CELL INJURY: CAUSES OF CELL INJURY, MECHANISMS OF REVERSIBLE AND IRREVERSIBLE CELL INJURY.

CELL INJURY.

Causes of cell injury range from gross mechanical external causes to mild endogenous causes as genetic lack of enzymes etc.
Virtually all forms of tissue injuries start with molecular or structural alterations in cells. Under normal conditions, the cells are in: homeostastatic stea!"# state Normal cell is confined to relatively narrow range of functions and structure y its genetic !rogramme to handle normal !hysiologic demands. Cells react to adverse influence y "# ada!ting $# sustaining reversi le injury %# suffering irreversi le cellular injury# cell death &ore excessive stimuli 'either !hysiologic or !athologic( may cause cellular ada!tation #in order to reach a$te%e! stea!" state # for exam!le, excessive work stress causes an increase in muscle mass that reflects the increase in size of the individual muscle fi er, results in higher level of meta olic activity )and new e*uili rium is reached# h"&e%t%o&h" # on the other hand# at%o&h"# is ada!tative res!onse in which there is a decrease in the size and function of the cells# and results from a slow long#lasting decrease of lood su!!ly if the limits of ada!tative mechanisms are exceeded or when no ada!tative res!onse is !ossi le# ce$$ i'()%"

Re*e%si+$e ce$$ i'()%" denotes !athologic changes that can e reversed when the stimulus is removed and the cellular injury has een mild. Cell injury is reversi le only u! to certain !oint. I%%e*e%si+$e ce$$ i'()%" denotes !athologic changes that are !ermanent and cause cell death, they cannot e reversed to normal state

for exam!le: if the lood su!ly to heart muscles is cut off for "+#", minutes# the myocardial cell ex!eriences injury ut it can recover to normal function, if the lood flow is cut off for longer !eriod# the myocardial fi er dies#necrosis

CAUSES OF CELL INJURY

H"&o,ia injury

'- decrease of oxygen su!!ly( #most common cause of cell

#occurs usually as a result of ischemia '- loss of lood su!!ly(, which occurs for exam!le when arterial flow suffers from atherosclerosis or throm otic occlusion of arteries # most common cause of hy!oxia #is due to inade*uate oxygenation, for exam!le in cardiores!iratory failure #is caused y loss of oxygen#carrying ca!acity of the lood, either due to a'emia 'decreased ca!acity of the lood for oxygen(, or after !oisoning with car on monoxide 'C.(- loss of the carrying ca!acity of the lood de!ending on the severity of hy!oxia# the cell may undergo #ada!tation #injury #cell death for exam!le: #if femoral artery is narrowed 'due to atherosclerotic or atherothrom otic reduction of the lumen of the affected vessel(# skeletal muscles of the leg decrease in size- atro!hy. /his reduction in size of cell mass may achieve a new alance on the lower level, ut severe and !rolonged hy!oxia will induce severe injury and cell death.

&h"sica$ a-e'ts # many forms of !hysical energy may give rise to cell and tissue injury, such as mechanical trauma, extremes of tem!erature, sudden changes in atmos!here !ressure, electromagnetic energy, radiation and electric shock

/he most im!ortant and fre*uent in clinical !ractice are conse*uences of mechanical forces 'traffic accidents(. Changes in atmos!here !ressure and hy!otermia are relatively uncommon causes of injury, ut hy!ertermia ' urns( are encountered more often. 0adiation injury# have also assumed im!ortance as !otential causes of wides!read destruction

chemica$ a-e'ts #the list of chemicals that may cause cell and tissue injury includes
#!oisons#arsenic, cyanide, mercuric salts,etc #air !ollutants #insecticides and her icides #alcohol, narcotic drugs

#variety of concentrations

thera!eutic

drugs

and

even

oxygen

in

high

i'.ectio)s a-e'ts# these agents range from the su microsco!ic viruses, rickettsiae to acteria, fungi and higher forms of !arasites. imm)'o$o-ic %eactio's #immune system works in a defense against iologic agents. 1mmune reactions may, however cause cell injury
#first# so called 2ana!hylactic reaction3 # to a foreign !rotein or

drug

#second# reactions to endogenous 2self#antigens3 are res!onsi le for a num er of so called 2 autoimmune diseases3

-e'etic !e%a'-eme'ts#genetic defects cause a num er of diseases

4enetic injury may result in severe defects and congenital malformations '5owns syndrome( or in mild derangements and errors of meta olism 'lack of a distinctive enzyme (, etc.

')t%itio'a$ !is+a$a'ces# even now nutritional errors continue to e major cause of cell injury.
#!rotein#calorie !o!ulation

deficiencies#

chiefly

among

under!rivileged

#deficiencies of s!ecific vitamins #nutritional excesses have ecome im!ortant in cell injury among over!rivileged !o!ulation 'excess in li!ids#!redis!ose to atherosclerosis, cause o esity, influence dia etes mellitus(.

/ENERAL MECHANISMS OF CELL INJURY.

6our intracellular systems are !articularly vulnera le to cell injury: ". maintenance of the integrity of cell mem rane 'u!on which the osmotic homeostasis of the cell is de!endent(

$. aero ic res!iration involving oxidative !hos!horylation and !roduction of 7/8 'mitochondria( %. synthesis of functional and structural !roteins '4olgi( 9. !reservation of the genetic a!!aratus of the cell 'nucleus( Im&o%ta't as&ects o. ce$$ i'()%": #the following factors influence severity of injury, conse*uences of cell injury de!end oth on cell and the injurious agent, and other factors "# wide#s!read effect of changes#whatever the first !oint of injury in the cell is # wide#range secondary effects. 7 ove mentioned four vulnera le systems are closely related, thus injury at one of them leads to wides!read secondary effects

for exam!le#im!airment of aero ic res!iration disru!ts the energy# de!endent sodium !um!# results in loss of ionic and fluid alance# causes alterations in the intracellular content of water and ions# cell swelling $# time factor# mor!hologic changes of cell injury only after some critical time. ecome a!!arent

for exam!le# light microsco!ic changes characteristic of cell death do not occur in the myocardium until "+#"$ hours after total injury# ut irreversi le injury actually occurs within $+#:+ minutes;; %# cell susce!ti ility to injury # reactions of the cells to !athologic stimuli de!end on the ty!e of the cell. /he conse*uences of cell injury de!end on the ty!e, state and ada!ta ility of the cell.

1m!ortant factors in the cell are: #nutritional state, hormonal status, meta olic activity and demands of the cell. <ow vulnera le is the cell when ex!osed to hy!oxia= # high susce!ti ility#neurons '%#, minutes( # intermediate# myocardium, he!atocytes, renal e!ithelial cell '$+#"$+ minutes( # low susce!ti ility# fi ro lasts, e!idermis, skeletal muscles ' many hours( 9# reactions of the cell to !athologic stimuli de!end on the ty!e of injury, its duration, its severity, thus short ischemia may induce reversi le injury, while more !rolonged ischemia might lead either to cell death or to slow irreversi le injury.

 MECHANISMS OF CELL INJURY IN HY0O1IC INJURY. %e*e%si+$e ce$$ i'()%" <y!oxia first causes loss of !hos!horylation in mitochondria# results in decrease of !roduction of energy rich#7/8 # loss of 7/8 'which is a energy source( has wides!read effects on many systems in the cell# for exam!le#heart muscle sto!s to contract within :+ seconds after coronary occlusion 'noncontractility does not mean the cell death( the decrease in cellular 7/8 stimulates increase of anaero ic glycolysisthe other source how to generate energy for the cell glycogen is ra!idly de!leted, glycolysis results in accumulation of lactic acids # it reduces !< intracellularly # at this !oint, there is also early clum!ing of nuclear chromatin energy#de!endent sodium !um! slows down the activity # sodium !um! kee!s normally the concentration of !otassium '>?( significantly higher intracellularly. 6ailure of active trans!ort through the cell mem rane causes that sodium 'Na?( accumulates within the cell and !otassium diffuses out of the cell # it leads to im!ortant movement of water intracellularly-

mor!hologic changes in reversi le cell injury

#cellular swelling #due to accumulation of cata olites of meta olism and water intracellularly #loss of microvilli # le s swelling of cisternae of endo!lasmic reticulum #detachment of ri osomes from the granular @0 due to disru!tions of energy#de!endent interactions etween mem ranes myelin figures# derived from !lasma or from mem ranes of organelles. /hey are thought to results from dissociation of li!o!roteins. 7ll the a ove mentioned changes are reversi le if oxygenation is restored.

i%%e*e%si+$e ce$$ i'()%"

#if ischemia !ersists, irreversi le injury develo!s. 1rreversi le injury is marked y severe mitochondrial vacuolization, extensive damage to !lasma mem ranes, swelling of ri osomes, swelling of ri osomes. 1njury

to lysosomal mem ranes leads to leakage of lysosomal enzymes into the cyto!lasm, there is no universal iochemical !oint of no return, transitions from reversi le injury to cell death. c%itica$ e*e'ts .o% i%%e*e%si+$e ce$$ i'()%": #"# 7/8 de!letion ina ility to reverse mitochondrial dysfunction 'lack of oxidative !hos!horylation and !roduction of energy ( #$# Cell mem rane demage #the earliest !hase of irreversi le injury is associated with functional and structural defects in cell mem ranes #great deal of evidence indicates that cell mem rane damage is a central factor in the !athogenesis of irreversi le injury #intact cell mem ranes are essencial to the maintenance of normal cell !ermea ility and volume# loss of mem rane integrity causes massive influx of calcium from the extracellular s!ace# resulting in mitochondrial dysfunction, inhi ition of intracellular enzymes, denaturation of !roteins 2. CHEMICAL INJURY chemicals induce cell injury y one of two major mechanisms: "#some chemicals act directly molecules or cellular organelles y chemical indings with some critical inds directly to

for exam!le: mercuric chloride !oisoning 'mercury sul!hydryl grou!s of cell mem ranes(##41/ and kidney

or anticancer drugs and some anti iotic drugs also induce cell damage y direct cytotoxic effects #$#other chemicals are not iologically active ut convert into reactive toxic meta olits 'role of free radicals for exam!le( 3. INJURY INDUCED BY VIRUSES viruses induce cellular changes y two general mechanisms: "#cytolytic and cyto!athic viruses cause various degrees of cellular injury and cell death $#oncogenic viruses stimulate host cell to !roliferate and may induce tumors

Cyto!athic effects of viruses cause injury y two major mechanisms: #first is direct cyto!athic effect, in which ra!idly re!licating virus !articles interfere with some as!ects of cell meta olism and cause cellular damage. &ost directly cyto!athic viruses have a high degree of cell s!ecificity*i%a$ t%o&ism, caused y !resence of mem rane rece!tors on host cells, which interact with viral strucutresAallow to attack to the host cellAto enter the host cell and cause the injury y active redu!lication of virus !articles #second mechanism involves the induction of an immunological res!onse#destruction of the cell y either anti ody or cell#mediated reactions, for exam!le the damage and death of he!atocytes caused y he!atitis B viruses are mediated y cytolysis induced y /#lymfocytes /he nature of cell res!onse to viral re!lication de!ends on the host cell and ty!e of virus and can have several forms: "#cell lysis#a!!arently due to ra!id viral re!lication $#some viruses can cause cytoskeletal damage 'for exam!le disru!tion of vimentin( %#cell may res!onse y formation of giant multinucleate cells, due to cell#cell fusion, for exam!le in measles or her!es virus infection 9#some viruses infected cells develo! inclusion odies, which contain virions or viral !roteins in nuclei or cyto!lasm

MOR0HOLO/Y OF CELL INJURY, NECROSIS, A0O04OSIS, IN4RACELLULAR ACCUMULA4IONS, 0I/MEN4S.

Mo%&ho$o-" o. ce$$ i'()%" 5.6 U$t%ast%)ct)%a$ cha'-es include: cellular swelling # it is near#universal manifestation of cell injury formation of cyto!lasmic le s and distortion of microvilli deterioration of cell attachments

mitochondrial changes# occur very ra!idly in ischemic injury, are delayed in some ty!es of chemical injury. early after ischemia# swelling of mitochondrias due to changes in ions

ut

small to large size amor!hous densities in mitochondrias# these consist of li!ids or li!id#!rotein com!lexes# dense granules rich in calcium 'a!!ear early after re!erfusion( endo!lasmic reticulum# changes of @0 occur early after injury due to changes in ion and water regulation # detachment of ri osomes and disaggregation of !olysomes #result in decrease of !roteosynthesis !rogressive fragmentation of @0 # results in formation of 2 myelin figures3 # derived from !lasma and organelle mem ranes 'li!o!roteins( alterations of lysosomes in cell injury6 generally a!!ear later lysosomes ecome swollen, and after the onset of lethal injury lysosomes ru!ture and this event causes leakage of the lysosomal enzymes at this stage- irreversi le cell injury hete%o&ha-"6 is the u!take of materials from the external environment y !hagocytosis. exam!les: !hagocytosis and degradation of acteria y leukocytes, removal of necrotic de ris y macro!hages, rea sor!tion of !rotein a)to&ha-"6 is the !hagocytosis y lysosomes of deteriorating intracellular orgtanelles, including mitochondria and endo!lasmic reticulum. 7uto!hagy is !articularly !ronounced in cells undergoing atro!hy. Cysosomes with undigested de ris# are called auto!hagic vacuoles and may !ersist within the cells as residual odies or may e extruded from the cell

26 Li-ht mic%osco&ic cha'-es. Re*e%si+$e cha'-es#in classic !athology nonlethal injury to cells were termed 2degenerations, dystro!hies3, ut today it is common to designate them 2reversi le injuries3 or 2regressive changes3 two !atterns can e recognized y light microsco!y: 56ce$$)$a% s7e$$i'-# a!!ears whenever the cell is not ca!a le of maintaining ionic and water homeostasis it is near#universal change in cell injury #is the first manifestation of cell injury #it may e sometimes difficult to a!!reciate with the light microsco!y alone, etter evident at the level of organ# grossly: the organ ecomes !aler, it shows an increased turgor, increased weight microsco!ically: enlargment of cells # if water continues to accumulate#small clear vacuoles a!!ear within the cyto!lasm '-distended segment of @0( - hydro!ic change or vacuolar degeneration, for exam!le: e!ithelial cells of renal tu uli

26.att" cha'-e# is more often encountered in the cells involved in fat meta olism, such as he!atocytes # Not so universal reaction as cell swelling. # refers to any a normal accumulation of fat within !arenchymal cells #different mechanisms account for fatty change # later will e discussed #fatty change is most commonly seen in the liver, heart, muscle,etc. #although fatty change is an indicator of nonlethal injury, in many situations is encountered in cells adjacent to those that have died and undergone necrosis

Ce$$ !eath ) is an irreversi le change in the cell associated with its end De can distinguish two different ty!es of cell death, that differ one from another in many as!ects, !articularly #in mor!hologic changes #in !athogenesis - they have different causes - different meaning and significance /hese are#a!o!tosis #necrosis

4Y0ES OF CELL DEA4H 6 'ec%osis a'! a&o&tosis

A0O04OSIS #5istinctive ty!e of cell death# occurs in !hysiological and em ryological !rocesses and a!!ears to e a !henomenon where y tissues control cell !o!ulation num ers #a!o!tosis also occurs in !athological !rocesses, such as inflammation and cancer, in an attem!t y the ody to arrest cell !roliferation and tissue damage #7!o!tosis# recognized as s!ecial ty!e of cell death only recently 7!o!tosis# should e differentiated from common necrosis# differs oth in its iochemistry and in its mor!hology 1ts designation 2a!o!tosis3# it is a word from 4reek language, which originally refers to falling of leaves from trees in the autumn Ee*uence of events in a!o!tosis "# elevation of cellular calcium and ra!id reduction of volume of the cell $# activation of calcium#de!endent enzyme endonuclease which cleaves 5N7

%# fragmentation of 5N7 and marked condensation of oth nucleus and cyto!lasm 9# formation of a!o!totic odies# small a!o!totic odies are com!osed of fragments of nuclei with condensed chromatin, larger a!o!totic odies are com!osed of oth fragments of nuclei and condesed cyto!lasm with !reserved organelles ,# a!o!totic odies are ra!idly !hagocytosed y e!ithelial cells in nei ourghood or y macro!hages # cell dying y a!o!tosis are recognized and !hagocytosed soon after initiation of a!o!tosis ' role of vitronectin rece!tor# elongs to the family of so called integrins- adhesive cell surface and extracellular matrix !roteins with im!ortant functions in cell#cell and cell#matrix interactions( &or!hologic changes in a!o!tosis ra!id volume reduction and formation of cyto!lasmic le s # 2shrinkage necrosis3 loss of cell # cell contacts formation of a!o!totic odies !hagocytosis of a!o!totic odies y macro!hages, within which they undergo hydrolytic !hagocytic degradation Eignificance of a!o!tosis - !rogrammed cell death, cell suicide, since it a!!ears as a!!arently active !rocess# it re*uires energy and !rotein synthesis. 7!o!tosis is de!endent on gene activation and new !rotein synthesis. 1t is thought that the !rocess is regulated y a num er of a!o!tosis#associated genes. /hese include cl#$ !rotein, which inhi its a!o!tosis and therefore extends cell survival, !#,% !rotein which normally stimulates a!o!tosis ut mutated or a sent favors cell survival. #it re*uires activation of enzyme a!o!tosis seems to e res!onsi le for cell destruction in numerous !hysiologic events #a!o!tosis leads to removing of unwanted cells &h"sio$o-ica$ a&o&tosis: occurs in a num er of situations #is involved in normal tissue turnover #in hormone#induced atro!hy 'endometrium in menstrual cycle, mammary gland in meno!ause( # in develo!ing tissues, #!rogrammed cell destruction in em ryogenesis, for exam!le formation of digits &atho$o-ica$ a&o&tosis: a!o!tosis may e involved in res!onse to !athologic stimuli,

10

#such as viral infection 'for exam!le# Councilman odies in liver cells in viral he!atitis( #tumor regression induced y chemothera!y #!ro a ly the most interesting as!ect is s!ontaneous occurrence of a!o!tosis in solid tumors of various ty!es which is now eing studied very intensively # involvement of a!o!tosis in tumor growth

NECROSIS is the most common !attern of cell death

in contrast to a!o!tosis# necrosis may e defined as the mor!hologic changes that following the cell death in a living tissue or organ resulting from the !rogressive degradative activity of catalytic enzymes /hese enzymes are derived either from dying cells themselvesa)to$"sis or from lysosomal enzymes of leukocytes, referrred to as - hete%o$"sis #7!o!tosis is a death of isolated cellFcells and ty!ically is not associated with tissue reaction, in contrast mor!hologic changes of necrosis are ty!ically caused y tissue reactivity, such as active increase in lood su!!ly of the tissue surrounding necrosis, #infiltration of the vicinity of necrotic area y inflammatory cells, es!ecially y leukocytes #circumscri!tion of the necrotic focus and su se*uent healing

Nec%osis is the sum of the mor!hologic changes that follow cell death in living tissue or organ. /hese changes result from !rogressive degradative activity of enzymes of lethally injured cells 'autolysis and heterolysis( on one hand side# and denaturation of structural !roteins two !rinci!al !rocesses influence the changes of necrosis : "#enzymatic digestion of the cell $#denaturation of !roteins DEAD CELL MOR0HOLO/Y: c"to&$asm# increased eosino!hilia#attri uta le in !art to the loss of normal cyto!lasmic aso!hilia caused y the 0N7 and in !art y increased inding of eosin to denatured intracyto!lasmic !roteins more glassy a!!earance of the cell cyto!lasm#due mainly to the loss of glycogen !articles
-

11

')c$e)s6 nuclear changes can e reversi le #clum!ing of the chromatin with large aggregates attached to the nuclear mem rane or irreversi le# 5.6 &"8'osis 9 nucleus !rogressively shrinks and ecomes dense mass of tightly !acked chromatin 2.6 8a%"o$"sis - !rogressive dissolution of nuclear chromatin due to action of 5N7ases of lysosomal origin 3.6 8a%"o%%he,is - nucleus may reak u! to many clum!s Causes of necrosis: 1dentical as those of cell injury in general terms, such as mechanical, chemical, !hysical, infectious agents, and hy!oxiaFanoxia
-

MOR0HOLO/ICAL 4Y0ES OF NECROSIS ".# C.74UC7/1V@ N@C0.E1E #most common !attern of necrosis, is characteristic of hy!oxic cell death macrosco!ic a!!earance: firm consistency, yellowish colour, dry a!!earance of the cut section #this !attern of necrosis#most commonly results from sudden severe ischemia 'is encountered mostly in solid organs, such as kidney, heart, s!leen, adrenal gland( !athogenesis: Coagulative necrosis im!lies !reservation of the asic outline of coagulated cells for several days # nucleus usually disa!!ears, ut the sha!e of cell is !reserved #8resuma ly, the !attern of coagulative necrosis results from severe intracellular acidosis which denaturates not only of structural !roteins, ut also enzymes 'this lock ra!id !roteolysis of the cell( finally, the necrotic cell reaks into fragments that are removed y !hagocytosis of the cellular de ris ' y !roteolytic enzymes of leukocytes and macro!hages, immigrating into the necrotic focus( /he est exam!le of coagulative necrosis# m"oca%!ia$ i'.a%ctio' gross a!!earance of acute myocardial infarct changes with time fewer than G#"+ hours# ischemic area is slightly !aler, hardly discerna le even early infarct can e visualized y various histochemic reactions that may show de!letion of oxidative enzymes from infarcted area microsco!ic a!!earance # in early acute infarction# cell swelling !yknosis, eosino!hilia of cyto!lasm y "G#$9 hours #the infarct ecomes a!!arent grossly # !ale, more shar!ly circumscri ed, hy!eremic order#

12

microsco!ically: total necrosis with loss of nuclei, heavy infiltrate of leukocytes, macro!hages y %#H days #more a!!arent hy!eremia at the order of infarct, yellow# rown color, soft consistency end of "st week # infarct ecomes circumscri ed y highly vascularized scar tissue microsco!ically: there is a !rominent fi rovascular reaction in margins :th week # total re!lacement y scar - m"o.i+%osis

$. C1IU@67C/1V@ N@C0.E1E #results from the ra!id action of hydrolytic enzymes and occurs always when autolysis and heterolysis !revail over denaturation of !roteins #characteristic of ischemic 'ec%osis o. +%ai', &a'c%eas also common in acterial lesions # due to activity of enzymes of acterial and leukocytic origin good exam!le of li*uefactive necrosis is +%ai' i'.a%ctio' gross mor!hology# necrotic area ecomes very soft and fluidy# these changes are first detecta le at a out "$ hours within $#% day softening and discoloration ecome more a!!arent in large infarcts# there is marked swelling, tissue li*uefaction results in su se*uent !seudocystic degeneration no fi rous scar is formed, necrotic area changes into &ostma$atic &se)!oc"st '!ostnecrotic !seudocyst( -cystic s!ace filled with de ris, fluid

%. 67/ N@C0.E1E #this refers to necrosis in adi!ose tissue #due to action of activated li!ases most common#in ac)te &a'c%eatic 'ec%osis, in which active !ancreatic enzymes cause focal necrosis of the !ancreas and the adi!ose tissue throughout the a domen #li!ases are activated and released and destroy not only !ancreatic tissue itself ut also fat cells in the !ancreas and also fat cells throughout the !eritoneal cavity # Ba$se% 'ec%osis- shar!ly circumscri ed foci of enzymatic necroses of fat tissue with shadowy outlines surrounded y a zone of inflammation the released fatty acids then com!lex with calcium to create calcium soa!s

13

to the naked eye the necrotic foci a!!ear o!a*ue and chalky white or yellowish

9. C7E@.UE N@C0.E1E #another distinctive ty!e of necrosis that is a com ination of coagulative and li*uefactive necrosis. 1t is encountered in tu erculousis. 4ross mor!hology: caseous necrosis a!!ears grossly as soft, fria le, whitish#gray de ris resem ling cheesy materialAhence the term 2caseous necrosis3. /his a!!earance has een attri uted to the s!ecific li!o!olysaccharides of the ca!sule of the agent, tu erculous acillus ' &yco acterium tu erculosis(# the exact interactions with dead cells are not com!letely understood. &icrosco!y: <istologically, caseous necrosis a!!ears as amor!hous eosino!hilic material with cell de ris /he caseous necrosis is surrounded y s!ecific granulomatous inflammatory reaction 'e!ithelioid histiocytes, giant cells of Canghans ty!e, lymfocytes, !lasmacytes(.

,. 61B01N.15 N@C0.E1E #is a ty!e of connective tissue necrosis seen !articularly in autoimmune disease collagen and smooth muscle are affected 'for exam!le# in !olyarteriitis nodosa# fi rinoid necrosis affects lood vessel walls( #fi rinoid necrosis is characterized y loss of normal structure of collagen fi res #causing teh change of tinctorial features of collagen# right eosino!hilia which resem les fi rin# derived from !lasmatic fi rinogen

/AN/RENOUS NECROSIS #it is not a distinctive ty!e of necrosis, it is a necrosis secondary modified usually y the attack of acterial agents. /he term gangrene is commonly used in clinical !ractise to descri e a condition when extensive tissue necrosis is com!licated y acterial infection. /here are three major ty!es of gangrene: dry gangrene wet gangrene gas gangrene #dry gangrene# necrotic tissue a!!ears lack and dry and is shar!ly demarcated from via le tissue

14

most commonly it occurs in extremities as a result of ischemic coagulative necrosis doe to arterial o struction Dhen the coagulative !attern !revails # !%" -a'-%e'e develo!s when li*uefaction is more !ronounced# 7et -a'-%e'e develo!s #wet gangrene# results from severe acterial inection of necrotic area most commonly it occurs in the extremities due to arterial o struction, ut also in the internal organs, such as intestine# most common exam!le# in acute su!!urative a!!endicitis grossly# tissue is swollen, reddish# lack with extensive li*uefaction wet gangrene is severe com!lication associated with high mortality rate #gas ganrene# is a wound infection caused y Clostridium !erfringens and other ty!es of Clostridia #it is characterized y extensive necrosis and tissue destruction and !roduction of gas y fermentative action of acteria grossly# a!!earance similar as in wet gangrene with additional !resence of gas in tissues c%e&it)s6 a sound that can e detected y !al!ation of necrotic tissues gas gangrene is associated with a high mortality rate NECROSIS a'! A0O04OSIS

15

N@C0.E1E Etimuli <istology hy!oxia, toxins

78.8/.E1E !hysiologic and !athologic

cellular swelling, coagulation single cells,chromatin necrosis, disru!tion condensation, of organelles a!o!totic odies random, diffuse internucleosomal

5N7

reakdo wn

&echanisms

7/8 de!letion, mem rane injury, free radical damage

gene activation, endonuclease

/issue reaction inflammation

no inflammation, !hagocytosis of a!o!totic odies

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