Endometrial hyperplasia is an example of abnormal
hormone-induced hyperplasia. Normally, after amenstrual period there is a rapid burst of proliferativeactivity in the epithelium that is stimulated by pituitaryhormones and ovarian estrogen. It is brought to a halt bythe rising levels of progesterone, usually about 10 to 14days before the end of the menstrual period. In someinstances, however, the balance between estrogen andprogesterone is disturbed. This results in absolute orrelative increases in the amount of estrogen, withconsequent hyperplasia of the endometrial glands. Thisform of pathologic hyperplasia is a common cause ofabnormal menstrual bleeding
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Benign prostatic hyperplasia is anothercommon example of pathologichyperplasia induced in responses to
androgen hormones. pathologic hyperplasia constitutes a fertile
soil in which cancerous proliferation mayeventually arise. For instance, patients with
hyperplasia of the endometrium are atincreased risk for developing endometrialcancer.
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viral infections, such as papillomaviruses, whichcause skin warts and several mucosal lesionscomposed of masses of hyperplastic epithelium.
Here, growth factors produced by viral genes or byinfected cells may stimulate cellular proliferation
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Hyperplasia is the result of growth factordriven proliferation of mature cells and,
in some cases, by increased output ofnew cells from tissue stem cells
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Cells capable of division may respond to stress by
undergoing both hyperplasia and hypertrophy,
whereas in nondividing cells(e.g., myocardial
fibers) increased tissue mass is due to hypertrophy.
In many organs hypertrophy and hyperplasia may
coexist and contribute to increased size.
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Atrophy is reduced size of an organ ortissue resulting from a decrease in cell
size and number.
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Atrophy can be
physiologic or
pathologic.
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Physiologic atrophyis common duringnormal development.
Some embryonic structures, such asthyroglossal duct, undergo atrophyduring fetal development.
The uterus decreases in size shortly afterparturition, and this is a form ofphysiologic atrophy.
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Decreased workload (atrophy of disuse).When a fractured bone is immobilized in aplaster cast or when a patient is restricted to
complete bed rest, skeletal muscle atrophyrapidly ensues. The initial decrease in cellsize is reversible once activity is resumed.
With more prolonged disuse, skeletalmuscle fibers decrease in number (due to
apoptosis) as well as in size; this atrophycan be accompanied by increased boneresorption, leading to osteoporosis ofdisuse.
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Loss of innervation (denervationatrophy). The normal metabolism and
function of skeletal muscle aredependent on its nerve supply. Damageto the nerves leads to atrophy of themuscle fibers supplied by those nerves
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Diminished blood supply. A decrease inblood supply (ischemia) to a tissue as aresult of slowly developing arterialocclusive disease results in atrophy ofthe tissue.
In late adult life, the brain may undergo
progressive atrophy, mainly because ofreduced blood supply as a result ofatherosclerosis.This is calledsenileatrophy; it also affects the heart.
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Inadequate nutrition. Profound protein-caloriemalnutrition (marasmus) is associated with theuse of skeletal muscle as a source of energyafter other reserves such as adipose storeshave been depleted. This results in markedmuscle wasting
Cachexia is also seen in patients with chronicinflammatory diseases and cancer. In theformer, chronic overproduction of theinflammatory cytokine tumor necrosis factor(TNF) is thought to be responsible for appetitesuppression and lipid depletion, culminating inmuscle atrophy.
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Loss of endocrine stimulation. Manyhormone-responsive tissues, such as the
breast and reproductive organs, aredependent on endocrine stimulation fornormal metabolism and function. Theloss of estrogen stimulation after
menopause results in physiologicatrophy of the endometrium, vaginalepithelium, and breast.
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Pressure.Tissue compression for anylength of time can cause atrophy. Anenlarging benign tumor can cause
atrophy in the surrounding uninvolvedtissues.
Atrophy in this setting is probably the
result of ischemic changes caused bycompromise of the blood supply by thepressure exerted by the expandingmass.
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Atrophy results from decreased proteinsynthesis and increased protein
degradation in cells. Protein synthesis decreases because of
reduced metabolic activity.
The degradation of cellular proteinsoccurs mainly by the ubiquitin-
proteasome pathway.
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Metaplasiais a reversible change inwhich one differentiated cell type
(epithelial or mesenchymal) is replacedby another cell type.
It may represent an adaptive substitutionof cells that are sensitive to stress by cell
types better able to withstand theadverse environment.
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The most common epithelial metaplasiais columnartosquamousas occurs in
the respiratory tract in response tochronic irritation.
In the habitual cigarette smoker, thenormal ciliated columnar epithelial cells
of the trachea and bronchi are oftenreplaced by stratified squamousepithelial cells.
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Stones in the excretory ducts of the salivaryglands, pancreas, or bile ducts may also causereplacement of the normal secretory columnarepithelium by stratified squamous epithelium.
A deficiency of vitamin A (retinoic acid)induces squamous metaplasia in therespiratory epitheliuM. In all these instances themore rugged stratified squamous epithelium isable to survive under circumstances in whichthe more fragile specialized columnarepithelium might have succumbed. However,the change to metaplastic squamous cellscomes with a price
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In the respiratory tract, for example,although the epithelial lining becomestough, important mechanisms of
protection against infection
mucussecretion and the ciliary action of thecolumnar epitheliumare lost.
Thus, epithelial metaplasia is a double-edged sword and, in mostcircumstances, represents anundesirable change.
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Moreover, the influences that predisposeto metaplasia, if persistent, may initiate
malignant transformation in metaplasticepithelium. Thus, a common form ofcancer in the respiratory tract iscomposed of squamous cells, which
arise in areas of metaplasia of thenormal columnar epithelium intosquamous epithelium.
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Metaplasia from squamous to columnartypemay also occur, as in Barrett
esophagus, in which the esophagealsquamous epithelium is replaced byintestinal-like columnar cells under theinfluence of refluxed gastric acid.
Cancers may arise in these areas; theseare typically glandular(adeno)carcinomas
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is the result of a reprogramming of stemcells that are known to exist in normal
tissues, or of undifferentiatedmesenchymal cells present inconnective tissue. In a metaplasticchange, these precursor cells
differentiate along a new pathway
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Change in cellular organization, size and organ
architecturealmost always used to describe
changes in epithelium
Response to irritation and damage (classic
example is Pap smear)
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Aplasia, Agenesis
Developmental defects; result of genetic defect
or in uterodeficiency (i.e. folate)