Tissue and Cellular Injury

8/12/2019 Tissue and Cellular Injury

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Chapter 1

Tissue and Cellular Injury


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1. Overview of cellular responses to stress and

noxious stimuli

(1)Cells are active participantsin their

environment, constantly adjustintheir

structure and function to accommodatechanin demands and extracellular stresses.

(!)Cells tend to maintain their intracellular

milieuwithin a fairly narrow raneofphysioloic parameters, that is, they maintain

normal physioloic state (homeostasis).


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(")#hen cells meet physioloic stresses or

patholoic stimuli, they can underoadaptation, achievin a new steady state

and preservin via$ility and function.

(%)The cellular principal adaptive

responses are hyperplasia, hypertrophy,

atrophy, and metaplasia. e. &iceps'pectoral muscle hypertrophy.


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()If the adaptive capa$ility is exceeded or if

the external stress is inherently harmful,cell injurydevelops (i. 1).

(*)#ithin certain limitsinjury is reversible,and cells can return to a sta$le $aseline+

severe or persistent stress results in

irreversible injuryand death of the affectedcells.
http://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Reactive_oxygen_species


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i. 1 taes in the cellular response to stress and injurious stimuli
http://en.wikipedia.org/wiki/Oxidative_stresshttp://en.wikipedia.org/wiki/Oxidative_stress


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(-) Outline(-) Outline

Cellular /daptation

hyperplasia+

hypertrophy+

atrophy+

metaplasia.

Cellular Injury

reversi$le injury

irreversi$le injury

necrosis 0

apoptosis


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Section 1Cellular Adaptation


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Overview: Cellular adaptations tostress

ven under normal conditions, cells mustconstantly adaptto microenvironment

chanes.

/daptations are reversi$le chanesin the

num$er, si2e, phenotype, meta$olic activity,or functionsof cells in response to chanes intheir environment.


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3hysioloic adaptationsusually represent the

cellular responses to normal stimuli $y

hormones or endoenous chemical mediators

e., the hormone4induced enlarement of the

$reast and uterus durin prenancy.

3atholoic adaptationsare responses to stress

that allow cells to modulate their structure and

function and thus escape injury. uchadaptations can ta5e several distinct forms.


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There are numerous types of cellular adaptations

ome involveup or down reulation of specificcellular receptors involved in meta$olism of

certain components.

Others are associated withthe induction ofnew protein synthesis $y the taret cell.

Other adaptationsinvolve a switch $y cells

from producin one type of a family of proteins toanother or mar5edly overproducin one protein.


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Then cellular adaptation is a state that

lies intermediate $etween the normal,

unstressed cell and the injured,

overstressed cell.

Cellular adaptations have many types /trophy( decrease in cell si2e)

6ypertrophy( increase in cell si2e)

6yperplasia( increase in cell num$er)

7etaplasia(chane in cell type)


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mitosishyperplasiahyperplasia

atrophyatrophy

hypertrophyhypertrophy

ORGAN

SI!


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1.6yperplasia

(1) 8efinition Cellular num$er

increasein an

oran'tissue.which may thenwhich may then

have increasedhave increased

volume.volume.

inactive mammary glandLactation breast


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(2) Types:

Physiologic hyperplasiaPhysiologic hyperplasia::Hormonal hyperplasia,

e.. &reast ep. hyperplasia at pu$erty'

prenancy.

Compensatory hyperplasia :9esponse to

deficiency.

e.. 6yperplasia followin surical removal ofpart of liver or one of 5idney+

6yperplasia of the $one marrow in

anemia.


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Pathologic hyperplasiaPathologic hyperplasia caused $ycaused $y

excessive hormonal or rowth factorexcessive hormonal or rowth factor

stimulationstimulation.

e.. Ovarian tumor may produce estroen

and stimulate endometrial hyperplasia+ 3ancreatic islet hyperplasia in infants of

a dia$etic mother (stimulated $y hih

lucose level) +


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:otice

:eoplastic hyperplasia is the total loss ofnormal rowth4differentiation control

mechanism.

6yperplasia is also an important response

of connective tissue cells in wound healin,

in which proliferatin fi$ro$lasts and $lood

vessels aid in repair.


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(") 7echanisms

7ost forms ofpatholoichyperplasia are

due to excessive

hormonal

stimulation or the

effects of GFon

taret cells.

Hyperplasia of prostate gland

Normal prostate gland


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!. 6ypertrophy

(1) 8efinition

/n increase in the

si2e of cells andconse;uently an

increase in the si2e

of the oran.S"eletal muscle

normal

hypertrophy


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(!) Types 6ypertrophy can $e physioloic or patholoic

and is caused either $y specific hormonal

stimulation or $y increased functional demand.

1) 3hysioloic


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3hysioloic hypertrophy of the uterus durin prenancy./,

=ross appearance of a normal uterus (right)and a ravid uterus(left)that was removed for postpartum $leedin. &,mall

spindle4shaped uterine 7Cs from a normal uterus. Compare

this with (C)lare, plump hypertrophied 7Csfrom a ravid

uterus (& and C, same manification).


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!) 3atholoic

Overload, hormone or =

stimulation.

. the cardiac enlarementin hypertension or aortic valve

disease, >left ventricular

hypertrophy7uscle wall is over !cm and

the thic5ness of

interventricular septum

increase+ventually, it is no loner a$le

to compensate for the

increased $urden, and

cardiac failure ensues.


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#yocardial hypertrophy#yocardial hypertrophy

Normal


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(") 7echanisms of hypertrophy(") 7echanisms of hypertrophy

In hypertrophy, there are no new cell, just$ier cell, enlared $y an increased

synthesis of structural proteins and

oranelles.The mechanisms drivin cardiac

hypertrophy involve at least two type of

sinals mechanical triers, such asstretch, and trophic trier, such as

activation of ?4adreneric receptors.


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:otice

Hypertrophy & hyperplasiaare two distinct

processes, $ut they can also occur toether, ando$viously $oth result in an enlared

(hypertrophic)oran.

e.. The lare uterusin prenancy occurs as aconse;uence of estroen4stimulated47C

hypertrophy and hyperplasia.

In contrast, the striated muscle cellscan undero

only hypertrophyin response to increased

demand (overload) $ecause in the adult they

have limited capacity to divide.


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Hyperplasia is characteri2ed $y an increase in cell

num$er.

In pure hypertrophythere are no new cells, just

$ier cells, enlared $y an increased amount ofstructural proteins and oranelles.

Hyperplasia is an adaptive response in cellscapa$le of replication, whereas hypertrophyoccurs

when cells are incapa$le of dividin.


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Normal trophy


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(!) Types

1) 3hysioloice. ain+

shrin5in $reast afterlactation+ uterus after

delivery or in old ae.

!) &lood supply@O!'nutrients@

") Aoss of nerve stimulus

9eflex 'meta$olic activities

reduced. e. nerveinterruptB muscles atrophy

(anterior poliomyelitis ).


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%) ndocrine deficiency7a5e meta$olic activity

reduce. e. pituitary deficiency or hemorrhae or

necrosisB thyroid'adrenals 'onads and enitalorans atrophy.

) Inade;uate nutritione. amine Boran atrophy.

*) 3ressurean enlared tumor can cause atrophy inthe surroundin compressed tissue

-) 8isuse atrophy8emand reduction for nutrition.

e. s5eletal muscle fi$er decrease in num$er as well

as in si2e when a patient is restricted to complete

$ed rest.


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/trophy. &, :ormal $rain of a youn adult./, /trophy of the$rain in an !4year4old male with atherosclerotic disease.

/trophy of the $rain is due to ain and reduced $lood supply.

:ote that loss of $rain su$stance narrows the yri and widens

the sulci.


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Normal myocardial!"## $yocardial trophy!"##


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atrophy of cardiac muscle

lipofuscin


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%&eletal m'scle


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$ressure atrophy of "idney

(pelviectasis of hydronephrosis)

vol'me eight


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(") 7echanisms of atrophy

/trophy represents a reduction in the

structural components of the cell.

This process are varied $ut ultimately

affect the $alance $etween synthesisand

deradation.

8ecreased synthesis, increased

cata$olism, or $oth may cause atrophy.


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:otice

a. /lthouh the atrophic cell si2e ets small and

their function ets low, they are not dead and

reversi$le.

$. /trophy represents a reduction in the structural

components of the cell.The cell contains fewer mitochondria,

endoplasmic reticulum, and increasin in the

num$er of autophaic vacuoles.c. /trophy results from decreased protein synthesis

and increased protein deradation in cells.


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d. The fundamental cellular chanes of atrophy

($oth physioloic and patholoic) are identical.

e. /trophy implies that a new $alance is achieved

$etween cell si2e and diminished $lood supply,

nutrition, or trophic stimulation.

f. ome cellular de$ris within the autophaic

vacuole may resist diestion and persist as

mem$rane $ound residual $odies in the

cytoplasm. #hen present in sufficient amounts,they cause a $rown discoloration to the tissue,

e. myocardium $rown atrophy (Aipofuscin).


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%. 7etaplasia

(1) 8ef. One adult cell type(epithelial or

mesenchymal) is replaced $y another adult

cell type.

It may represent an adaptive su$stitution of

cells that $etter a$le to withstand the

adverse environment.

It is thouht to arise $y enetic

DreproramminD of stem cells.

pithelial and mesenchymal metaplasia.


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(!) Causes

1) Chanes in environment

e.. tones in $ile duct and ureter lead tochane from columnar4ep. into s;uamous

ep.

!) Inflammation e.. In lon ciarettes smo5er, the columnar

ciliated ep. of trachea'$ronchi replaced $y

stratified s;uamous ep. focally or widely. Chronic atrophic astritis astric mucosa

ep. replaced $y intestine mucosa ep. (o$let

cell).


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(")inificance pithelial metaplasia is a two4ededsword.

1) The function is lost (7ucus'sputum can cleandust).

!) Aead to tumorienesis (esp. s;uamous cell

carcinoma).

(%) :otice

7etaplasia may also occur in mesenchymal

cells. e. $one or cartilae metaplasia in fi$rousct. This occurs particularly in the foci of injury.


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$etaplasia of normal col'mnar (left) to s*'amo's epitheli'm (right)

in a bronch's+ shon () schematically and (,) histologically

The s;uamous metaplasia of tracheaThe s;uamous metaplasia of trachea


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Normal bronch's m'cosa HE pse'dostratifiedcol'mnar ciliated ep.

The s;uamous metaplasia of tracheaThe s;uamous metaplasia of trachea

or $ronchi columnar epitheliumor $ronchi columnar epithelium


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;uamous metaplasia of trachea '$ronchi mucosa

columnar ep. and the lamina propria hyperemia. 6


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mesenchymal metaplasiamesenchymal metaplasia


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mesenchymal metaplasiamesenchymal metaplasia


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u$cellular responses to adaptation

Includin the chanes oflysosome

endoplasmic reticulum,

the mitochondrial

cytos5eletal a$normalities, etc.


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ummary

Hyperplasia:increased cell num$ers in response

to hormones and other =s+ occurs in tissues

whose cells are a$le to divide.

Hypertrophy:increased cell and oran si2e, often

in response to increased wor5load+ induced $y

mechanical stress and $y =s+ occurs in tissuesincapa$le of cell division.


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Atrophy:decreased cell and oran si2e, as a result

of decreased nutrient supply or disuse+ associated

with decreased synthesis and increased proteolytic

$rea5down of cellular oranelles.

etaplasia:chane in phenotype of differentiated

cells, often a response to chronic irritation that

ma5es cells $etter a$le to withstand the stress+

usually induced $y altered differentiation pathway oftissue stem cells+ may result in reduced functions or

increased propensity for malinant transformation.

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Tissue and Cellular Injury