cellular injury & adaptations

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)

cellular injury & adaptations

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