PATHOLOGYI

NTRODUCTI
ON

 Thewor d"pathology"isfr
om AncientGreek:pathos-"f
eel
ing,
suff
ering"and
–logos-"thestudyof "
.
 Thest udyofdisease;iti
sdevotedtothestudyoft hebi
ochemical
,structur
al,
andf unct
ionalchangesincell
s,ti
ssues,andor gans.
 Servesast hebri
dgebet weenthebasicsciencesandclini
calmedi
cine, andis
thescienti
ficf
oundat i
onforal
lofmedi ci
ne.

 Generalpathol
ogy :concer
nedwi t
hther eacti
onsofcell
sandtissuest
o
abnormalstimul
i andtoinheri
teddefect
s.
 Systemicpathol
ogy :examinesthealter
ationsinspeci
ali
zedt
issuesand
organsthatareresponsibl
efordisor
derst hati
nvolv
etheseor
gans.

Pat
hologyaddr esses4componentsofdisease:
 cause/et i
ology/
 mechani smsofdev el
opment/pathogenesi
s/
 str
ucturalalter
ati
onsofcel
l
s/ morphologi
cchanges/
 theconsequencesofchanges/ cl
i
nicalmanifest
ati
ons/

 Health: compl etephysi

cal,mental
andsoci alwell
bei ng,
notmer el
yabsenceof
disease…
 Disease: expressi
onofdiscomfort
 I
llness:t her eacti
onoftheindi
vi
dualtodiseaseinthef orm ofsympt oms
(compl aint softhepati
ent)andphysi
calsigns(eli
citedbytheclini
cian).
 Thoughdi seaseandill
nessarenotseparable,t
hest udyofdiseasesi sdonein
pathologywhi l
ethel
earningandmanagementofi l
lnessesisdoneincl ini
cs.

 Patientistheper sonaf f
ectedbydi sease.
 Lesionsar ethechar acter
isti
cchangesi ntissuesandcel l
spr oducedby
di
seasei nani ndivi
dual orexper iment alanimal.
 Pathologicchangesormor phologyconsi stofexami nat
ionofdi seasedtissues.
 Pathologicchangescanber ecogni sedwitht henakedey e(grossor
macr oscopicchanges)orst udiedbymi croscopicexami nati
onoft issues.
 Causal factorsresponsi blefort hel esi
onsar eincludedi neti
ol ogyofdisease
(i
.e.‘why’ofdi sease) .
 Mechani sm bywhi cht helesionsar eproducedi ster medpat hogenesisof
di
sease( i
.e.‘how’ofdi sease).
 Funct i
onal i
mpl i
cationsoft hel esionf el
tbyt hepat ientaresy mptoms
 andt hosedi scoveredbyt heclinicianaret hephy sicalsigns.
Methodsi
nthegener alandcl i
nicalpathol
ogy
 Autopsy
– hospi tal(pathologo-anathomic)
 per formedbypat hologi
stsi
nhospi
tali
zedpati
entswhodiedof
nat uralcauses
– forensi c
 i nvest i
gatethedeat hi
ncasesofvi
olenceorpresumedv
iolence
 Biopsy
– histological
– cytological
AUTOPSY

 t het erm" aut opsy "der ivesf rom t heanci entGr eek" aut opsi a":"toseef or
onesel f ",
"autos“-" onesel "and"opsi
f s“-" eye“ .
 ahi ghl yspeci alizedsur gi cal procedur et hatconsi stsofat hor ough
exami nat ionofacor pset odet er mi net hecauseandmannerofdeat handt o
evaluat eanydi seaseori nj ur yt hatmaybepr esent .
 Ai ms:
 t oi dent ifyt hecauseofdeat h
 t ocl arifycaseswi t houtcl inical di agnosisori nt hosei nwhicht he
pat ientdeat hwasunexpect ed
 r ecogni tionoft heef fectoft het reatmenti nt heev oluti
onoft hedi sease
 r ecogni tionofnewdi seasesandofnewl esi onpat terns
 sour ceofi nfor mat ion, allowi ngt hemaki ngofpr ecisest ati
sti
csont he
mostf requentdi seases
 mat erial fort her esi dent s,student sandst af flear ning
 mat erial forsci ent ificr esear ch.
BI
OPSY
 ist hemedi cal remov aloft issuef r
om al ivi
ngsubj ecttodet erminethe
presenceorext entofadi sease
 commonl yper for medbyasur geoni nv olvingsampl i
ngofcel l
sort i
ssuesf or
exami nat ion
 isgener allyexami nedunderami croscopebyapat hologi st
Anexcisi
onalbi opsy
 anent irel umporsuspi ciousar eai sr emov ed.
 Whent hespeci meni sev aluat ed, i
naddi ti
ont odi agnosi s,theamountof
uninv olv edt i
ssuear oundt hel esi on, thesur gi
calmar ginoft hespecimeni s
exami nedt oseei ft hedi seasehasspr eadbey ondt hear eabi opsi
ed.
Aninci
sionalbi opsyorcor ebi opsy
 whenonl yasampl eoft issuei sr emov edwi thpr eser vat i
onoft hehistological
architect ur eoft het i
ssue’ scel l
s

Oncet hetissueisremov edfrom thepat i

ent
,ithastobei mmediatelyfi
xedbyputti
ng
i
tintoadequat eamountof10%f ormalinbef
or esendingi
ttothepat hologi
st.
Thepur poseoffixati
onis:
1.topr ev
entaut ol
ysi
sandbact eri
aldecomposi t
ion;
2.tocoagul atetheti
ssuetopr eventlossofeasilydif
fusi
blesubstances;
3.toleavet heti
ssuesinacondi t
ionwhichfacili
tat
esdiff
erent
ialstaini
ngwithdy
es
andot herreagents.
  Oncet het i
ssuear r
ivesatt hepat hologydepar t
ment , t
hepat hologistwill
exam
i
tmacr oscopically–naked- ey eexami nationoft i
ssues.
 Pr opergr osstissuecut t
ing, grossdescr i
pt i
onandsel ectionofr epresent
ativ
e
tissuesampl ei nlargerspeci mensi sacr ucial partoft hepat hol ogi
c
exami nat i
onoft i
ssuesubmi tted.
 Thent het i
ssuei spr ocessedt omakei tr
eadyf ormi croscopi cexami nati
on.
Thewhol epurposeoft het issuepr ocessi ngi stopr epar eav er ythi
nt i
ssue(i.
e.
fivet osev enμm oronecel l thicktissue)whi chcanbecl ear l
yseenundert he
mi croscope.
 Thet issuei spr ocessedbyput t i
ngi tintodi fferentchemi cals.
 Itist heni mpr egnat ed(embedded)i npar affin,sectioned( cut)intothinsli
ces,
&i sf inallystained.Thest ainscanbeHemat oxy l
in/
Eosi nst ainorspeci al
st ainssuchasVanGi eson, PAS, I
mmunohi st ochemi stry,etc..
.
 TheH&Est ai
ni srout i
nelyused.I tgiv esthenucl eusabl uecol or&t he
cy toplasm &t heext racellul
armat r
ixapi nkishcol or.
 Thent hepat hologistwi l
llookf orabnor mal structuresi nthet issueandbased
ont hisabnor mal mor phologyhe/ shewi l
l maket hedi agnosi s.
 Hi stopat hologyi susual l
yt hegol dst andar df orpat hologi cdiagnosi s.

HI
STOCHEMI STRY
 Incer tain‘special’
cir
cumst anceswhent hepat hologi stwant stodemonst rat
e
cert ainspecifi
csubst ancesorconst i
tuentsoft hecel lstoconf i
rm eti
ologi
c,
histogeni corpat hogeneticcomponent s,specialstains( al
sot ermed
histochemi calstai
ns),areempl oyed.
 Someoft hesubst ancesf orwhichspecialstainsar ecommonl yusedina
sur gicalpathologylaboratoryareamy loi
d,carbohydr ates,lipi
ds,protei
ns,
nucl eicacids,connect i
vetissue,micr
oorganisms, neur alt
issues,pigments,
mi ner al
s.

Cr
yost
at/frozensect i
on
 Cryostatorf rozensectioneliminatesallthest epsoft issueprocessingand
paraff
in-embeddi ng.Instead,thetissueisqui cklyfrozent oiceatabout–25° C
whichact sasembeddi ngmedi um andt hensect ioned.Sect i
onsaret hen
readyforst aini
ng.
 Frozensect i
onisar api
di ntr
aoper at
ivediagnost i
cpr ocedur efort
issues
beforepr oceedingtoamaj orradicalsurgery.
 Besides,itisalsousedf ordemonst rat
ionofcer tainconst it
uentswhichar e
normallyl ostinprocessinginalcohol orxylenee. g.fat,enzymeset c.

I
MMUNOHI STOCHEMI STRY
 Immunohi stochemi str
y(IHC)isat echniqueusedi nhistopathology
l
aboratori
est ol ocaliseanti
gensi nt i
ssuesect ionsusingspeci f
icant i
bodies.
 Theantigensofi nterestareusual lysubst ancesf oundonpar ti
cularcelltypes.
Commer cially-
pr oducedant i
bodi esagai nstthesubst anceofi nterestbindto
anti
gensint het issuesect i
on.
 Theantibody -
ant igencompl excanbev i
sualisedinsev eralways,themost
commonbei ngacol ourchanget hatcanbeseenundert hemicroscope.
 IHCisusedt oident if
yandchar act erisethedi str
ibuti
onofant i
gensi nawi de
rangeoftissuet y pes.Manycancer s,forexampl e,expresscertainantibodies
accordi
ngt ot heirtissueoforigin.
  I HCcant hereforebeusedt odi f
ferent i
atebet weencancert hathasar i
senin
thebreastorbowel .Thi si sextremel yusef ulindet erminingt r
eat mentoptions
asdifferentcancer sr espondt odifferenttreat ment s.
Condi
ti
onsi dent i
fi
edwi thbi opsi es
 pat hologicexami nationofabi opsycandet erminewhet heral esionisbenign
ormal ignant,andcanhel pdifferentiatebet weendi fferenttypesofcancer .
 Exami nationoft hef ullspeci menwoul dconf irmt heexactnat ureofthecancer
/subclassifi
cationoft umourandhi st ologic"gradi ng"/andr ev ealtheextentof
i
t sspread/ pathologi c" staging"/
 I nfl
ammat orycondi tions: abiopsyoft hetempor al arteri
esisof tenperformed
forsuspect edv ascul i
tis.
 I ninfl
ammat orybowel di seasef r
equentbi opsiesar etakent oassesst he
activ
ityofdi seaseandt oassesschangest hatpr ecedemal ignancy .
 I nhepat i
tis,mostbi opsi esar enotusedf ordi agnosi s, whichcanbemadeby
othermeans.Rat her,itisusedt odet erminer esponset otherapywhi chcanbe
assessedbyr educt ionofi nfl
ammat i
onandpr ogressi onofdi seasebyt he
degreeoff i
brosis.

CYTOPATHOLOGY
 t hest udyofcel lsfrom v ari
ousbodysi test odeter minet hecauseornat ureof
di sease.
 Compar edt ohi stopat hologict echni quei tischeap, t
akesl esstimeandneeds
noanest hesi at ot akespeci mens.
 Ther earedi fferentcy topathologi cmet hodsincludi ng:
1.Exf ol i
at ivecy tol ogy
Ref er st ot heexami nat i
onofcel lsthatar eshedspont aneousl yintobodyf lui
ds
orsecr etions.
Exampl esi ncl udesput um, cer ebrospi nal flui
d,urine, effusionsinbodycav iti
es
(pleura, per icardium, peritoneum) ,nippl edi schar geandv agi nal di
scharge.
2.Abr asi v ecy tology
Ref er st omet hodsbywhi chcel l
sar edi sl
odgedbyv ar i
oust oolsfrom body
sur f
aces( skin, mucousmembr anes, andser ousmembr anes) .
E. g.pr epar at i
onofcer vi
cal smear swi thaspat ulaorasmal lbrushtodet ect
canceroft heut erinecer v i
xatear lyst ages.Suchcer vical smear s,al
socal l
edPap
smear s, cansi gnificant lyreducet hemor talit
yf r
om cer vi
cal cancer .
3.Fine- needl easpi rat i
oncy tology(FNAC)
InFNAC, cel lsar eobt ainedbyaspi ratingt hediseasedor ganusi ngav erythin
needl eundernegat ivepr essur e.Virtual l
yanyor ganort i
ssuecanbesampl edbyf i
ne-
needl easpi r
ation.
Super fi
cial organs( e. g.thyroid, breast ,lymphnodes, skinandsof tti
ssues)can
beeasi lyaspi r
at ed.Deepor gans, suchast hel ung,medi ast i
num, li
ver,pancreas,
kidney ,adr enal gland, andr etroperit
oneum ar easpi ratedwi thgui dancebyul tr
asound
orCTscan.

Themai nappl icati

onsofcy t
ologyincl
udethefol
lowing:
1.Scr eeningf ortheearl
ydetecti
onofasympt omati
ccancer
Forexampl e,theexaminati
onofscrapi
ngsfrom cerv
ixforear
lydet
ecti
onand
preventi
onofcer v
icalcancer
.
2.Diagnosisofsy mptomat i
ccancer
Cytopathologymaybeusedal oneori
nconjuncti
onwithothermodali
ti
est
o
diagnoset umour sr eveal edbyphy sical orr adi ological exami nations.I tcanbeusedi n
thediagnosi sofcy sts, inflammat orycondi tionsandi nf ectionsofv ariousor gans.
3.Sur v ei l
lanceofpat ient streat edf orcancer
Forsomet ypesofcancer s,cy tologyi sthemostf easi blemet hodof
surveill
ancet odet ectr ecur rence.Thebestexampl ei sper i
odi cur inecy tologyt o
moni tort her ecur renceofcanceroft heur inar ytract .
Rev er
si blecel l
ul ari njur y
Pathogeni cf act or s:
Classificat i
on
1.Oxy gendepr ivat ion( hy poxi a,ischemi a)
2.Chemi cal agent sanddr ugs
3.Phy sical agent s
4.I nfectiousagent s
5.I mmunol ogi cr eact ions
6.Nut ri
tional imbal ances
7.Genet icder angement s
8.Agi ng
1.Hy poxi a
 =oroxy gendef iciency
– anext remel yimpor t
antandcommoncauseofcel linjur yanddeat h.
– shoul dbedi stingui shedf rom i schemi a( al ossofbl oodsuppl yina
tissueduet oimpededar teri
al fl
oworr educedv enousdr ainage) .
 Reasonsf oroxy gendepr i
vation
– I schemi a
– i nadequat eoxy genat i
onoft hebl ood( pneumoni a)
– r educt ioni ntheoxy gen- carry ingcapaci tyoft hebl ood( anemi a)
2.Chemi calAgent s
 Anenor mousnumberofchemi cal subst ancescani nj urecel ls
– Concent r
at edgl ucoseorsal t
– Oxy genatsuf ficientlyhi ghpar ti
al pressur es
– Poi sonsandpot ent i
allyt oxicagent s( airpol l
utant s,et hanol )
– Ther apeut icdr ugs
 i fusedexcessi v elyori nappr opr iately
3.Phy si calAgent s
– Tr auma, ext remesoft emper at ures, radi ation, electricshock, sudden
changesi nat mospher icpr essur e
4.Infect iousAgent s
– Vi ruses, ricket t
si aes, bact eria, fungi,pr ot ozoas, tapewor ms
5.Immunol ogi cReact ions
– aut oimmuner eact i
onsagai nstone' sownt issues
– al lergi cr eact ionsagai nstenv ironment al subst ancesi ngenet i
cally
suscept iblei ndi viduals
6.Nut ritionalI mbal ances
– Nut ri
tional def i
ci encies-pr ot ein-calor i
ei nsuff i
ciency ,speci f
icv it
amin
def icienci es
– Excessesofnut riti
on
obesi ty–DM
di et sr i
chi nani mal f
at-at her oscl erosis
7.Genet icDef ect s
– congeni tal mal for mat ionsassoci atedwi thDownsy ndr ome, sickl
ecell
 anemi a
– defi
ciencyoff
unct
ional
prot
eins-
enzy
mesi
ninbor
ner
ror
sof
metabolism
8.Agi
ng
– al
terat
ionsi
nrepl
i
cat
iveandr
epai
rabi
l
iti
esofi
ndi
vi
dual
cel
l
sand
ti
ssues

Cel
linj
ury
 isdef i
nedasav ar
iet
yofstressesacellencount
ersasar
esultofchangesi
n
i
tsinternalandexter
nalenvir
onment.
 Thecel l
ularr
esponsetostressmayvaryanddependsuponthefoll
owing
vari
ables:
i
)Thet ypeofcellandti
ssuei nv
olv
ed.
i
i)Extentandtypeofcelli
njury.

Whent hereisincreasedf unctionaldemand, thecellmayadaptt ot hechangeswhi ch

areexpr essedmor phologicall
yandt henrevertbacktonor mal af
terthest r
essis
remov ed
(cell
ularadaptations) .
Whent hestressismi l
dt omoder ate,theinj
uredcellmayr ecover(reversiblecell
i
njury),whilewhent heinjuryispersist
entcelldeathmayoccur( i
rr
ev ersiblecell
i
njury).
Ther esidualeffectsofr eversi
blecellinj
urymayper sistinthecellasev i
denceofcel l
i
njuryatsubcel lul
arl evel(subcell
ularchanges),ormet abol
itesmayaccumul ate
withi
nt hecell(intr
acel l
ularaccumul ati
ons).

Pat
hogenesi sofcel li njury
 Per sistentorsev er ehy poxi aandi schemi aul t
imat elyleadt of ail
ureofATP
generat i
onanddepl etionofATPi ncel l
s.
 Reducedact ivityofpl asmamembr aneATP- dependentsodi um pumps,
result
ingi ni ntracel l
ul araccumul ationofsodi um andef fl
uxofpot assium.The
netgai nofsol ut eisaccompani edbyi soosmot i
cgai nofwat er ,causingcel l
swellinganddi lationoft heER.
 Pr olongedorwor seni ngdepl etonofATPcausesst
i r
uctur aldi sruptionoft he
proteinsy nt heticappar atus,mani festedasdet achmentofr ibosomesf rom the
roughER( RER)anddi ssoci at
ionofpol ysomesi ntomonosomes, witha
consequentr educt i
oni npr oteinsy nthesis.
 Thecompensat or yincr easeinanaer obicglycolysisleadst ol act i
caci d
accumul ation, decr easedi ntr
acellularpH, anddecr easedact ivityofmany
cell
ularenzy mes.
 I nischaemi a, aerobi cr espirati
onaswel lasglucoseav ailabilityar ebot h
compr omi sedr esultingi nmor esev ereandf asteref fectsofcel li
njury.
Ischaemi ccel linjuryal socausesaccumul ati
onofmet abol i
cwast epr oduct s
i
nt hecel ls.
 Ont heot herhand, nhy
i poxiafrom ot hercauses( RBCdi sor der s,hear tdisease,
l
ungdi sease) , anaer obi cglycolyticATPgener ationcont inues, andt huscel l
i
njuryi slesssev ere.
 Howev er,highl yspeci alisedcellssuchasmy ocardium, pr oximal tubularcells
oftheki dney ,andneur onsoft heCNSar edependentsol elyonaer obic
 r
espi r
ati
onforATPgener ati
onandt husthesetissuessuff
erfr
om il
l-ef
fect
sof
i
schaemi amoresev erel
yandr api
dly
.
 t
hest ageofcell
inj
ur yatwhichthederangedfunct i
onandmor phol
ogyofthe
i
njuredcell
scanreturntonor mali
fthedamagi ngst i
mulusisr
emov ed.
 i
nt hepast
– Degenerati
on( degenerare–changing)
– Dy st
rophi
a(dy s+tr
ophe–abnor malfeeding)

 Thet womai nmor phologiccorr

elatesofreversibl
ecellinjur
yarecel
lul
ar
swellingandabnor malintr
acell
ularaccumul at
ions.
I
nr eversi
blei nj
ury,
cell
sandint r
acell
ularorganell
estypical
lybecomeswol l
en
becauset heyt akeinwaterasar esul
toft hefail
ureofenergy -
dependenti
onpumps
i
nt heplasmamembr ane,l
eadingtoani nabil
itytomai nt
ainionicandfl
uid
homeost asis.

Cel
lul
ar(cloudy )swel li
ng
 Gr oss: itcausespal lor(asaresultofcompressi
onofcapi l
l
aries),
increased
tur
gor ,andani ncreaseinorganwei ght
.
 Mi croscopi cexami nati
onmayshowsmal l,
clearvacuoleswi thi
nthe
cytoplasm; theser epresentdist
endedandpinched-offsegment softhe
endopl asmi cr eti
culum (ER).Thenucleusmayappearpal e.
 Thi spat ternofnonl ethali
njuryi
ssomet i
mescalledhy dropicchangeor
vacuolardegener ati
on.
Abnor
mali ntracellularaccumul ati
ons
 Undersomeci rcumst ancescell
smayaccumul ateabnor mal amount sof
vari
oussubst ances
– Li pi
ds
– Pr oteins
– Gl ycogen
– Pi gment s

 Theymaybehar mlessorassoci
atedwithvary
ingdegreesofinj
ury
 Maybelocatedinthecyt
oplasm,withi
norganell
es(l
ysosomes),orinthe
nucl
eus
 I
tmaybesy nthesi
zedbytheaffect
edcellsormaybepr oducedelsewhere

3mai
npat hway sofi ntracell
ul araccumul ations
 Anor mal subst ancei spr oducedatanor mal orani ncr
easedrate,butt he
met aboli
cr at
ei si nadequat etor emov eit(fattychangei ntheli
ver).
 Anor mal oranabnor mal endogenoussubst anceaccumul atesbecauseof
geneticoracqui r
eddef ectsinitsfolding,packagi ng,tr
ansport,
orsecr eti
on
(defectinanenzy mer esultstof ai
l
ur etodegr adeamet aboli
te–st orage
diseases)
 Anabnor mal exogenoussubst anceisdeposi tedandaccumul atesbecause
thecellshav enoenzy mat i
cmachi ner ytodegr adet hesubstancenort he
abil
itytotranspor tittoot hersites(Accumul ationsofcarbonpar t
icl
es) .

I
ntr
acel
lul
araccumul
ati
ons
 Lipi
ds
– Neutral
Fat
 – Chol ester
ol
 Pr
otei
ns
– “ Hyali
ne”=any“
prot
einaceous”pi
nk“
glassy
”subst
ance
 Gl
ycogen
 Pi
gment s
– Endogenous
– Exogenous

I
ntr
acel
lularl
ipi
daccumul ati
ons
 Sitesoflocal
izati
on
– withi
nt heparenchy malcell
s–inlipidsmetabol
ism abnor
mal
i
ties
 =degener at
ioadiposa
– wi t
hinthefatcel l
sofconnectivetissue(
adipocyt
es)
 Gener alobesi t
as
 Local obesi t
as-lipomatosi
s
– withi
nt hemacr ophages–i nli
pidphagocytosi
s
 =f oam cel l
s

FATTYCHANGE( STEATOSI S)
 Fat tychange, steatosi
sorf att
ymet amor phosisist
heintr
acell
ular
accumul ati
onofneut r
alfatwithi
npar enchymal cel
l
s.
 Thedeposi tisint hecytosolandr epr
esentsanabsol ut
eincreaseint
he
i
ntracell
ularli
pids.
 I ti
sespeci al
lycommoni ntheliv
erbutmayoccuri nothernon-fat
tyt
issues
l
ikethehear t,skeletal
muscl e,ki
dneysandot heror
gans.

FattyLiver
ETIOLOGY.Fat t
ychangei nt heli
v ermayr esul tfr
om oneoft het wot y
pesofcauses:
1.Condi t
ionswi thexcessf at(hyper l
ipidamei a),
exceedingt hecapacit
yofthe
l
ivertomet abol isei t.
 i )Obesi ty
 i i
)Diabet esmel li
tus
 i i
i)Congeni tal hyper l
ipidaemi a
2.Livercelldamage, whenf atcannotbemet abol i
sedinit.
 i )Alcohol icliverdi sease( mostcommon)
 i i
)St arvation( decr easedsy nthesisof‘ l
ipidacceptorprotein’)
 i i
i)Chr onici l
lnesses( e.g.tuber cul
osi s)
 i v)Hy poxia( e. g.anaemi a,cardiacf ailure)
 v )Hepat otoxi ns( e.g.carbont et r
achl oride,chlor
oform,ether,afl
atoxi
nsand
otherpoi sons)
 v i)Dr ug-i
nducedl ivercellinjury(e.g.admi nist
rati
onofmet hot
rexate,
ster
oids,
CCl4, halot haneanaest hetic,t
et r
acy clineetc)
 v ii
)Rey e’
ssy ndr ome

Grossly,
thel
iverinfat
tychangeisenl
argedwit
hat ense,
glist
eni
ngcapsuleand
r
oundedmar gins.Thecutsurfacebul
gessli
ght
lyandispale-y
ell
owtoyell
owand
i
sgr easytot
ouch.

Micr
oscopicall
y,char
acteri
sti
cfeat
urei
sthepr
esenceofnumer
ousl
i
pidv
acuol
es
i
nthecytoplasm ofhepatocyt
es.
  FatinH&Est ai
nedsecti
onpreparedbyparaf
fi
nembeddi ngtechniqueappear
non-staini
ngvaul
oesbecauseiti
sdissol
vedinalcohol
.
 Fatcanbedemonst rat
edinfreshunfi
xedti
ssuebyf r
ozensecti
onf oll
owedby
fatstainssuchasSudandyes(SudanIII
,I
V,Sudanblack)andoilredO.

Li
pidaccumul
ati
onswi thinthefatcell
s
 =Obesitas
 Generalobesi
tas
– wit
hint
hef atcellsofadiposetissue
 Lipomatosis(
local obesi
tas)
– wit
hint
hef atcellsofconnectiveti
ssueofdiffer
entor
gans
 Hear t–subepicardium ofrightchamber
 Pancr eas–i nt
erl
obularconnect i
veti
ssue

Li
pidaccumul ati
onswi thi
nt hemacr ophages-Li pidphagocy t
osi s
 Phagocy ti
ccellsmaybecomeov erl
oadedwi t
hl i
pid(tri
glyceri
des, cholester
ol,
andchol est
erolesters)insev eraldi
ffer
entpat hologicprocesses.
I
nnecrosis:i
ncont actwiththelipiddebr i
sofnecr oticcell
st heyst uffedwith
phagocyt
osedl i
pid=foam cel l
s
 Inatheroscler
osis-smoot hmuscl ecellsandmacr ophagesar efi
ll
edwi thli
pid
vacuolescomposedofchol esterolandchol esterylester
s
 t hesegiv eatheroscler
oticplaquest heirchar acteri
sti
cy ell
ow
colorandcont ri
but etothepat hogenesi soft helesion

I
NTRACELLULARACCUMULATI ONOFPROTEI NS
 Inpr ot
einuria,thereisexcessi verenaltubularr eabsor ptionofproteinsbyt he
proximal tubularepithelialcell
swhichshowpi nkhy al
inedr oplet
sint hei
r
cytoplasm.
 Thechangei sreversiblesot hatwithcontrol ofpr oteinuriatheproteindroplet
s
disappear.
 Thewor d‘hy al
ine’meansgl assy(hyal
os=gl ass) .
 Hy ali
neisadescr i
pt i
vehi stol
ogictermf orglassy , homogeneous, eosinophil
ic
appear anceofmat erialinhaemat oxyl
inandeosi n-stainedsect i
onsanddoes
notr ef
ertoanyspeci f i
csubst ance.
 Thecy toplasm ofact ivelyfunctioni
ngpl asmacel lsshowspi nkhy al
ine
inclusi
onscal edRussel
l l
’sbodiesrepresentingsy nthesisedi mmunogl obuli
ns.

I
NTRACELLULARACCUMULATI ONOFGLYCOGEN
 Indiabetesmel li
tus,thereisintracell
ularaccumul at
ionofglycogenindif
ferent
ti
ssuesbecausenor mal cel
lularuptakeofgl ucoseisimpaired.
 Glycogendeposi tsindi abetesmel li
tusar eseeninepithel
i
um ofdistalport
ion
ofproximal convolutedt ubuleanddescendi ngloopofHenle, i
nthe
hepatocytes,inbetacel lsofpancr eaticisl
ets,andincardi
acmuscl ecell
s.
 Depositsofgl ycogenpr oducecl earv acuolesinthecytopl
asm oftheaffected
cel
ls.

 Depositsofgl
ycogenproducecl
earvacuol
esinthecyt
opl
asm oft
heaffect
ed
cel
ls.
 Ingly
cogenstoragedi
seasesorgly
cogenosis,
ther
eisdef
ect
ivemetaboli
sm
ofglycogenduetogeneti
cdisor
ders.
Tesauri
smoses
LysosomalSt
orageDi
seases

 Ani nheritedl ackofal ysosomal enzy me, cat aboli

sm ofi tssubstrateremai ns
incompl eteandl eadi ngtoaccumul ationoft hepar tiallydegradedi nsoluble
met aboliteswi thint hel ysosomes
 Cl assifi
cat ion–ar ound60l ysosomal storagedi seases, eachresulti
ngf rom
thef unctional absenceofaspeci f
icl ysosomal enzy me
GaucherDisease
 Gaucherdi seaser esul tsf rom mut ationint hegenet hatencodes
glucocer ebr osidase, andt her esul tantdef i
ciencyoft hisenzy meleadst oan
accumul at ionofgl ucocer ebr osi dei nt hemononucl earphagocy ti
ccells.
 Nor mally,macr ophages, par ticul arlyint heliver,spl een, andbonemar r
ow,
sequent i
al lydegr adegl ycol i
pi dsder ivedfrom t hebr eakdownofsenescent
bloodcel ls.
 I nGaucherdi sease, thedegr adat ionst opsatt hel ev el ofglucocerebrosides,
whichaccumul at einmacr ophages.
 Thesecel ls—t heso- call
ed“ Gauchercel l
s”—becomeenl arged,becauseoft he
presenceofdi st endedl ysosomes, andt heyacqui r eapat hognomoni c
cytoplasmi cappear ancechar act erizedas“ wr i
nkledt issuepaper ”.
 Gauchercel l
sar ef oundi nt hel i
v er, spleen,lymphnodes, andbonemar row.
 Onev ari
ant ,type1, account sf or99%ofcasesofGaucherdi sease.Itis
character i
zedbycl inicalorr adi ogr aphi cbonei nvolv ementi n70%t o100%of
cases.
 Addi ti
onal feat urei shepat ospl enomegal y.Thespl eenof tenenlargesto
massi vepr opor tions, f
il
li
ngt heent ireabdomen.

PI
GMENTS
 Pigment
sar
ecolouredsubstancespr
esenti
nmostl i
vi
ngbeingsi
ncludi
ng
humans.
 Therear
e2broadcategor
iesofpigment
s:endogenousandexogenous

ENDOGENOUSPI GMENTS
 Endogenouspigment
sareei
thernormalconst
it
uent
sofcel
l
soraccumul
ate
underspecial
cir
cumst
ances
 Haemoglobinandnon-
haemoglobi
n-der
ivedpi
gments

Haemoglobi n-derivedPi gment s

 Haemosi der
ini si r
oncont ainingpi gmenti dent i
fi
ablebylightmi cr
oscopyas
golden- yell
owt obr own, granularpi gment ,especial
lywithinthemononuclear
phagocy tesoft hebonemar r
ow, spleenandl iverwherebr eak-downof
senescentr edcel l
stakespl ace.
 Excessi vest orageofhaemosi derinoccur sinsituati
onswhent herei
s
i
ncr easedbr eak- downofr edcel l
s.
Haemosider i
n
 Br owni ndurat i
oni nthel ungsasar esultofsmal lhaemor rhagesasoccurin
mitral stenosi sandl eftventri
cul arf ai
lure.
 Mi cr oscopyr eveal st
hepr esenceof‘ heartfai
lurecell
s’whi chare
haemosi derin-ladenalv eolarmacr ophages.
BI
LIRUBIN
 Bi l
ir
ubinisthenor mal non-i
roncont ainingpigmentpresentinthebi l
e.
 Excessofbi lirubi
norhy per-
bil
ir
ubinaemi acausesani mportantcl
inical
condit
ioncalledjaundice.
 Excessi v
eaccumul ati
onofbi l
ir
ubincanbeseeni ndiff
erentti
ssuesandf l
uids
ofthebody,especi al
lyinthehepat ocy t
es,Kupffercel
lsandbilesinusoids.
 Ski nandscler aebecomedi sti
nctlyy ell
ow.
 Jaundi cemayappeari noneoft hef ollowing3way s:
 Pr ehepati
corhaemol yti
c,whent herei sexcessivedestr
ucti
onofr edcells.
 Hepat ocell
ularthatresult
sf r
om failureofhepat ocyt
estomet abolisebil
irubin
andinabil
it
yofbi li
rubi
nt opassf r
om t hel i
vertoint
esti
ne.
 Post hepati
corobst r
ucti
ve,whichr esultsfrom obstr
ucti
ont otheout f
lowof
bi
lir
ubin.

Non-haemogl obin-deri
vedPi gment s
 Mel ani
nisthebr own-black,non-haemoglobin-
deriv
edpigmentnormally
presentinthehair,ski
n, choroi
doft heeye,meningesandadrenalmedulla.
 I tissynt
hesisedint hemel anocytesanddendrit
iccell
s,bothofwhichare
presentinthebasal cell
soft heepidermi
s.
Generalisedhyperpigment at
ion
 I nAddison’sdisease,thereisgenerali
sedhyperpigmentati
onoftheskin,
especial
lyinareasexposedt oli
ght,andofbuccal mucosa.

Focalhyper pigment ati

on
 Mel anot ictumour s, bothbenignsuchaspi gment ednaevi,andmal ignantsuch
asmel anoma, areassoci atedwi thincreasedmel anogenesis.
Generali
sedhy popi gment ati
on
 Al binism isanext remedegr eeofgener ali
sedhy popigmentat i
oninwhi ch
tyr
osi naseact i
vi
tyoft hemel anocy t
esisgenet icall
ydefectiveandnomel ani
n
i
sf ormed.
 Al binoshav eblondhai randsev er
ephot ophobi
a.Theyar ehi ghlysensiti
veto
sunlight.
Local
isedhy popigment ation
 Leucoder mai saf or m ofpartialalbi
nism andi sani nheri
teddi sor
der.
 Vi ti
li
goi slocal hypopi gment ationoft heskinandi smorecommon.I tmay
havef ami l
ialtendency .

Li
pof
usci n( WearandTearPi gment )
 Li pofuscinorlipochromei sy ellowish-browni nt
racellul
arlipi
dpigment( li
po=
fat,fuscus=br own).
 Thepi gmenti softenf oundi nat r
ophiedcel lsofoldageandhencet hename
‘
wearandt earpigment ’
.
 I tisseeni nt
hemy ocar dial fi
bres, hepatocytesandi nneur onsinseni
le
dement i
a.Howev er,thepi gmentmay ,
attimes, accumul aterapi
dlyi
ndi ffer
ent
cellsinwastingdiseasesunr elatedt oaging.
 Byel ectr
onmi croscopy , l
ipofusci nappear sasintralysosomal el
ectr
on- dense
granulesinper i
nuclearl ocat i
on.Thesegr anulesar ecomposedofl i
pid-prot
ein
compl exes.Lipofuscinr epr esentst hecollecti
onofi ndigesti
blematerialinthe
l
y sosomesaf terintr
acel lularlipidperoxidation.
  Byli
ghtmi croscopy ,thepigmenti scoarse,gol
den-br
owngr anularandoften
accumulatesi nthecent r
alpar tofthecellsaroundthenuclei
.
 Byelect
ronmi croscopy,l
ipofusci nappearsasintr
alysosomal granul
es.
Li
pofuscinrepr esentsthecollectionofindigest
ibl
emat eri
ali
nt helysosomes
aft
erint
racellularli
pidperoxi
dat ion.

EXOGENOUSPI GMENTS
 Exogenouspi gment sar ethepi gmentsintroducedi ntothebodyf rom outside
suchasbyi nhalation,ingest
ionori noculati
on.
I
nhal
edPi gment s
 Thel ungsofmosti ndi
v i
duals,especial
lyoft hoselivi
nginur banar easduet o
atmospher icpollutantsandofsmoker s,showal ar
genumberofi nhaled
pigment edmat erials.Themostcommonl yinhaledsubst ancesar ecarbonor
coaldust .
 Thepi gmentpar ticlesafteri
nhal ati
onar etakenupbyal veolarmacr ophages.
Someoft hepigment -l
adenmacr ophagesar ecoughedoutv iabronchi,whi
le
someset tl
einthei ntersti
ti
al t
issueoft helungandi ntherespiratory
bronchioles.
 Ant hracosis(i.
e.deposi t
ionofcar bonpar t
icles)isseeni nalmostev eryadult
l
ungandgener allypr ovokesnor eacti
onoft issueinjury.

I
ngest
edPigment s
 Chronicleadpoisoningmayproducethechar
acter
isti
cbluel
inesonteet
hat
t
heguml i
ne.
 Carotenaemiaisy el
l
owish-
redcolour
ati
onoftheskincausedbyexcessi
ve
i
ngesti
onofcarrotswhichcontai
ncarot
ene.

I
nject
edPi gments(Tatt
ooing)
 Pigmentsli
keIndiainkareint
roducedi
ntot
hedermisinthepr
ocessof
tatt
ooingwherethepi gmenti
stakenupbymacrophagesandli
espermanent
ly
intheconnecti
vetissue.

EXTRACELLULARMATRI
XCHANGES.
ABNORMALACCUMULATI ONSI
NEXTRACELLULARMATRI
X

Hy
ali
nechange
 ‘hyali
ne’meansglassy(hy al
os=glass)
 Hy ali
neisadescri
ptiv
ehi stol
ogictermforglassy
,homogeneous,eosi
nophi
l
ic
appearanceofmateri
alinH&E- st
ainedsecti
onsanddoesnotrefertoany
speci
ficsubst
ance

Ext
racel
lularhy ali
ne
 Cor pusal bicansovari
i
 Hy ali
nisedol dscaroffibrocoll
agenoustissues
 Hy ali
near teriol
oscl
erosisinrenal v
essel
sinhypertensionanddiabet
es
mel li
tus
 Hy ali
nisedgl omeruli
inchr oni
cgl omerul
onephri
ti
s
Normalov ary
 att heonsetofeachov ariancycle,anumberofpr i
mar yfol
li
clesbegi
ntogr
ow
 andmat ure
 usual l
y,only1f oll
icl
er eachesf ullmat urityandonly1oocy t
eisdischarged
 afterov ul
ationt hefoll
icularwallscollapseanddev el
opintothecor pusluteum
 iftheoocy tei sfert
il
ized,thecor puslut eum enlargestof orm acorpusluteum
ofpr egnancy
 iftheoocy tei snotfertil
i
zed, t
hecor pusl uteum degeneratesin10-12day s
afterov ul
ationandf or mst hecor puslut eum ofmenst ruati
onandi s
transformedi nt
oawhi tescar,thecor pusal bi
cans
Cor
pusalbicansov ari
i
 isther egressedf orm oft hecorpusl uteum
 isanexampl eofphy siologi
cext r
acel lularaccumulationofhy aline
 appear sasl ar
gepal epi nkhomogenousst ructurewi thirr
egularbor ders

Hy
ali
near terioloscl erosis
 Hy alinescl er osisisacommonar teriolarlesi onthatmaybeseen
physiological lyduet oaging,
 ormayoccurpat hological l
yinbeni gnnephr oscler
osi
sinhy pert
ensivesandas
apar tofmi cr oangiopathyi ndiabetics
 Thel esionsr esultmostpr obablyfrom l eakageofcomponent sofplasma
acrosst hev ascul arendot helium
 Theper meabi li
tyoft hev essel wallisi ncreased, duetohaemody anamicstress
i
nhy per tensionandmet abol i
cst r
essi ndi abetes,sothatt
hesepl asma
component sl eakoutandgetdeposi tedint hevesselwall
 Thev isceral ar teri
olesarepar ti
cularlyinv olved
 Thev ascul arwal lsarethi ckenedandt hel umi nanarr
owedorev enoblit
erat
ed
 Mi croscopi cal l
y ,
thet hi
ckenedv essel wal lshowsst r
uctur
eless,eosinophil
i
c,
hyali
nemat er i
al i
nt heintimaandmedi a

Amyl
oidosi s
 thet erm usedf oragr oupofdi seaseschar acter i
sedbyext racel l
ular
deposi t
ionoff i
bril
larpr oteinaceoussubst ancecal ledamy loid
 hav i
ngcommonmor phologi cal appear ance, stainingpr oper tiesandphy si
cal
st ruct ure
 butwi thv ariablepr otein( orbi ochemi cal
)composi tion
 namedbyVi rchowas‘ amy loid’ undert hemi st akenbel iefthatt hemat eri
alwas
st arch- l
ike( amy lon=st arch) .
 Gr ossl y,theaf f
ectedor gani susual l
yenl arged, paleandr ubber y.Cutsur f
ace
showsf i
rm, waxyandt ransl ucentpar enchy mawhi cht akesposi tivestaini
ng
wi tht hei odi net est(amy l
oi dst ainesbr ownwi thi odineandt urnesv i
oleton
addi t
ionofdi lutesulfur i
caci d)
 ByH&Est ainingunderl i
ghtmi cr oscopy ,amy loidappear sasext r
acel l
ular,
homogeneous, st r
uctur el
essandeosi nophi l
ichy alinemat erial
 itst ainsposi t
ivewi thCongor edst ainingandshowsappl e-gr eenbi refri
ngence
onpol arisingmi croscopy
 allf ormsofamy loidar esi mi l
ari nappear ance, butt heyarechemi cal
ly
het er ogeneous
 amy l
oi discomposedof2mai nt ypesofcompl expr oteins:
 I.Fi brilprot einscompr i
seabout95%ofamy loid
 II.Non- fi
br i
llarcomponent swhi chincludeP- componentpr edomi nantl
y
  ByX- raycr ystallographyandi nfra-
redspectroscopy,thef
ibr
ilsareshownt o
hav ecr oss- β-pleatedsheetconf igurat
ionthatgivesthecharacter
ist
icstaini
ng
proper t
iesofamy loidwi t
hCongor edandbirefr
ingenceunderpolari
sing
mi croscopy .
 Chemi calanal y
si soffibri
l pr
oteinsofamyloidrevealshet
erogeneousnat ure
ofamy loid
 thesepr ot
einscanbecat egor
isedasunder :
 i
)AL( amy loidlightchai n)protei
n
 i
i)AA( amy loi
dassoci ated)protein
 i
ii)Ot herpr oteins

Deposi
ti
onofALAmy l
oid
 Thest imul usforpr oduct i
onofALamy loi
dissomedi sorderof
i
mmunogl obulinsy nthesise.g.multi
plemy eloma, Bcellly
mphoma.
 Excessi veimmunogl obuli
npr oduct
ionisinthef or m ofmonocl onal
gammopat hyi.e.ther eisproducti
onofeitheri ntactimmunogl obulin,orλlight
chain, orκl i
ghtchai n, orr
arelyheavychains.
 Partialdegr adationint heform ofli
mitedprot eolysi
sofl argerprotein
molecul esoccur sinmacr ophagest hatareanat omi call
ycloselyassociated
withALamy l
oid.
 Non- fi
bril
larcomponent splaysomer olei
nf oldingandaggr egati
onoff ibri
l
proteins.

Deposi
ti
onofAAAmy l
oid
 AAamy l
oidisdirect l
yr elatedt oSAAl (
ser um amyloi
d-associatedprotei
n)
l
ev el
s, ahighdensi tyl i
popr otein.SAAissy nt
hesi
sedbyt hel i
verinresponseto
cytokines,notablyi nterleukin1and6, r
eleasedf r
om activatedmacr ophages.
 Thel evelsofSAAar eel evatedi nlong-
standingti
ssuedest ructione.g.i
n
chronicinflammat i
on, cancer s.Howev er,SAAl evel
sinisolati
ondonotal ways
l
eadt oAAamy loid.
 Asi nALamy l
oid, parti
aldegr adationi
nt heform ofli
mitedpr oteol
ysistakes
placei nreti
culoendot hel i
al cell
s.

Amyl
oidosi
s-classifi
cation
 Basedoncause, intopr i
mary(AL)
 andsecondar y-asacompl i
cat
ionofsomeunder l
yi
ngknowndisease,
reacti
ve/i
nflammat ory(AA)amy l
oidosi
s
 Basedonext entofamy l
oiddepositi
on,i
ntosyst
emic(
gener
ali
sed)invol
vi
ng
mul t
ipl
eorgansand
 local
isedamy loi
dosi sinvol
vi
ngoneort woorgansorsi
tes

I
rr
ever
sibl
ecel
lul
ari
njur
y.Necr
osi
s–t
ypes.Apopt
osi
s.

Whenthestr
essi
smildtomoderate,t
heinjur
edcel
lmayr
ecover(r
eversiblecell
i
njur
y),
whil
ewhentheinj
uryi
spersist
entcell hmayoccur(
deat i
rr
eversiblecell
i
njur
y).

Withper
sist
entorexcessi
venoxi
ousexposur
es,
inj
uredcel
l
spassanebul
ous“
poi
nt
ofnoret
urn”char
acteri
zedbythr
eephenomena:
 1)theinabi
l
itytorestoremit
ochondr
ialf
uncti
on(ATPgenerati
on)ev
enaf
ter
r
esolut
ionoftheorigi
nal i
njury
;
2)thelossofstructureandf
uncti
onsoftheplasmamembr aneand
i
ntr
acell
ularmembranes;
3)andt hel
ossofDNAandchr omati
nstruct
urali
ntegr
it
y.

Twotypesofcel
ldeath,whichdiff
erintheirmor phology,mechani sms,androlesin
di
seaseandphysi
ology
– necr
osis
 “premature”or“unti
mel y”deathduet o“causes”
 alway spathol
ogic(ischemia,toxins,var
iousinfecti
ons,tr
auma)
– apopt
osis
 “normal”death:whenacel l
isdepr iv
edofgr owt hfact
orsorthe
cell'
sDNAorpr ot
einsaredamagedbey ondr epair
,thecel
l ki
l
ls

Necrosis
 Al ocaldeat hofcel l
s,ti
ssues,partofanor gan,andsomet i
mesanent i
reorgan
i
nl ivi
ngor gani sm
 Twoessent ial changescharacteriseirr
eversibl
ecellinj
uryinnecrosisofall
types:
i
)Denat urati
onofpr ot
eins.Thispr ocessismor phological
lyseenas
characteristi
cnuclearchangesi nnecroticcell.
i
i)Cel ldigestionbyl yt
icenzymes.Mor phol ogi
call
ythischangei sidenti
fi
edas
homogeneousandi ntenselyeosinophili
ccy t
oplasm.Occasi onall
y,itmayshow
cytopl
asmi cvacuolat i
onordy str
ophiccal ci
fi
cation.
Theenzy mesr esponsi
blefordigest i
onoft hecellsarederi
v edeitherfr
om the
l
ysosomesoft hedy ingcellsthemselv esorfrom t hel
ysosomesofl eukocytesthat
arerecruitedaspar toft heinfl
ammat oryreacti
ont ot
hedeadcel l
s

I.Nuclearchanges
1.Karyopy knosis–chromat i
ncondensati
on(thenucleusi
sshr unk,
small
er,
deeplybasophil
icwi t
hchr omati
nclumpedalongt henuclearmembrane).
2.Karyorrhexis-fragmentat
ioni
ntonuclearpart
icles.
3.Karyolysis-chr omati
ndissol
uti
on.In1t o2day s,t
henucleusinadead
cell
maycompl etelydisappear
.

II
.Cy t
oplasmicchanges:
1.Homogenouscy toplasm
-desi ntegr
ati
onofor ganels
-t helossoflight
erstaini
ngglycogenpart
icles
2.Highlyeosinophil
ic:attr
ibut
ablepart
lyt
oi ncr
easedbindi
ngofeosint
odenatur
ed
cytopl
asmi cprotei
nsandpar tl
ytolossofbasophil
icr
ibonucl
eicaci
d(RNA)i
nthe
cytopl
asm

Dependi
ngonthepat
hogenicmechani
sms,
causesandt
issuel
ocat
ion,
ther
ear
efi
ve
mainpat
ter
nsofnecr
osis:
 COAGULATIVENECROSIS
 LI
QUEFACTIVENECROSIS
 CASEOUSNECROSI S
 FATNECROSIS
  FI
BRI
NOI
DNECROSI
S

Coagulat i
venecr osi
s( CN)
 CNusual lydev elopswhent hemai npat hogeni cmechani sm isdenatur ati
onof
proteinsandbl ockedpr oteolysis.
 I tisthemostcommont y peofnecr osis, mainl ychar acterist
icofhy poxi cdeath
ofcel l
si nalltissuesexceptbr ain-my ocar dium, kidney ,spleen( ti
ssues
cont ainingl argeamount sofpr oteinsandsmal lamount sofwat er).
 Gr oss:necr oti
car eaisshar plydemar cat edf rom t headj acenttissue, grayi
sh-
whi t
et oy ell
owi ncol our
, sl
ightlypromi nentandf irm.
 I tissur roundedbysocal l
edhemor rhagi c–hy per aemi czone ( or
demar cat i
onzone) .
Hist
ology :thehi stol
ogi cf eatur
esdonotbecomeev i
dentunt i
l8–12h.Despi teof
nucl
earl oss, ther eispr eserv at
ionoft hebasi cout li
neoft henecr oti
ccel l
sf oratleast
someday sandt heref oreshadowsofpr e-
exi stingst ruct urescanbeseen.
 Denat ur ationofpr oteinaf f
ectsal soenzy mi cpr ot einsandcel ldigestionand
l
iquef act i
onf ail tooccur .
 Lat ely, thenecr osedf ocusi sinf i
l
tratedbyi nflammat or
ycel lsandt hedead
cellsar ephagocy tosedl eavinggr anulardebr isandf ragment sofcel ls.

LI
QUEFACTION( COLLIQUATI VE)NECROSI S
 Necroti
cdegr adat
ionoftissuethatsoft
ensandbecomesl i
quefi
ed
 Lysosomal enzymesr el
easedbynecr ot
iccel
l
sorneutrophi
lscause
li
quefact
ionoft i
ssue
 Thecommonexampl esareinfarctbr
ainandabscesscavi
ty

 Grossly,t
heaffectedareaissoftwit
hliquef
iedcentrecontai
ningnecrotic
debri
s.
 Later
,acy stwalli
sformed.
 Microscopical
ly,t
hecysticspacecontainsnecr
oticcell
debrisand
macrophagesf il
l
edwithphagocy t
osedmat eri
al.
 Thecy stwalli
sformedbypr oli
fer
ati
ngcapill
ari
es,inf
lammat orycel
l
s, and
gl
iosis(prol
if
erati
nggli
alcell
s)inthecaseofbrainandpr ol
if
erati
ng
fi
broblast
sinthecaseofabscesscav i
ty.

Caseousnecr osis
 from lat i
n-caseum=cheese
 mostcommoni tisencount eredi nsomei nfections-tuber culosi
s!
 Incaseousnecr osis,
unlikecoagul ati
venecr osis, t
henecr oticcell
sdonot
retaint heircellularoutl
i
nes, buttissuei snotliquef i
edasi nliquefacti
ve
necr osis
 Gr ossly ,
foci ofcaseousnecr osis,ast henamei mpl i
es,resembl edrycheese
andar esof t,
gr anularandy ell
owi sh.
 Mi croscopi cally,thenecr osedf oci arestructureless,eosinophili
c,andcontai
n
granul ardebr is.
 Thesur roundi ngt i
ssueshowschar acteri
sti
cgr anulomat ousi nfl
ammat or
y
react i
onconsi stingofepi theli
oidcel l
swi thinterspersedgi antcell
sof
Langhans’ t
ypeandper ipher almant l
eofly mphocy t
es.

FATNECROSI
S
 aspecial f
orm ofcelldeathoccurr
ingattwoanat
omi
cal
l
ydi
ff
erentl
ocat
ions
butmor phological
lysi
mi l
arl
esions.
Thesear e:
 foll
owingacut epancreati
cnecrosis,
 traumati
cf atnecrosi
scommonl yinbreast
s.

PANCREATI CFATNECROSI S
 Liberati
onofpancr eati
cli
pasesfrom inj
uredori nflamedt i
ssuethatresultsi
n
necr osi
soft hepancr easaswellasoft hefatdepot sthr
oughouttheper i
toneal
cav i
ty
 Fatnecr osishy drolysesneutr
alf
atpr esentinadi posecellsint
oglyceroland
freef at
tyacids
 Thel eakedoutf r
eef attyaci
dscompl exwithcalci um toform cal
cium soaps
(saponificati
on)
 Gr ossly,fatnecrosisappearsasy ell
owish-whiteandf i
rm deposi
ts.
 For mationofcal cium soapsimpar t
sthenecr osedf ocif
ir
merandchal kywhi t
e
appear ance.

Fi
bri
noidnecr osis
 Fibr
inoidnecr osisisassociatedwiththeaccumul at
ionoffibr
inoid.
 Pathogenesi sisassoci at
edwi t
hdisturbanceofi mmuni t
yandi ncreased
vascularper meabilit
yin
 autoimmunedi seasesofconnect iv
et i
ssue;
 malignantf orm ofhy pert
ensi
on;
 chronicgast r
iculcer.
 Histology:deposi t
ionoff i
bri
n-l
ikeproteinaceousmateri
al-abr i
ghtpinkand
amor phousappear anceinH&E
 Necrot i
cfocusi ssur r
oundedbynucl eardebrisofneutr
ophils

Cl
inical -anat omi calf or msofnecr osis:gangrene
 Necr osi soft issuesi ncont actwi thoutsideenvir
onment
 I tisnotadi st inctivepat ternofcel l
death,buttheter mi sstil
lcommonl yused
i
ncl i
nical pr act ice
 Usual lyref er st ot hecondi tionofal i
mb( general
lyt hel owerl eg)t hathasl ost
i
t sbloodsuppl yandhasunder gonecoagul ati
venecr osisinvol vi
ngmul tiple
tissuel ay ers
Dr
ygangr ene
 Gr ossly ,theaf fect edpar tisdr y,shrunkenanddar kbl ack,resembl i
ngthef oot
ofamummy .
 Thel ineofsepar ationusual lybringsaboutcompl et esepar ati
onwi thevent ual
falli
ngof foft hegangr enoust issueifitisnotremov edsur gically.
Wetgangr ene
 Whenbact er i
al infect i
oni ssuper imposed, t
hemor phol ogicappear ance
changest ol iquef act ivenecr osisbecauseoft hedest ructi
vecont entsoft he
bact eri
aandt heat tractedleukocy t
es
 Gr ossly ,theaf fect edpar tissof t,swoll
en,putri
d,rot t
enanddar k.
 Thel ineofdemar cat i
onbet weengangr enoussegmentandv iabl
ei sgener all
y
notcl ear -
cut .
 Di abeticf ooti sex ampl eofwetgangr eneduet ohi ghsugarcont enti nthe
necr osedt issuewhi chfavour sgr owthofbacteri
a.
  Wetgangr
eneal
sooccur
sinnatur
all
ymoi
stt
issuesandor
ganssuchast
he
mouth,
bowel
,l
ung,
cervi
x,v
ulv
aetc.

Decubi
tusul cer
 =pressuresore
 l
ocalizeddamaget otheskinand/ orunder l
yingti
ssuethatusuall
yoccurovera
bonypr ominenceasar esultofpressure
 Themostcommonsi tesaret heskinoverly
ingthesacrum, coccy
x,heel
sor
thehips,butothersi
tessuchast heel bows,knees,ankles,
backofshoulders,
orthebackoft hecranium canbeaf fected.

Sequest
rum
 Api eceofnecrot
icti
ssue,
usuall
ybone,whichhasbecomeseparat
edf
rom t
he
surroundingheal
thyti
ssue
 deadbonel y
ingwit
hinacavi
tyorabscessasaresul
toflong-
ter
m
osteomy eli
ti
s

Out
comeofnecrosi
s
– Inflammation–l i
neofdemarcati
on
– Or gani
sati
on
 Granulat
ionti
ssue cicat
ri
x(connect
ivet
issue)
 li
quefact
ivenecrosi
s(brai
n)–pseudocyst(gl
ial
capsul
e)

APOPTOSIS
Apoptosi
sisafor
m of‘coor
dinatedandi nt
ernal
lyprogrammedcel ldeat
h’hav
ing
si
gnif
icancei
navari
etyofphysiologicandpathologiccondit
ions
– Whenacelli
sdeprivedofgr owthfact
or s
– ort
hecell
'
sDNAorpr oteinsaredamagedbey ondrepai
r

Thechar acteri
sticmor phologicchangesi napopt osisseeninhistologicand
elect
ronmi croscopicexami nati
onar easunder :
1.Invol
vementofsi nglecel l
sorsmal lclustersofcell
sinthebackgr oundof
vi
ablecells.
2.Theapopt ot i
ccellsarer oundtoov al shr
unkenmassesofi ntensel y
eosinophili
ccytoplasm (mummi f
iedcell)containi
ngshr unkenoralmost -
normal
organell
es.
3.Thenucl earchromat iniscondensedorf ragment ed(pyknosisorkar yorrehexi
s).
4.Theremaybef ormat i
onofmembr ane-boundnearspher i
cal bodiesonor
aroundthecel lcaledapopt
l oticbodi escontainingcompact edorganelles.
5.Characteristi
call
y,unli
kenecr osis,thereisnoacut einf
lammat oryreact
ion
aroundapopt osis.Phagocy tosisofapopt oti
cbodi esbymacr ophagest akesplaceat
varyi
ngspeed.

 Physiologic/normal
/:servestoel
iminatepot
ential
lyharmfulcel
l
sandcel
l
s
thathaveout li
vedt
heiruseful
ness
 Pathologic:whencell
saredamagedbey ondrepair
,especi
all
ywhenthe
damageaf fect
sthecell
'
sDNAorpr ot
eins

PHYSI
OLOGI
CAPOPTOSI
S
  Duringembr yogenesis:el
i
mi nat
ionofpot enti
all
yharmf
ulsel
f-r
eact
ive
l
y mphocy t
es
 Turnoverofpr ol
ifer
ati
vetissues(e.
g.,i
ntesti
nalepi
thel
i
um, l
ymphocytesi
n
bonemar r
ow, andthymus)
 I
nv olut
ionofhor monedependentt i
ssues( e.
g.,
endometri
um)
 Declineofleukocy t
enumber sattheendofi mmuneandi nfl
ammatory
responses

PATHOLOGI
CAPOPTOSI
S

 DNAdamage
 Accumul at
ionofmi sfol
dedpr otei
ns
 Inf
ections,
especiall
ycertainvir
alinfect
ions
 Afterductobstr
uctioninthepancr eas,parot
idgl
and,andki
dney
 Apoptosisisregulatedbybi ochemicalpathwaysthatcont
rolt
hebalanceof
death-andsurvival-
inducingsignalsandul t
imat
elytheact
ivat
ionofenzymes
caledcaspases.
l

Aut
ophagy
 Aut ophagyisanadaptati
ont onutr
ientdepri
vat
ioninwhichcel
lsdigestt
hei
r
ownor ganell
esandrecy
clethem topr ov
ideenergyandsubstr
ates.
 Ifthest r
essistoosever
ef ortheprocesstocopewithit
,itr
esult
sincell
death
byapoptosis.

HAEMODINAMICDI
SORDERSPARTI.
HYPERAEMIAANDCONGESTI
ON,HAEMORRHAGES

HOMEOSTASI
S
 Themechani
sm bywhi
cht
heconst
ancyoft
hei
nter
nal
env
ironmenti
s
 maintainedandensur edi scall
edt hehomeost asi
s.
 Thenor mal composi tionofinternal envi
ronmentconsi st
softhefoll
owing
component s:WATERandELECTROLYTES.
 Thetotal bodywat eri nanor mal adultmalecompr i
ses50-70%(average60%)
ofthebodywei ght; distr
ibutedinto2mai ncompar t
mentsofbodyf l
uids
separatedf rom eachot herbymembr anesfreelypermeabletowater:
 i
)Intracellularfluidcompar tment .Thiscompr i
sesabout33%oft hebody
weight.
 i
i)Extracellularfluidcompar t
ment .Thisconstit
utestheremaini
ng27%of
bodywei ghtcont ainingwat er.

EXTRACELLULARFLUI D
4subdi
v i
sionsECF:
 I ntersti
tialflui
di ncludingl ymphf l
uidconst
itutesthemaj orpr oport
ionofECF
(12%ofbodywei ght ).
 I ntr
avascul arfluidorbl oodpl asmacompr i
sesabout5%oft hebodywei ght.
 Mesenchy malt issuessuchasdenseconnect iveti
ssue, car t
ilageandbone
containbodywat ert hatcompr isesabout9%oft hebodywei ght.
 Tr anscel l
ularfluidconst itutes1%ofbodywei ght.Thisi st hef lui
dcontainedin
thesecr eti
onsofsecr etorycellsoft hebodye. g.skin,sal i
v aryglands,mucous
membr anesofal iment aryandr espir
ator
ytracts,kidney s, gonads, t
hyroid…
 Theessent ialdiffer
encebet weent hetwomai nsubdi visionsofECFi sthe
higherpr oteincont entint hepl asmat haninthei nt
er st
itial fl
uidwhichpl aysan
i
mpor t
antr oleinmai ntainingfluidbalance.

 Effectiveoncot i
cpressur eist hedi ffer encebet weent hehi gheroncot i
c
pressur eofpl asmaandt hel oweroncot icpr essur eofi ntersti
ti
al fluidandi s
thefor cet hatt endstodr awf luidi ntot hev essel s.
 Effectivehy drostati
cpr essur ei st hedi ffer encebet weent hehi gher
hydrost aticpr essureinthecapi l
lar yandt hel owert i
ssuet ension; itisthef orce
thatdr i
v esf l
uidt hr
ought hecapi l
lar ywal lintot heinterstiti
alspace.
 Atthear teri
olarendoft hecapi l
l
ar y,t hebal ancebet weent hehy drost atic
pressur e( 32mm Hg)andpl asmaoncot icpr essur e(25mm Hg)i st he
hydrost aticpr essureof7mm Hgwhi chi st heout war d-drivi
ngf or cesot hata
smal lquant ityoff l
uidandsol ut esl eav et hev essel toent erthei nter sti
tial
space.
 Atthev enul arendoft hecapi llary,thebal ancebet weent hehy drost atic
pressur e( 12mm Hg)andpl asmaoncot icpr essur e(25mm Hg)i st heoncot i
c
pressur eof13mm Hgwhi chi st hei nwar d- drivi
ngf orcesot hatt hef lui
dand
solutesr e-entert heplasma.
 Thet issuef luidleftafterexchangesacr osst hecapi l
larywal lescapesi ntothe
l
y mphat icsf rom wher eitisf inallydr ainedi ntov enousci rculation.
 Tissuef act orsi .
e.oncoticpr essur eofi nter stit
ialfl
uidandt issuet ension,are
normal lysmal landinsignificantf orcesopposi ngt hepl asmahy drost at
ic
pressur eandcapi l
l
aryhy drost aticpr essur e,respect i
vely.

OEDEMA
 TheGr doi
eekwor demameansswel
l
ing.
 Oedemamaybedef inedasabnor mal andexcessi veaccumul ati
onof“ f
ree
fl
uid”i
nt hei nt
er sti
ti
al t
issuespacesandser ouscav it
ies(effusions).
 Effusi
onsar eclassifi
edast r
ansudat iv
eorexudat ive.
 Transudatesr esultfrom ani mbal anceofhy drostaticandoncot i
cpr essure,as
occursincongest ivehear t
sf ai
lure,cir
rhosi
sandt henephr oticsy ndrome.
 Thesef l
uidshav eal owspeci fi
cgr avit
yandal owpr otei
nconcent rati
on.
 Exudatesr esultfrom i njurytothemesot heli
um, aswi thinfections,lupusor
rheumatoidpl eur i
ti
s, pancr eati
ti
s, r
adiati
on,ormal ignanttumour s.
 Thesef l
uidshav eahi ghspeci f
icgr avi
ty(>1.015)andahi ghpr otein
concentration(>3g/ dl)andcont aininfl
ammat orycel l
s.

TRANSUDATES
(Fr
eefl
uidi
nbodycav i
ties)
 asci
tes(peri
tonealcavit
y),
 hydr
othoraxorpleuraleffusi
on(pl
euralcavit
y),
 hydr
opericar
dium orpericardi
alef
fusi
on( peri
cardi
alcav
ity
).

Fr
eeflui
dininter
sti
ti
alspace
 Theoedemaf lui
dli
esfreeintheint
ersti
ti
alspacebetweent
hecel
l
sandcan
bedispl
acedf r
om oneplacetoanother.
 Inthecaseofoedemai nthesubcutaneousti
ssues,momentar
ypr
essur
eof
fi
ngerproducesadepressionknownaspi t
ti
ngoedema.

PATHOGENESI SOFOEDEMA
1.Decr easedplasmaoncot i
cpr essur e:decr easedsynthesi
s( e.g.,
li
verdi
sease,
proteinmal nutr
it
ion)orincreasedl oss( e.g.,nephroti
csyndrome)
2.Increasedcapi l
lar
yhy drostat
icpr essur e:e.g.,
heartfai
lur
e
3.Ly mphat i
cobst r
ucti
on: e.
g.,i
nflammat ionorneopl asia
4.Tissuef actor
s( i
ncreasedoncot icpr essur eofinter
stit
ial
fluid,anddecr
eased
ti
ssuet ension):
5.Increasedcapi l
lar
yper meabili
ty:e.g.,inflammat ion
6.Sodi um andwat erretenti
on:e.g.,renal fail
ure

OEDEMATYPES
1.Local i
sedwhenl i
mitedtoanor ganorl
imbe.g.Lymphati
coedema,
i
nflammat or
yoedema, all
ergi
coedema.
2.Gener ali
sed(anasar
caordr opsy)wheniti
ssystemici
ndist
ribut
ion,
par
ti
cul
arl
y
noticeableinthesubcutaneousti
ssuese.g.r
enaloedema,car
diacoedema,
nutrit
ionaloedema.

HAEMODYNAMI CDI SORDERS

 Thepr inci
plesofbl oodf l
owar ecal
ledhaemody nami cs.
 Nor mal ci
rculatoryf uncti
onr equir
esuni nterruptedf l
owofbl oodf r
om thelef
t
ventri
cletot hef arthestcapi l
l
ariesi
nt hebody ;r
eturnofbl oodfrom systemic
capill
arynetwor ki ntother i
ghtv ent
ricle;andf r
om t her i
ghtventr
icl
etot he
fart
hestpul monar ycapi l
l
ariesandbackt ot heleftatrium.
Derangement sofbl oodf loworhaemody nami cdisturbancesar econsider
ed
under2br oadheadi ngs:
 Di sturbancesi nt hev olumeoft hecirculati
ngbl ood.Thesei nclude:
hyperaemi aandcongest ion,haemor rhageandshock.
 Ci
rcul
ator
ydisturbancesofobst
ruct
ivenat
ure.Thesear
e:t
hrombosi
s,
embol
ism,ischaemiaandinfar
cti
on.

Hy
per aemi aandCongest ion
 bot hst em f rom locall
yi ncreasedbl oodv olumes
 Hy per aemi ai sanact i
v epr ocessinwhi char teriolardil
ation(e.g.
,atsit
esof
inflammat ionori nskeletal muscledur i
ngexer cise)leadstoi ncr
easedbl ood
flow.Af fectedtissuest urnr ed(erythema)becauseoft heengor gementof
vessel swi t
hoxy genatedbl ood.
 Congest ion: apassi vepr ocessr esulti
ngfrom r educedout fl
owofbl oodf rom a
tissue.I tcanbesy st
emi c,asi ncardiacfai l
ure, orlocal,asinisolat
edv enous
obst ruction.
 Congest edt issuest akeonaduskyr eddi
sh- bluecol or(cyanosis)duetor ed
cell stasisandt heaccumul at
ionofdeoxy genat edhaemogl obin.

Act
iveHy peraemia
 Thedi l
atati
onofarteri
es,
art
eriolesandcapill
ari
esisef
fectedei
thert
hrough
sympat heti
cneurogenicmechani sm orv
iatherel
easeofvasoacti
ve
substances.
 Cli
nicall
y,hyper
aemi ai
scharacter i
sedbyrednessandrai
sedtemperatur
ein
theaffectedpart
.

Congesti
on
Obstr
uctiontothev enousout flowmaybel ocalorsystemi c.
Accor di
ngly,venouscongest i
oni sof2t ypes:
 Local venouscongest ionr esultsf rom obst r
ucti
ont othev enousoutflowfrom
anor ganorpar toft hebody ,outsidepr essureont hev essel wallasoccursin
ti
ghtbandage, plasters,tumour s,pr egnancy,herni
aet c, orintr
aluminal
occlusionbyt hrombosi s.
 Systemi c(General)v enouscongest ionisengorgementofsy stemicveinse.g.
inleft
-sidedandr i
ght-sidedhear tfai l
ure.
 Usuallythefluidaccumul atesupst r eam tothespeci f
icchamberoft hehear t
whichi sini
ti
allyaffected.I nl eft
-sidedhear tfail
urepulmonar ycongest i
on
result
s, whereasi nright-sidedhear tf ai
lur
esy st
emi cvenouscongest ion
result
s.

Congestion
 Asar esultoftheincreasedvolumesandpr essur
es, congestioncommonl y
leadst ooedema.
 Inlong- st
andingchronicpassivecongest i
on,thelackofbl oodf l
owcauses
chroni chypoxia,potenti
all
yresul
ti
ngini schemictissueinjuryandf i
brosis.
 Capi l
laryruptureinchroniccongesti
oncanal socausesmal lhaemorrhagic
foci;subsequentcat aboli
sm ofextravasatedredcellscanl eaveresi
dual
tell
taleclustersofhaemosi deri
n-l
adenmacr ophages.

Acutecongest ionoft hel

ung
 resultofacut efail
ureofthelef
tventr
icl
e(CAD,MI )
.
 Ther esult
ingv enousengorgementofthelungleadst
otheaccumul at
ionofa
t
ransudationi nthealv
eoli-acondi
ti
ontermedpul monaryoedema.
 Gr ossly,t
hel ungsinpulmonaryoedemaar eheavyandmoist.Cutsurf
ace
 exudesf r
othyfluid(mi xt ureofairandf lui
d).
 Microscopicall
y ,theal v eolarcapillari
esar econgested.
 Ini
ti
all
y,theexcessf luidcol l
ectsint heinterst
iti
allungspaces( i
ntersti
ti
al
oedema) .
 Later,t
hef l
uidfil
lstheal veolarspaces( al
veolaroedema) .
 Oedemaf l
uidint heint er sti
tium aswel lasthealveolarspacesappear sas
eosinophil
ic,granularandpi nkpr oteinaceousmat er
ial,
oftenadmixedwi th
someRBCsandmacr ophages.
 Pulmonar yfl
uidaccumul ationmaygounnot i
cediniti
all
y,buteventuall
y
dyspneaandcoughi ngbecomepr omi nent.
 Ift
heoedemai ssev ere, l
argeamount soffrothysput um whichisoftenpink
areexpectorated.
 Hypoxemi aismani f
est edascy anosi s.

Chroniccongest ionoft hel ung

 r esul ts( consequence)ofchr onicfailur eoft hel eftventri
cle( commoncause–
CAD, sur gical valver eplacement ;inthepast-Rheumat i
cmi t
ral stenosi s).
Thei ncr easedpr essur ei nt heal veolarcapi l
lari
eshasf ourmaj or
consequences:
 1. Thei ncr easedhy drost aticpr essur ef orcesf luidf r
om t hebl oodi ntot he
alveol arspaces, resul ti
ngi npul monar yoedema.
 2.Mi crohaemor rhagesr eleaseer yt
hr ocy tesint otheal veolarspaceswher e
theyar ephagocy tosedanddegr adedbyal veolarmacr ophages.Ther eleased
i
roni nt hef orm ofhaemosi deri
n, r
emai nsi nthemacr ophages, whi char ethen
called“ hear tfail
ur ecel ls” .
 3.Thehy poxi ast i
mul at esf ibrosisint heint er
st it
ialspacesoft hel ung.
Histol ogi cal l
y ,t
hesept aar emi l
dlythickenedduet osli
ghti ncreasei nfibrous
connect ivet issue.Thepr esenceoff ibrosi sandi roni sviewedgr ossl yasa
fi
rm br ownl ung( browni ndur ati
on).
 4.Thei ncr easedcapi llar ypr essureist ransmi ttedt othepul monar yar teri
al
syst em, acondi t
ionl abel edpul monar yhy per t
ensi on.Longst andi ng
congest ionandconsequentpul monar yhy pertensi onmaycausepr ogr essive
thi
ckeni ngoft hewal lsoft hepul monar yar ter
iesandar teri
oles.
 Gr ossl y, thel ungsar eheav yandf i
rmi nconsi st ency.Thesect ionedsur faceis
rustybr owni ncol ourr ef erredt oasbr owni ndur ationoft helungs.

Congestionoft heliv
er
result
s:
1.From r
ight-sidedheartfai
lure(massi
vepul
monar ythromboembol
i
sm,
secondar
y
ofpulmonar ydisease)
2.From obstructi
onofi nfer
iorvenacav
aorhepaticveins
(thr
ombosi softhehepat i
cveins-Budd-
Chiar
risy
ndrome)

Acutecongestionoft heliver
 Thehal lmar ksar edistendedwi t
hbl oodcent ralvei
nsandsi nusoidsand
milddisar rayint henor mall
yr adi
alf ashi
onoft hehepati
clamel l
ae.
 Theov er al
lar chi
tectureoft helobulesi spreservedandt hechangesare
rever
sible.
Chroni
ccongest i
onoft heliver
 Bloodflowwi t
hinhepat i
clobulesi
sfrom branchesoft hepor
talvei
nand
 hepaticarteryinport
alar eastowardsacent r
alvei
n.
 Thecent ralporti
onsoft helobulesar
et hel
astareastor eceivebl
oodsupply
andar ethusf i
rsttounder goatr
ophyandnecr osi
swi t
hci r
culator
y
compr omi se.
 Chronicpassi vecongestioncausesatrophyofcentralhepaticcel
lsbyan
i
schemi cpr ocess.
 Centri
lobularnecrosi
sr esultsfr
om exaggerati
onofapr eviouscongest
ive
ci
rculatorydefect.

HEPARMOSCHATUM
 theperiportalhepatocytesmaydev elopfattychange; cutsur faceshows
characteri
sticnutmegappear anceduet or edandy el
lowmot tledappear ance,
correspondingt ocongest edcentreoflobul esandf attyperipher alzone
respectiv
ely.
 Thecent ri
lobularregionsar egrosslyred-br ownandsl i
ghtlydepr essedand
areaccent uatedagai nstthesurroundingzonesoff attyli
ver:nut megl i
ver
(heparmoschat um) .
 Ifchronichepat i
cpassi vecongest i
oncont i
nuesf oral ongt i
me, acondi tion
call
ed" cardiaccir
rhosis"maydev elopinwhi chthereisf i
brosi sbridging
betweencent r
alzonal regi
ons,asshownbel ow,sot hatthepor taltracts
appeart obei nthecent reofthereorganizedl obule.

Haemor r
hage
 adischar geofbl oodf rom thev ascul arcompar tmenttotheext eriorofthe
bodyori ntononv ascul arbodyspaces.
 Ther i
skofhaemor rhage( oftenaf teraseemi nglyinsi
gnif
icanti nj
ury)i
s
incr
easedi nawi dev ariet
yofcl inicaldisor
der scoll
ecti
vel
ycal led
haemor r
hagi cdiatheses: i
nheritedoracqui reddef ect
sinv essel wall
s,
plat
elets,orcoagul ationfactors.
 Extravasationofbl oodi nt
ot het issueswi t
hr esult
antswelli
ngi sknownas
haemat oma.
 Largeext ravasationsofbl oodi ntot heskinandmucousmembr anesarecall
ed
ecchymoses.
 Purpurasar esmal lar easofhaemor rhages(upt o1cm)i ntotheski nand
mucousmembr ane, whereaspet echiaearemi nutepinhead-sized
haemor rhages.
 Largeaccumul ationsofbl oodi noneoranot heroft hebodycav it
iesar
ecall
ed
hemo- thorax,-pericardium, -peritoneum, hemar thr
osis(i
njoints) .

Haemor rhage:pathogenesi s
 Haemor r
hageduet or uptureofthevessel(
Haemor rhageperr hexin).
Themostcommoncausei straumaof t
enbysur geon’sscalpel.
 Haemor r
hagecausedbydamageofv esselwal
ls(Haemor r
hageperdi abrosi
n):
duet oat
heroscl erosis,orinfl
ammat oryorneoplasti
cer osi
onofav esselwal
l.
 Haemor r
hager esult
sf rom damageatt helevelofthecapi l
lari
es
(Haemor rhageperdi apedesi n)
 Incr easedv enouspr essurecauseext r
avasati
onofbl oodfrom capill
ari
esof
thel ung.
 Vi t.“C”defi
ci ency,sev eredecreasethenumberofpl atelet
s
(thrombocy topenia)ordef i
ciencyofacoagulati
onf actorVI I
Iinhemophi l
iai
s
 associ
atedwi
thspont
aneoushaemor
rhagesunr
elat
edt
oanyappar
ent
tr
auma.

Thecl
i
nical
signif
icanceofhaemor rhagedependson:
– t hevolumeand
– r at
eofbl oodl oss
 r apidremov al ofasmuchas20%oft hebloodv olumeorsl ow
lossesofev enlargeramount smayhav eli
ttl
eimpactinheal t
hy
adults;
 gr eaterlossescancausehaemor r
hagic(hypovolemic)shock
– Thesi teofhaemor rhage
 I nsubcut aneoust issues/inthebrain
– Dur ati
on
 chr onicorr ecurrentexternalbloodloss(e.
g.,apepticulceror
menst rualbleeding)causesanetl ossofiron,f
requentl
y
culminatingi nani r
ondef i
ciencyanemi a.

CI
RCULATORYDI
STURBANCESOFOBSTRUCTI
VENATURE

HAEMOSTASI SANDTHROMBOSI S
 Nor mal haemost asiscompr isesapr eciselyregulatedpr ocessinvolving
platelets, clotti
ngf act ors,andendot heli
um thatoccur satt hesi t
eofv ascul ar
injuryandcul minat esi nthef ormat i
onofabl oodcl otthatlimit
sbl eedingf rom
ani njuredv essel .
 Thepat hol ogiccount erpartofhaemost asisist hr
ombosi s.
 Thr ombosi si sthepr ocessoff ormat i
onofsol i
dmassi nci r
cul
ationfrom t he
const it
uent soff lowingbl ood( vary i
ngpr opor t
ionsofcoagul at
ionfact ors,
RBCs, andpl atelets)wi thi
nnon- traumat ized,intactvessels;
 themassi t
sel fiscal edat
l hrombus.
 Abl oodcl otist hemassofcoagul atedbl oodf ormedi nvitroe.
g.inat esttube.
 Haemat omai st heext ravascul araccumul at
ionofbl oodcl ote.
g.intot he
tissues.
 Haemost aticpl ugsar ethebl oodcl otsfor medi nhealthyindivi
dualsatt hesi t
e
ofbl eedi nge. g.ini nj
ur ytot hebl oodv essel.

VI
RHOW’ STRI AD
 endotheli
alinj
ury,
 al
teredbloodf l
ow,
 hypercoagulabi
li
tyofbl
ood.

ENDOTHELI
ALINJURY
 Isofmaj
orsi
gni
fi
cancei
nthef
ormat
ionofar
ter
ial
thr
ombi
andt
hrombi
oft
he
heart
.

 Anydist
urbanceinthedynamicbal
anceoft
hepr
o-andant
i-
thr
ombot
icef
fect
s
ofendot
heli
um
– notonlyphysical
“damage”

 Si
gni
fi
cantendot
hel
i
aldy
sfunct
ion(
int
heabsenceofendot
hel
i
alcel
ll
oss)
mayoccur
 – hy per
tensi
on,
– turbul
entflowoverscar
redv al
ves,
– orbyt heacti
onofbacteri
alendotoxins
Factor
sandconditi
onsthatmaycausev asculari
njur
yandpr
edi
sposet
othe
for
mat i
onofthr
ombi:

 Endocar dialinjur
yinmy ocar diali
nf arction,my ocardit
is,cardiacsurgery
,
pr
osthet icv alv
es.
 Ulcerat edpl aquesi nadv ancedat her osclerosi s.
 Haemody namicst ressi nhy pert
ensi on.
 Ar ter
ial diseases.
 Diabet esmel li
tus.
 Endogenouschemi cal agent ssuchashy per cholesterol
aemi a,endotoxi
ns.
 Exogenouschemi cal agent ssuchasci garet tesmoke.
ALTERATI ONOFBLOODFLOW
I
nt hr
ombosi snor mal axi al f
lowofbl oodi sdistur bed.Whenbl oodslowsdown,
thebloodcel l
sincludingpl atel
et smar gi natetot heper i
pheryandf or
m akindof
pavementcl oset oendot hel i
um ( mar ginat i
onandpav ement i
ng).
TURBULENCE:cont ri
but est oar t
eri
al andcar diact hrombosi s
– Ul ceratedat her oscleroticpl aques,aneur ysmas
STASI S:
cont ri
butestot hedev elopmentofv enoust hrombi
– Sl uggishbl oodf lowduet oprolongedbedr estorsit
ti
ng.

HYPERCOAGULABI LITY:anyt
hingwhi chaccelerat
esthecascade,ori
nhibi
tsi
ts
i
nhibitors
Hyper coagulabi
li
tymayoccurbyt hefoll
owingchangesi nthecompositi
onof
bl
ood:
 I ncreaseincoagul ati
onfactor
se.g.fibri
nogen,prot
hrombin,f
actorVII
a,VI
II
a
andXa.
 I ncreaseinplateletcountandtheiradhesiveness.
 Decr easedlev sofcoagul
el ati
oninhibit
orse.g.Anti
thr
ombinIII
,fi
bri
nspli
t
product s.

Predisposi ngFact ors

Anumberofpr i
mar y(genet i
c)andsecondar y(acquir
ed)f
act
orsfav
our
thr
ombosi s.
 Pr i
mar y( Genet ic)factors:
i
)Def iciencyofant ithrombi n,pr
otei
nCorS
i
i)Def ect sinf ibrinolysis
 Secondar y(acqui r
ed)f actors:
a)Riskf act ors:
i
)Adv ancedage
i
i)Pr olongedbed- rest
i
ii)Immobi l
isation
i
v )Cigar ettesmoki ng
 b)Cl inicalcondi ti
onspr edisposingtot hr
ombosi s:
i
)Hear tdi seases( e.g.my ocardiali
nfarct
ion,CHF,
rheumat icmi tral stenosis,cardi
omy opathy)
i
i)Vascul ardi seases( e.
g.at her
osclerosi
s,aneurysmsoftheaor
taandot
her
vessels, var icositiesofl egv eins)
 ii
i
)Hypercoagul
ableconditi
ons(e.g.polycyt
haemi a,dehydr
at i
on,nephr
oti
c
sy
ndrome,disseminat
edcancer s)
iv
)Shock
v)Ti
ssuedamagee. g.t
rauma,fr
actures,burns,surgery
vi
)Cert
aindrugs(e.g.anaest
heti
cagent s,oralcontracept
ives).

THROMBOSI S
 Gr ossl y, thrombi maybeofv ari
ousshapes, sizesandcomposi t
iondependi ng
upont hesi t
eofor i
gin.
 Ar terialthr ombi tendt obewhi t
eandmur alwhi lethev enoust hr
ombi arered
andoccl usi ve.
 Redt hrombi ar esof t,redandgel atinouswher easwhi t
et hrombi aref i
rm and
pale.
 Mi xedorl ami nat edt hrombi ar
eal socommonandconsi stofalt
er natewhi t
e
andr edl ayerscal l
edl inesofZahn.
 Li nesofZahnr epr esentpal eplateletandf ibr i
nlayer salternati
ngwi t
hdar ker
redcel l
–r i
chl ay ers.Suchl inesar esi gni
fi
canti nthatt heyar eonlyf oundin
thrombi that formi nflowingbl ood.
Postmor tem Cl ot s
 Gr oss:Gel ati
nous, softandr ubber y.Thesur facei s‘chickenf at’
y ell
ow
cov eringt heunder ly
ingr ed‘currantj el
ly
’
 Rel ati
ont ov esselwal l:Weakl yat tachedt ot hev essel wall
 Shape: Taket heshapeofv essel oritsbif
ur cation
 Mi croscopy:nol inesofZahn

Ar
ter
ialThrombi
 Bl
oodf l
ow:Formedinrapidly-
fl
owingbloodofar ter
iesandhear t
 Si
tes:Commoni naor
ta,coronary,
cerebral
,il
iac,f
emor al
,renalandmesent
eri
c
arteri
es
 Thr ombogenesi
s:For
medf oll
owingendot hel
ialcell
inj
urye.g.i
n
at
her oscl
erosi
s
 Dev el
opment:Usuall
ymur al,
notoccludi
ngt helumencompl et
ely,
may
propagate

VenousThr ombi
 Bl oodf low:Formedi nslow-movingbl oodi nveins
 Si tes:Commoni nsuperfi
cialvar
icosev eins,deeplegv ei
ns,
popl
iteal
,femoral
andi li
acv ei
ns
 Thr ombogenesis:Formedf oll
owingv enousst asise.g.i
nabdominal
oper ati
ons,chi
ld-bi
rt
h
 Dev elopment:Usuallyocclusi
ve,taket hecastoft hevesseli
nwhichformed,
maypr opagateinbothdirecti
ons

CARDI ACTHROMBI
Theyar emor ecommon
 int heatri
al appendages, especiall
yoft her i
ghtatr
ium,
 andonmi t
ral andaorti
cv alvescalledv egetati
onswhichmaybeseeni n
i
nfectiv
eendocar di
ti
sandnon- bacterialthromboti
cendocardi
tis.
 Car diacthrombi aremur al(non-occlusive)asar et
hemur al
thrombi
encounteredi ntheaortainat herosclerosisandinaneury
smal dil
atat
ions.
FateofThr ombus
1.RESOLUTI ON.Thr ombusact ivatest hef i
brinoly t
icsy stem wi thconsequent
rel
easeofpl asminwhi chmaydi ssol vet het hrombuscompl etelyresulti
ngin
resolut
ion.Usually,l
ysisiscompl eteinsmal lvenoust hrombi .
2.ORGANI SATI ON.Ifthet hrombusi snotr emov ed, i
tst artsget ti
ngor ganised.
Phagocy ticcell
s(neut r
ophi l
sandmacr ophages)appearandbegi nt o
phagocy tosef i
bri
nandcel ldebris.Capi ll
ar i
esgr owi ntot het hrombusf rom the
sit
eofi tsat t
achmentandf i
broblastsst ar tinvadi ngthet hrombus.
 Thus, fi
brovasculargr anulat
iont issuei sf ormedwhi chsubsequent lybecomes
denseandl essv ascularandi scov eredov erbyendot helialcell
s.
 Thet hrombusi nthi
swayi sexcl udedf rom t hev ascul arlumenandbecomes
partofv esselwal l
.
 Thenewv ascularchannel sinitmaybeabl et ore-establisht hebloodf low,
call
edr ecanalisati
on.
3.PROPAGATI ON.Thet hrombusmayenl argei nsi zeduet omor eandmor e
depositi
onf r
om theconst i
tuentsoff lowi ngbl ood.
4.THROMBO- EMBOLI SM.Thet hr ombi i
near l
yst ageandi nfectedt hrombi are
quitefr
iableandmaygetdet achedf rom t hev essel wall.

EMBOLISM
 Embolism i
st heprocessofparti
alorcompleteobstruct
ionofsomepartof
thecardi
ovascularsystem byanymasscar r
iedinthecir
culat
ion;
 thetr
ansportedintr
avascularmassdetachedfrom it
ssiteofori
gini
scall
edan
embolus.

Dependingupont hemat teri

ntheembol i:
 Solide.g.detachedt hrombi(thromboembol i)
,at
heromat
ousmater
ial
,tumour
cel
lclumps, t
issuef r
agments, par
asites,bact
eri
alcl
umps,f
orei
gnbodi
es.
 Liquide.g.fatglobules,amnioticfl
uid,bonemarrow.
 Gaseouse. g.ai r
,othergases.

Dependingupont hesourceoft heemboli

:
 Car di
acembol ifr
om l
eftsideofthehearte.g.Embol i
or i
ginat
ingfr
om atr
ium
andatri
alappendages,i
nfarctint
heleftventr
icl
e,vegetationsofendocar
diti
s.
 Ar t
eri
alembolie.g.i
nsystemi car
ter
iesinthebrain,spleen,ki
dney,i
ntest
ine.
 Venousembol ie.
g.i
npulmonar yart
eri
es.

Art
er i
al( sy stemic)t hr omboembol i
sm
 Causeswi t
hinthehear t(80- 85%) :Thesear emur althrombi i
nt heleftatr
ium or
l
eftv ent ricl
e,veget ati
onsont hemi tr
al oraor ticv alves,pr
ost heti
chear tval
ves
andcar diomy opat hy.
 Causeswi t
hinthear teri
es:Thesei ncludeembol idev el
opi
ngi nrel
ationto
atheroscl eroticpl aques, aor t
icaneur y sms, pul monar yvei
nsandpar adoxical
arterial embol if
rom t hesy stemi cv enousci rcul ation.
I
fthev ascul arocclusi onoccur s,thef oll
owi ngill-effectsmayr esult:
 I nfarctionoft heor ganori t
saf fectedpar te.g.I schaemi cnecr osisinthelower
l
imbs( 70-75%) ,spl een,kidney s,brain, i
ntestine.
 My ocar dialinfarct i
onmayoccurf ollowi ngcor onar yembol i
sm.
 Gangr enef oll
owi ngi nfarctionint hel owerl i
mbsi fthecollateralcir
culati
onis
 i
nadequate.
 Art
eri
ti
sandaneury
sm format
ionfr
om bact
eri
alendocar
dit
is.
 Suddendeathmayresul
tfr
om cor
onar
yembolism orembolism i
nthemi
ddl
e
cer
ebralart
ery
.

Venousthr
omboembol ism
Venousembolimayarisef r
om thef
ollowi
ngsources:
 Thrombiinthevei
nsoft helowerlegsaret
hemostcommoncauseofv
enous
embol
i.
 Thrombiinthepel
v i
cv ei
ns.
 Thrombiinthevei
nsoft heupperlimbs.
 Thrombosisincavernoussi
nusoft hebrai
n.
 Thrombiintheri
ghtsideofheart.

Pulmonar yThr omboembol i

sm
Themostsi gni ficantef fectofv enousembol i
sm i sobst ructi
onofpul monar y
arterial ci
rcul ation.Pul monar yembol iaremor ecommoni nhospi tali
sedorbed-
ri
ddenpat ient s.Thecausesar easf ollows:
 Thr ombi or i
gi nat i
ngf rom l argev einsofl owerl egs( suchaspopl i
teal,femor al
andi l
i
ac)ar et hecausei n95%ofpul monar yembol i.
 Lesscommonsour cesi ncludet hrombi inv aricositi
esofsuper fi
cial veinsof
thel egs, andpel vicv einssuchasper i
prostat ic,periov ar
ian,ut erineandbr oad
l
igamentv eins.
 Cl inical f
indi ngs
 Suddendeat h
 Duet oasaddl eembol usoccl udi ngthemaj orpul monar yar t
ery
branches
 Cl inical f
indi ngs
 Corpul monal e+acut er i
ghthear tfailur e
 Suddenoccl usionof>60%ofpul monar yv ascul ature, presentsa
highr i
skacut epul monar yhaemor rhage/ i
nfarction
 I nfar ctushaemor rhagicuspul moni s
 embol usi nt heset ti
ngofl eft-
si dedcar diacfailure( andr esult
ant
sluggishbr onchi alarterybloodf low)
Fatembol ism
 Causes
– Mostof tenduet ot raumat i
cf ractureoft helongbones( e.g.,femur )
– Ot hercausesi ncl udet raumat ofat-l
adent issues, fatt
yl iver .
AirEmbol i
sm
 Gasbubbl eswi thintheci rculat i
oncanobst ructv ascul arflow( andcausedi st
al
i
schemi cinj ury )
 Ai rmayent ert heci rcul ationdur i
ng
– obst etricpr ocedur es
– orasaconsequenceofchestwal li
nj ury .
 bubbl escancoal escet of ormf rothymassessuf ficientlylargeto
occludemaj orv essel s focal necr osis( pulmo, brain).
 mor et han100mLofai rarerequi r
edt opr oduceacl i
nical ef
fect

TumourEmboli
sm
 Mali
gnantt
umourcel
l
sinv
adet
hel
ocal
bloodv
essel
sandmayf
ormt
umour
 emboli
tobelodgedel
sewhere,pr
oducingmet
astat
ictumourdeposi
ts.
 Not
ableexamplesar
eclearcel
lcar
cinomaofki
dney,car
cinomaofthelung,
mal
ignantmelanomaet
c.

I
SCHAEMI A
I
schaemi ai sdef inedasdef icientbloodsuppl ytopar tofati
ssue.Thecessation
ofbloodsuppl ymaybecompl eteorpar ti
al.
Theadv er seef fectsofischaemi amayr esultfr
om 3way s:
 Hy poxi aduet odepr i
vati
onofoxy gent otissues;
 Mal nour ishmentofcel l
sduet oinadequat esuppl yofnutr
ientstotheti
ssue
(i.
e.gl ucose, ami noacids) ;t
hisisl essimpor tant.
 3.I nadequat ecl earanceofmet abol i
tes.
 I nfar ctioni sthepr ocessoft i
ssuenecr osisresult
ingfrom somef or
m of
circul at oryi nsuff i
ciency;
 t hel ocal isedar eaofnecr osissodev elopedi scal
ledaninfarct.
 Gener al ly,sudden, compl ete, andcont inuousoccl usi
on(e.g.thr
ombosisor
embol ism)pr oducesi nfarcts.

TYPESOFI NFARCTS
Accordingt ot hei rcol our :
 Pal eoranaemi c, duet oar teri
alocclusi
onandar eseenincompactor ganse.g.
i
nt heki dney s, hear t,spleen.
 Redorhaemor rhagi c,seeni nsof tl
ooseti
ssuesandar ecausedei therby
pulmonar yar terial obstruction(e.g.i
nthelungs)orbyar t
eri
alorvenous
occlusion( e.g.i nt hei ntestines).
 Gr ossly, i
nfar ctsofsol i
dor gansar eusual
lywedgeshaped, t
heapexpoi nt
ing
towardst heoccl udedar teryandt hewidebaseont hesur
faceoft heorgan.
 Mi croscopi cal ly, thepat hognomoni ccyt
ologicchangeinalli
nfar
ct sis
coagulat i
ve( ischaemi c)necr osisoftheaffect
edar eaoft
issueoror gan.
 Att heper i
pher yofani nfarct,i
nfl
ammat oryreacti
onisnoted.I
niti
ally,
neutrophilspr edomi nat ebutsubsequent l
ymacr ophagesandf i
broblasts
appear.
 Ev entual l
y,thenecr oticar eaisreplacedbyf i
brousscarti
ssue,whichatt i
mes
mayshowdy st rophi ccal cifi
cati
on.

Inf
arctusanemi cusr
enis
Necroti
ct i
ssuei spaleandeosinophi
li
candonl yghost softhenor mal
str
ucturesmaybeseen.Ther ear
enov isibl
enucleiinthenecroti
car ea.
 Thenecr oticareaisdemarcat
edf r
om t hesurroundingvi
talparenchy
ma
byneutrophilsandmor etowardstheuni nvol
vedt i
ssue–rim of
ext
ravasatedEranddi st
endedcapillari
es(hemorr
hagic–hyperaemiczone)
.

MYOCARDI ALI NFARCTI ON

 Indev elopedcount ri
es,acut
eMIaccount sfor10-25%ofalldeaths.
 Theet iologicroleofsev erecor
onaryatheroscl
erosis(morethan75%
compr omi seoflumen)ofoneormor eofthethr
eemaj orcoronaryart
eri
al
trunksint hepat hogenesisofabout90%casesofacut eMI.
 Gr ossl
y ,mosti nfarctsoccursi
nglyandvaryinsizefrom 4to10cm.
 In3- 7day s,theinfarcthashyperaemicborderwhilethecentr
eisy el
l
owand
sof t
.
  Ar
eaofcoagul at
ivenecrosi
s:gr
anul
areosinophil
i
ccytopl
asm of
myocar
dialcel
l
s,indi
sti
nctcrossstr
iat
ions,
nucleioft
hecell
shav e
di
sappi
ered.

CEREBRALI NFARCTI ON
Occlusionoft hecer ebr al arteriesbyei thert hrombi orembol i i
st hemostcommon
causeofcer ebr ali
nfar ction.
 Thr ombot i
coccl usionoft hecerebr al arter
iesismostf requentlyt heresul
tof
at herosclerosis, andr arely,from ar t
eritisoft hecranial ar t
eri
es.
 Embol icarterialoccl usioni scommonl yderivedfrom t hehear t
,mostof t
en
from mur althrombosi scompl i
catingmy ocardiali
nfarct ion,fr
om at ri
al
fibril
lati
onandendocar di ti
s.
 Gr ossly ,
cerebr al anaemi cinfar
ctbecomesev i
dent6- 12hour saf teri
ts
occur r
ence.Theaf f ectedar eaissof tandswol len.
 Lat er,thereiscent ral li
quef acti
onwi thper ipheralfi
rm gl ialreactionand
thickenedl ept omeni nges, formingapseudocy st.
 Looseappear anceoft henecr oti
car eacompar edt ot hev italbr ai
n
par enchy ma.
 Att her im oft heuni nv olvedbr ainonef i
ndsl i
pid-ladenmacr ophages,
hemosi derophagesandr edneur ons.

I
NFARCTLUNG
 Embol ism oft hepul monar yar t
eriesmaypr oducepul monar yinfarcti
on,
thoughnotal way s.Thisi sbecausel ungsreceivebl oodsuppl yf rom bronchi
al
ar teriesaswel l, andt husoccl usionofpul monar yar teryordinar i
l
ydoesnot
pr oducei nfarct s.
 Howev er,i
tmayoccuri npat ientswhohav einadequat eci r
culat i
onsuchasi n
chr oni clungdi seasesandcongest i
veheartfail
ure.
 Gr ossl y ,
pulmonar yinfarctsar ecl assical
lywedge- shapedwi thbaseont he
pleur a, haemor rhagic, variableinsi ze,andmostof teni nthel owerl obes.Cut
sur facei sdar kpur pleandmayshowt heblockedv essel neart heapexoft he
infar ctedar ea.
 Mi cr oscopi cally,thenecr ot i
car eaappear sasr edhaemor rhagiczone,
floodedwi t
hErandhaemosi der ophages.Theunder ly
ingl ungst r
uctureis
indi stinctwi thonl yghost sofal v eol
arsept a,bronchi olesandbl ood
vessel sr emai ni ng.

SHOCK
 I tisreducedper fusionoftissues,causedbyr educedcardi
acoutputorby
reducedef f
ectiveci r
culat
ingbl oodv ol
ume
 I nadequat etissueper fusi
on Cel lul
arhy poxi
a
Car
diogeni cShock
 My ocar di
alinfarcti
on
 Vent ricul
arrupture
 Ar rhy thmia
 Car diactamponade
 Pul monar yembol i
sm
 Fai lureofmy ocardialpumpr esult
ingfrom intr
insi
cmy ocar
dial
damage,
extrinsicpressure, orobstructi
ont oout f
low
Hy
povol
emicShock
 Haemorrhage
 Fl
uidl
oss( e.
g.,
v omit
ing,
diarr
hea,burns,t
rauma)
 Lowcardiacoutputduetoinadequatebloodorpl
asmav
olume

Septi
cShock
 Overwhelmingmicrobiali
nfect
ions
 Gram-negati
vesepsis
 Gram-posit
ivesepti
cemia
 Fungalsepsis
 Superant
igens(e.g.
,toxi
cshocksy ndr
ome)

MORPHOLOGY
 Thecel l
ularandt i
ssueeffect
sofshockar ecausedbyacombi nati
onof
hypoperfusionandmi crovascul
arthrombosis.
 Althoughanyor gancanbeaf f
ected,thebr
ain,hear
t,ki
dney
s,adrenals,
and
gastroi
ntestinaltractaremostcommonl yi
nv ol
ved.
 Fibri
nthrombi canf or
mi nanytissuebuttypi
call
yaremostreadi
lyvisuali
zed
inkidneyglomer ul
i.

Di
ssemi natedI ntrav ascul arCoagul ation( DI C)
 DI Coccur sasacompl i
cat ionofawi dev arietyofdi sorder s;
 causedbyt hesy stemi cact iv ationofcoagul at
ionandr esultsintheformation
oft hrombi t hroughoutt hemi croci rcul ation.
 Asaconsequence, platelet sandcoagul ationf actorsar econsumedand,
secondar i
ly, fi
brinolysisi sact iv ated( t het ermi sconsumpt ivecoagulopathy).
DI
Cusual l
yi st r
igger edbyei ther
(1)ther eleaseoft issuef act orort hr ombopl ast i
csubst ancesi ntothecir
culati
on
– Obst et ri
cCompl icat i
ons
 Abr upti
opl acent ae
 Ret aineddeadf et us
 Sept i
cabor tion
 Amni oticf luidembol i
sm
– Neopl asms
 Car cinomasofpancr eas, pr ostate, l
ung, andst omach
 Acut epr omy elocy ticl eukemi a
(2)wi despr eadendot helial cel l damage
– I nfect i
ons- t
oxemi a
 Sepsi s(gr am- negat iveandgr am- posit
ive)
 Meni ngococcemi a
 Hi stoplasmosi s, Asper gill
osi s,Mal ari
a
– Massi veTi ssueI nj ury
 Tr auma, Bur ns, Ext ensi v esur gery
Morphology
Thebl eedi ngtendencyassoci at edwi thDI Ci smani f
estednotonl ybylar
ger-t
han-
expectedhemor rhagesnearf oci ofi nfar ctionbutal sobydi ff
usepet echiaeand
ecchy mosesont heski n, serosal li
ni ngsoft hebodycav it
ies,epi car
dium,
endocar dium, lungs, andmucosal liningoft heur i
nar ytract .

Cl
ini
cal
Cour
se
  Thepr
ognosisforpatientswithDI Cishighl yvari
able
– dependsont henat ur
eoft heunder lyingdisorderandt hesever
it
yofthe
i
ntr
avascularclott
ingandf ibri
nolysis.
 acut eDIC( e.g.,
obst et
ri
ccompl i
cat
ions)isdomi nat
edbya
bleedi
ngdi athesis
– Apr olongedpost partum bleeding,petechiaeand
ecchy mosesont heski n,severehemor rhageint
othegut
orurinarytract.

I
nfl
ammat
ionandHeal
ing

 I
nf l
ammationist
hebody ’
scomposi t
ecell
ularandv ascularreactiontoinj
ury.
 I
nf l
ammationisaprotect
iveresponseoflocalbloodv essels,bloodcell
s,
plasmaprotei
ns,andcell
sinthet i
ssuesurr
oundi ngtheinjury.
 I
toccursasachai nofeventsdesignedtoli
mi tt
heef fectofinjury,neut
ral
ize
theoff
endingfor
ce,andinit
iatetherepai
rprocess.

CAUSES
 Infect
iveagentslikebacteri
a, v
irusesandt hei
rtoxins,
fungi,
par
asi
tes.
 Immunol ogicalagentsli
kecel l
-mediatedandant i
gen-anti
bodyr
eacti
ons.
 Phy si
calagentslikeheat,cold,r
adiation,mechanicalt
rauma.
 Chemi calagentslikeor
gani candi norgani
cpoisons.
 Inertmateri
alssuchasf oreignbodi es.

SI
GNSOFI NFLAMMATI ON
 Rubor( r
edness);
 Tumor( swelli
ng)
;
 Calor(heat);
 Dolor(pain).
 Functi
ol aesa (lossoff
unct
ion)
Infl
ammat i
onofanorganisusuall
ynamedbyaddingthesuf
fi
x-i
ti
stoi
tsLat
inname
e.g.appendi
cit
is,
hepat
it
is,
cholecy
sti
ti
s,meni
ngi
ti
setc.

TYPESOFI NFLAMMATI ON
 Acut einf
lammat i
oni sofshor tdur ati
on( l
astingl essthan2weeks)and
representst heear lybodyr eact i
on, r
esolvesqui cklyandi susual lyfol
lowedby
healing.
 Themai nfeat uresofacut ei nfl
ammat ionare:
1.accumul at ionoff l
uidandpl asmaatt heaffect edsite;
2.pol y
mor phonucl earneut rophi l
sasi nfl
ammat or ycell
s.
 Chr oni ci
nflammat ionisofl ongerdur at i
onandoccur seitheraf t
erthe
causat i
veagentofacut einflammat i
onper sistsf oralongt i
me, orthest i
mul
us
issucht hati tinduceschr onici nfl
ammat i
onf rom t hebegi nning.
 Thechar acter ist
icfeatureofchr onicinfl
ammat ioni spresenceofchr onic
inf
lammat orycel l
ssuchasl y mphocy tes,plasmacel lsandmacr ophages,
granulati
ont issuef ormation, andi nspecifi
csi tuationsasgr anulomat ous
inf
lammat i
on.
 I nsomei nstances, theterm subacut einfl
ammat i
oni susedf orthestateof
inf
lammat i
onbet weenacut eandchr onic.

ACUTEI NFLAMMATI ON
 Acut einflammat oryr
esponsebythehostt
oanyagenti
saconti
nuous
pr ocessbutfort hepurposeofdi
scussi
on,
itcanbedi
vi
dedi
ntofol
lowi
ngt
wo
ev ents:
I.Vascul arevents.
II.Cell
ularevents.

VASCULAREVENTS
1.Irrespect iveoft het ypeofi njury,immedi at ev ascul arresponsei soft ransient
vasoconst rictionofar ter i
oles.
2.Nextf ollowsper sistentpr ogr essivev asodi latation.Vasodi latationr esultsin
increasedbl oodv olumei nmi crov ascularbedoft hear ea,whi chi sr esponsiblefor
rednessandwar mt hatt hesi teofacut einf lammat ion.
3.Pr ogressi vev asodi l
at ation, inturn,mayel ev atet helocalhy drost aticpressure
resulti
ngi nt r
ansudat i
onoff luidintot heext racellularspace.Thi sisr esponsi bl
e
forswel lingatt helocal si teofacut einf l
ammat i
on.
4.Slowi ngorst asisofmi cr oci r
culati
onf ollowswhi chcausesi ncreased
concent rat i
onofr edcel ls, andt hus,raisedbl oodv iscosity.
5.St asi
sorsl owingi sf ollowedbyl eucocy ticmar ginationorper ipher alorientat
ion
ofleucocy tes( mai nlyneut rophi l
s)alongt hev ascul arendot heli
um.The
leucocy t
esst ickt othev ascul arendot helium br i
efly,andt henmov eandmi grat
e
throught hegapsbet weent heendot helial cellsint otheext ravascul arspace.Thi s
processi sknownasemi gration.

CELLULAREVENTS
 Thecellul
arphaseofinf
lammationconsi
stsof2pr
ocesses:
1.exudati
onofleucocyt
es;and
2.phagocytosi
s.

Whi
tebl
oodcel
ls,
WBCs
 Ther ear et hr eet ypesofl eukocy tes( whi tebl oodcel ls, WBCs) : gr anul ocy tes,
lymphocy tes, andmonocy tes.
 Gr anul ocy teshav ear elativel ysmal l
,mul ti
lobednucl eusandal argeamountof
cytoplasm, whi chcont ainsl ar gegr anul est hatar eact ual l
yl ysosomesf i
lled
withdi gest i
v eenzy mes.Gr anul ocy tescancr awl t hrought issues( diapedesi s)
andswal lowmi crobesandot herpar t
icul atemat ter( phagocy tosi s).Theyar e
themai ncel lsi nacut ei nflammat ionandacut eal ler gi creact ions.
 Gr anul ocy tesconst ituteabout70%ofci rcul atingWBC.
 Thet hr eet y pesar enamedaccor dingt ot hecol ori mpar tedt ot hei rly sosomes
byast andar dl abor ator ydy e:
•Neut rophi lshav eneut r
al (tan)gr anulesandasegment ed, mul t i
lobednucl eus.
Theyar et hemai ni nflammat or ycel l
si nacut ei nf lammat ion.Thei rmai nt aski s
phagocy tosi s.Neut rophi lsal sopr oducechemi cal messengermol ecul est hat
communi cat et onear bycel lsort odi stantor gans.
•Eosi nophi l
sconst i
tut elesst han3%ofci rcul at i
ngWBC.Theyhav eabi lobed
nucleusandr edcy topl asmi cgr anul eswi thant i-par asi tepr oper t
ies.Eosi nophi l
s
arethepr i
nci pal inf lammat orycel lsi npar asi tici nf ect ions, suchasi ntest inal
wormi nf est ation.Theyar eal soat tract edt oal ler gicr eact ions.
•Basophi l
sar enor mal l
yl esst han1%ofci rcul atingWBCs.Dur ingal ler gic
reacti
ons, theyat tractot heri nf lammat orycel ls, incl udi ngl argenumber sof
eosinophi ls.Thei rbl uepur plegr anul escont ainhi stami ne, whi chisr esponsi blefor
thelocal signsofal lergicr eact i
ons: swel ling, itchi ng, vascul arcongest i
on, and
mucuspr oduct i
on.At i
ssuecel l withsi mi larf eat ur esi st hemastcel l
.
 Ly mphocy tesnor mal lymakeupabout25%ofci rcul at i
ngWBCs.Theyhav ea
singlel argenucl eusandscantcy toplasm wi t hnogr anul es.Theyar emadei n
thebonemar rowandmi gr atet ol y mphoi dor gans, wher et heymat ur e.Thet wo
typesofl y mphocy tes, Bcel lsandTcel ls, aret hemai ncel lsoft hei mmune
system andofchr onici nflammat ion.Bcel l
st hatar eact ivelymaki ng
antibodi eshav eadi stinctiv eappear anceandar ecal ledpl asmacel l
s.
 Monocy tesnor mal l
yaccountf orabout5%ofci rcul at i
ngWBCs.Theyar el arge
cell
swi thal ar genucl eusandamodestamountofcy topl asm wi thaf ewsmal l
granul es.Monocy tesar emadei nt hebonemar r owand, af termi gr ati
ngi nt o
ti
ssue, mat urei nt omacr ophages, whi char ev or aci ousphagocy tes.

Chemi calSi
gnalsMedi at
et heInflammat oryProcess
 Injuredcell
sreleasechemi calsignal
sthatwor ktogethert
opr oduce
i
nflammation,reducetheconsequencesoft heinjury,
andr epai
rthedamage.
 Thesechemi calmediatorsaremol eculesthattr
av el
from oneplacetoanot
her
t
oexer tt
heireffect
.

Cel
l-
Der ivedMedi ators
 Medi atorsmaybeder i
vedfrom plasma, leukocy t
es,endotheli
alcell
s,or
injuredcel l
s.Somear esmallmol eculeslikehi st
ami ne,
wher easothersar e
largepr oteins.
 Hist ami neandser ot
oninarev asoactiveami nesstoredinbasophi l
sandmast
cel l
s, whi chcausev asodil
ati
onandi ncreasedper meabil
it
yofcapi ll
arywal l
s.
 Ar achidoni cacid(AA)andi tsderivativesar eaf amilyofcompoundsder i
v ed
from component sofdamagedcel lmembr ane.
 Prost agl andinsareani mportantexampl e.Compoundsi ntheAAf amilycause
vasodi l
at i
onandi ncreasedcapill
aryper meabi lit
y,andmedi atepainandf ever.
  Someant i-
infl
ammat orydrugsexerttheireffectbybl ockingAAact i
vi
ty.
 Cytokinesar eprot ei
nmol eculessecr
etedbycel lsthatactt oenhancei mmune
react
ionsbyat tr
act i
ngleukocy t
es,st
imul ati
ngphagocy tosis,andcausing
vasodilati
on.
 Somecy t
okinespr omotei ncr
eased“stickiness”ofv ascularendot hel
ialcel
l
s,
whichenabl esbloodcel l
st oatt
achtoendot hel
ialcell
sinor dert
oescapef rom
capil
lariesandmi gratei
ntot i
ssues.
 Somemol ecules(chemoki nes)actaschemi calattr
actant st ol
ureWBCs
towardt hedamage, aprocessknownaschemot axis.

Pl
asma-Der ivedMedi ators
 Thecl ot ti
ngsy stem i sasetofaboutadozenpr oteinst hati nter actwi t
hone
anotheri nacompl excascadet ocausebl oodt oclot,
anecessi tyincont rol
of
hemor rhageassoci atedwi t
hi njury .
 Activationoft hecl ottingsy stem al sost i
mul atestheki ninsy stem and
compl ementsy stems, enhanci ngt hei ract ivi
ty.
 Thecompl ementsy stem i sasetofaboutt wodozenpr oteinst hatr eactwit
h
oneanot herinachai nr eacti
oni ni tiat edbyt heimmunesy stem orbyt he
presenceofpr oduct sder ivedf rom mi crobes.
 Thepr oduct sofcompl ementi nt er act ionscausev asodi lation, attractWBCs,
anddi rect lyattackanddest r
oymi cr obes.
 Theki ni nsy st
em i sclosel yrelatedt ot hecl ott
ingsy stem andconsi stsofmor e
thanadozenbl oodpr ot einsthati nt eractt ogener atemol ecul est hatcause
vasodi lationandi ncreasedendot hel ial cellpermeabi l
ity.
 Brady kinin( Greekbr adus=sl ow+ki nesi s=mov ement )i sact ivatedbyt he
coagul ationsy st em.I tact stost rengt henandpr ol
ongt heef fectofot her
mediat or s,andenhancespai n.

Ty
peofExudat i
on
 Theappear anceofescapedpl asmadet er
mi nest hemor phologi
ct y
peof
infl
ammat ionasunder :
 Ser ous, whentheflui
dexudat er esembl esser um ori swaterye.g.bli
ster
format ioninburns.
 Cat arrhal,
whent hesur faceinflammat ionofepi thel i
um pr
oducesi ncr
eased
secr etionofmucouse. g.commoncol d.
 Fibrinous, whenthefibrincontentoft hef l
uidexudat eishighe.g.i
n
pneumococcalandr heumat icper icarditi
s.
 Pur ulentorsuppurativeexudat ei sformat ionofcr eamypusasseeni n
infectionwi t
hpyogeni cbacteriae. g.abscess, acut eappendici
ti
s.
 Haemor r
hagic,
whent her eisv asculardamagee. g.acutehaemor r
hagic
pneumoni aininfl
uenza.

FATEOFACUTEI
NFLAMMATI
ON

1.Resolut
ion.I
tmeanscompl et eret
ur ntonormal ti
ssuef ol
lowi
ngacute
i
nflammat i
on.Thi
soccur swhent issuechangesar eslightandthecellul
ar
changesarerever
sible.
2.Heali
ng.Heali
ngbyf i
br osi
st akespl acewhent hetissuedestr
uctioninacut
e
i
nflammat i
onisext
ensi vesot hatther ei
snot issueregenerat
ion.Butwhen
ti
ssuelossissuper
ficial,i
tisrestoredbyr egenerati
on.
 3.Suppur ati
on.Whent hepyogeni cbacteri
acausi ngacut einfl
ammat ionresul
tin
sev ereti
ssuenecr osis,t
hepr ocessprogr essestosuppur ation.Ini
tial
ly,
ther
e
i
si ntenseneut r
ophil
ici
nfi
ltr
ation.Subsequent ly
,mi xtur
eofneut rophils,
bact eri
a,fragment sofnecroti
ct i
ssue,celldebrisandf i
brincompr i
sepus
whi chiscont ainedinacav i
tytof or
m anabscess.
4.4.Chr onicinflammat i
on.Persisti
ngorr ecurrentacuteinflammat ionmay
progr esstochr onici
nfl
ammat ioninwhicht hepr ocessesofi nf
lammat i
onand
heal i
ngpr oceedsidebysi de.

CHRONI
CINFLAMMATI ON
I
nfl
ammati
onofpr ol
ongeddurati
on(weeks,
months,
years)inwhi
chact
ive
i
nfl
ammati
on,t
issueinj
ury,andheal
ingpr
oceedsi
multaneousl
y.

Chroni
ci nfl
ammat i
onfoll
owi ngacut einf l
ammat ion:
 whent hetissuedestructionisext ensi ve,orthebacteri
asur vi
veandper si
stin
smal lnumber satthesi teofacut ei nflammat ion(inosteomy el
iti
s,pneumonia
ter minatinginlungabscess) ;
 r ecur rentat t
acksofacut ei nf
lammat ion.
Chroni
ci nfl
ammat i
onstarti
ngdenov o
 Whent heinfecti
onwi thor ganismsofl owpat hogeni
cityischronicfr
om the
begi nning; somemi croorganismsar elessi mmedi at
elytoxi
candi nvokealess
intense, longerlast
ing, i
mmuner esponse( theagentofTB, syphil
is,most
par asitesandf ungi;andsomev iruses) .
Autoi
mmunedi sease-al lautoimmunedi seasei schr oni
candcauseschr oni
c
i
nfl
ammat ion( r
heumat oidar t
hriti
s).
Per
sistentexposur etoinj
uriousagent s(chr onicinfl
ammat ioninresponset odail
y
ci
garet
t esmoki ng) .

GENERALFEATURESOFCHRONI
CINFLAMMATI
ON

1.MONONUCLEARCELLI NFI LTRATI ON.Chr onici

nflammat orylesi
onsar e
i
nfi
lt
rat
edbymononucl earinflammat orycellsli
kephagocy tesandl ymphoidcells.
 Phagocy t
esarerepresentedbyci rcul
atingmonocy tes,t
issuemacr ophages
(t
hebloodmonocy t
esonr eachingtheextravascul
arspacet ransfor
mi nto
ti
ssuemacrophages),epit
helioi
dcel l
sandsomet i
mes, multi
nucleatedgiant
cel
ls.

Epi
thel
ioi
dcel ls
 Thesear esocalledbecauseoft hei
repithel
ialcell
-l
ikeappearance,are
modi fiedmacr ophages.
 I ntheusual HE–stainedti
ssuesecti
ons, theepithel
ioi
dcellshaveapal epi
nk
cyt
opl asm wi t
hindisti
nctcell
boundar i
es,oftenappearingtomer geint
oone
anot her.
 Thenucl eusisovalorelongate.
 Epit helioidcel
lsareweaklyphagocytic.

Mul
ti
nucl
eategiantcel
ls
 Multi
nucl
eategiantcel
l
sar efor
medbyfusionofadj
acentepit
hel
i
oidcel
l
sand
mayhav e20ormor enuclei
.
 Thesenucleimaybearrangedattheper
ipher
yli
kehorseshoeorr
ing,
orare
 clust
eredatt het wopol es( Langhans’ gi
antcel
ls) ,
ort heymaybepr esent
central
ly(foreignbodygi antcel l
s).Thef or
merar ecommonl yseenin
tubercul
osi swhilethelatterar ecommoni nforeignbodyt issuereactions.
 Likeepitheli
oidcells,
thesegi antcell
sar eweaklyphagocy ticbutproduce
secretoryproductswhi chhel pi nremov i
ngtheinv adingagent s.
 Otherchr onicinfl
ammat orycellsincludely
mphocy tesandpl asmacel ls.
 Inchronicinflammat i
on, lymphocy t
esandmacr ophagesi nfl
uenceeachot her
andr el
easemedi ator
sofi nf l
ammat i
on.

2.TISSUEDESTRUCTI ONORNECROSI S.Tissuedest

ructionandnecrosisare
centralf
eaturesofmostformsofchr
onicinflammatorylesions.Thi
sisbrought
aboutbyact i
vatedmacrophageswhi
chr el
easeav ar
iet
yofbi ologi
cal
lyacti
ve
substances.

3.PROLIFERATI
VECHANGES.Asar esul
tofnecrosi
s,pr
oli
fer
ationofsmallbl
ood
vessel
sandfibr
oblast
sisst
imulat
edresul
tinginfor
mati
onofinf l
ammatory
granul
ati
onti
ssue.Event
ual
ly
,heal
ingbyfibrosi
sandcol
lagenlayingt
akesplace.

TYPESOFCHRONI CI NFLAMMATI ON
1.Chr
onicnon- specif
ici
nf l
ammat i
on.Iti
scharact
eri
sedbynon- speci
fi
c
i
nflammator
ycellinfil
tr
atione.
g.chr onicosteomyeli
ti
s,l
ungabscess.
2.Chr
onicgr anulomatousinflammat i
on.Iti
scharact
eri
sedbyf ormati
onof
granul
omase.g.tuberculosi
s,leprosy,syphi
li
s,act
inomycosi
s,sar
coidosisetc.

GRANULOMATOUSI NFLAMMATI ON
 Granul
omaisdefinedasacir
cumscr i
bed,ti
nylesi
on,about1mm i ndiameter
,
composedpredominantl
yofcoll
ecti
onofmodi fi
edmacr ophagescal
led
epit
hel
ioi
dcell
s,andrimmedattheperipherybylymphoi
dcel l
s.
 Formati
onofgranulomaisatypeIVgranulomatoushypersensi
ti
vi
tyreact
ion.

Tuberculousgr anuloma( tuber cl

e)
 Et i
ology :Mycobact er i
um t uber culosis.
 Mor phol ogy:Gr ossly ,tuber clesv arywi dely
,fr
om inv isi
blewit
hnakedey e,
smal lmi ll
et-
likef ocuses( 1- 2mm) ; ornodul esexceedi ng2mm.
 Themi li
arylesionsar ey el
lowi sh, fi
rm ar easwithoutgr osslyvi
sibl
ecaseous
necrosi s.
Hist
ology .Cl assicallytuber cleischar acterizedbyt hepr esenceof :
1.Cent r
al caseousnecr osi s
2.Epitheloidcel ls(surroundi ngnecr osis,ar rangedpalisade–l i
ke)
3.Giantcel lsLanghans-t y pe
4.Rim ofl ympocy t
esont heper ipher yoft uber cl
e.
5.Peripher alzoneoff ibrobl astict issuemer gingwithsur roundingstr
uctur
esand
i
ncreasingi namountwi tht heageoft hel esion.

HEALI
NG
 Heal i
ngisthebodyr esponset oinj
uryinanattempttor estorenormal
structur
eandf uncti
on.Heal i
nginvolves2dist
inctprocesses:
 Regener at
ionbyprolif
erat
ionofpar enchymalcell
s;usuallyresul
tsincompl
ete
restorat
ionoftheoriginal
tissues.
 Repairbypr ol
ifer
ati
onofconnect i
vet i
ssueel
ement sresulti
nginfibr
osi
sand
 scar
ri
ng.
 Atti
mes,bot
hthepr
ocessest
akepl
acesi
mul
taneousl
y.

REGENERATI ON
 Somepar enchy malcel
lsareshor t
-l
ivedwhi l
eothershaveal ongerlif
espan.
 I nor dert omai ntai
nproperstr
uctureoft issues,thesecellsareundert he
const antregulat
orycontr
oloftheircellcy cle.
 Cel lcy cl
eisdef i
nedastheper i
odbet weent wosuccessiv ecelldiv
isi
onsandis
dividedi nto4unequal phases:
 M( mi tosi
s)phase:Phaseofmi t
osis.
 G1( gap1)phase:Thedaught ercellentersG1phaseaf termi t
osis.
 S( sy nthesis)phase:Duri
ngthisphase, thesy nthesi
sofnucl earDNAt akes
place.
 G2( gap2)phase:Af t
ercompletionofnucl earDNAduplication,thecellent
ers
G2phase.
 G0( gap0)phase:Thi sistherestingphaseoft hecellafteranM phase.

Dependingupont heircapacitytodivi
de,thecel
lsofthebodycanbedi v
idedi
nto3
groups:
1.Labil
ecells.Thesecellscontinuetomulti
plyt
hroughoutlif
eundernormal
physiol
ogiccondit
ions.Thesei nclude:
 sur f
aceepithelial
cell
soft heepidermis,
ali
mentarytract
,respi
rator
ytr
act,
uri
narytr
act,vagina,cervi
x,uter
ineendometri
um,
 haemat opoieticcell
sofbonemar rowandcellsofly
mphnodesandspl een.

2.Stablecell
s.Thesecellsdecreaseorlosetheirabili
tytoprol
if
erateafter
adolescencebutr etai
nthecapacit
yt omulti
plyinresponset osti
mulithroughout
adultli
fe.Theseinclude:
 par enchymal cell
soforgansli
keliver,
pancreas,kidneys,adr
enalandt hyroi
d;
 mesenchy mal cell
sli
kesmoot hmuscl ecel
ls,f
ibroblasts,
vascul
ar
endotheli
um, boneandcar t
il
agecells.

3.Permanentcells.Thesecel
l
slosetheirabi
l
ityt
opr
oli
fer
atear
oundt
het
ime
ofbirt
h.Theseincl
ude:
 neur onsofnervoussy st
em,
 skeletalmuscleandcar di
acmusclecel
ls.

 Thei mpor tanceofr egenerati

onintherepl
acementofi njur
edt i
ssuesv ari
esin
diff
erentt ypesoftissuesandwi ththeseveri
tyofinjury.
 Inepitheli
aoft heint est
inaltr
actandskin,
inj
uredcel l
sarerapidl
yreplacedby
proli
ferati
onofr esidual cel
lsanddiff
erent
iat
ionofcel l
sderiv
edf r
om tissue
stem cel l
s.
 Tissuer egenerati
oncanoccuri nparenchymalorganswhosecel l
sarecapable
ofproliferati
on,butwi ththeexcepti
onoftheliv
er,thisisusuall
yalimited
process.

REPAIR
 Ifrepaircannotbeaccompli
shedbyregener
ati
onalone,itoccur
sby
replacementoft hei
njur
edcell
swit
hconnecti
vetissue,l
eadingtot
he
format i
onofascar ,
orbyacombinati
onofregenerati
onofsomer esi
dual
cel
l
s
 andscarf ormation.
 Scarri
ngmayhappeni fthetissueinj
uryissev er
eorchr onicandresul
tsin
damaget oparenchymal cell
sandepi thel
iaaswel lastot heconnecti
veti
ssue
framewor k,
orifnondiv i
dingcellsareinj
ured.
 Incontrasttoregenerati
on, whichinvolv
esther esti
tut
ionoft i
ssue
component s,scarformat i
oni saresponset hat“pat
ches”r at
herthanrest
ores
theti
ssue.
 Twopr ocessesar einvolvedinrepair:
1.Granulati
ont i
ssueformat i
on; and
2.Contracti
onofwounds.

Repairr
esponsetakesplacebypar t
icipat
ionofmesenchy malcell
s( consi
sti
ngof
connect
iveti
ssuestem cell
s,fi
brocytesandhisti
ocyt
es),endothel
ialcell
s,
macrophages,pl
atel
ets,andtheparenchy malcel
lsoftheinj
uredor gan.

Contr
actionofWounds
 Thewoundst ar
tscont
racti
ngaf t
er2-3day
sandt heprocessiscomplet
edby
the14t hday.
 Dur i
ngthisperi
od,t
hewoundi sr
educedbyapproxi
mat el
y80%ofi t
sori
ginal
size.
 Cont r
actedwoundresult
sinr api
dheali
ngsincel
essersurfacear
eaofthe
injur
edt i
ssuehastobereplaced.

WOUNDHEALI NG
 Heal
ingofskinwoundspr ovi
desacl assi
calexampleofcombi
nat
ionof
r
egenerat
ionandr epairdescri
bedabov e.
 Woundhealingcanbeaccompl ishedinoneoft hef
oll
owingt
woway s:
 Heal
ingbyfirsti
ntent
ion( pr
imaryunion).
 Heal
ingbysecondi ntenton(
i secondaryunion).

Heal
ingbyFi r
stIntent
ion(Pri
maryUnion)
 Thisisdefinedasheali
ngofawoundwhi chhasthefol
lowi
ngchar
act
eri
sti
cs:
 cl
eananduni nf
ected;
 surgical
l
yincised;
 withoutmuchl ossofcell
sandtissue;
and
 edgesofwoundar eapproxi
matedbysurgi
calsut
ures.

 Thesequenceofev ent sinpr imar yunion:

1.Init
ialhaemor rhage.Immedi atelyafterinj
ury ,
thespacebet weent he
approximat edsur f
acesofi ncisedwoundi sfil
ledwi thbloodwhichthencl otsand
sealsthewoundagai nstdehy dr ationandi nfection.
2.Acut einfl
ammat or
yr esponse.Thi soccur swi thi
n24hour swithappear anceof
polymor phsf rom themar gi
nsofi ncision.
 By3r dday , polymorphsar er eplacedbymacr ophagesandf ibr
oblastsinvade
thewoundar ea.
 By5t hday , newcol l
agenf ibril
sst artformingwhi chdomi nateti
llheal
ingis
compl eted.
3.Epitheli
al changes.Thebasal cel l
sofepi dermi sfrom bot
hthecutmar ginsstar
t
proli
ferati
ngandmi grati
ngt owar dsi ncisi
onal space.
 Awel l
appr oximat edwoundi scov eredbyal ayerofepit
heli
um in48hour s.
 Thebasalcel
l
sfrom t
hemar
ginsconti
nuetodiv
ide.By5thday,amul
ti
layer
ed
newepidermi
sisfor
medwhi
chisdiff
erent
iat
edintosuper
fi
cial
anddeeper
l
ayer
s.

Heal
ingbySecondI ntention(Secondar yUnion)
 Thisisdef inedasheal ingofawoundhav ingt hefoll
owingchar act
eri
sti
cs:
 openwi thal arget i
ssuedef ect,atti
mesi nfected;
 havingext ensivelossofcel lsandt i
ssues;
 andt hewoundi snotappr oxi
mat edbysur gicalsuturesbutisleftopen.
 Thebasi cev entsinsecondar yunionaresimi l
artopr imaryunionbutdif
feri
n
havingal argertissuedef ectwhi chhastobebr i
dged.
 Theheal i
ngbysecondi nt
entionisslowandr esul
tsinal arge,atti
mesugly,
scarascompar edtor apidhealingandneatscarofpr i
mar yunion.
 Speciali
sedst ructuresoft heskinl i
kehairfoll
icl
esandsweatgl andsarenot
repl
aced.

Woundcont r
acti
on.
 Contr
act i
onofwoundisani mport
antf eat
ureofsecondar yheal
ing,notseeni
n
pri
mar yheal
ing.
 Duetot heacti
onofmy of
ibr
oblast
spr esentingranul
ationti
ssue,thewound
contr
actstoone-thi
rdt
oonef ourt
hofi tsori
ginalsi
ze.Woundcont ract
ion
occursatatimewhenact i
vegranulat
iontissueisbeingformed.

Fr
actur eHealing
 Pr i
mar yunionoff ract
uresoccursinafewspecialsit
uati
onswhent heendsof
fractureareappr oximatedasisdonebyapplicat
ionofcompr essionclamps.
 Int hesecases, bonyuniontakesplacewit
hformationofmedul larycal
lus
wi thoutperiostealcal
l
usf or
mation.
 Secondar yuni onisthemor ecommonpr ocessoffractur
ehealing.Thoughi ti
s
acont i
nuouspr ocess,secondar
yboneunionisdescr i
bedundert hefol
lowing
3headi ngs:
 Pr ocall
usf ormation
 Osseouscal lusformati
on
 Remodel l
ing

PROCALLUSFORMATI ON.
1.Haemat oma
2.Localinfl
ammat oryresponse
3.Ingrowthofgranulat
iontissuebeginswithneov ascul
ari
sat
ionand
prolif
erat
ionofmesenchy mal cell
sf r
om per
iosteum andendosteum.Asof t
ti
ssuecal l
usisthusformedwhi chjoi
nstheendsoff ractur
edbonewithoutmuch
strength.
4.Call
uscomposedofwov enboneandcar t
ilagestart
swithi
nthefi
rstf
ew
day s.

OSSEOUSCALLUSFORMATI ON.Theprocal
l
usactsasscaf
fol
dingonwhi
ch
osseouscal
l
uscomposedofl
amell
arboneisfor
med.

REMODELLING.Duri
ngthefor
mat
ionoflamel
l
arbone,osteobl
ast
icl
ayi
ngand
ost
eocl
ast
icremovalar
etaki
ngpl
aceremodel
li
ngtheunit
edboneends,whi
ch
af
tersomet
ime,
isi
ndi
sti
ngui
shabl
efr
om nor
mal
bone

Heal
ingofNervousTi
ssue
CENTRALNERVOUSSYSTEM.
 Thenervecell
soft
hebrain,
spinal
cordandgangl
i
aoncedestr
oyedarenot
repl
aced.
 Thedamagedneurogli
alcel
ls,
however,
mayshowprol
if
erat
ionofast
rocyt
es
call
edgli
osi
s.

PERIPHERALNERVOUSSYSTEM.
 Incontrasttothecel l
sofCNS, theper ipheralnervesshowr egener at
ion,
mai nl
yfrom proli
ferati
onofSchwanncel l
sandf ibril
sf r
om distalend.
 Br i
efl
y,i
tconsistsoft hef ol
lowi ng:
 My eli
nsheathandaxonoft hei ntactdistalnerveunder godegener at
ionupto
thenextnodeofRanv iertowar dst hepr oxi
mal end.
 Degener at
eddebr isarecl earedawaybymacr ophages.
 Regener at
ioninthef orm ofspr outingoff i
bri
lstakespl acefrom t hev i
abl
eend
ofax on.Thesefibril
sgr owal ongt hetrackofdegener atednervesot hati
n
about6- 7weeks, t
heper i
pher al st
umpconsi stsoft ubef i
l
ledwi t
hel ongated
Schwanncel ls.
 Oneoft hef i
bri
lsfrom t hepr oximal stumpent erst heoldneur altubeand
dev el
opsintonewf unctional axon.

ADAPTATIONSOFCELLULARGROWTHANDDI FFERENTIATI
ON
 Adaptat
ionsarerev
ersi
blechangesinthenumber,si
ze,
phenot
ype,metabol
i
c
act
ivi
ty,
orfuncti
onsofcell
sinresponsetochangesint
hei
renvi
ronment.
 Physiologi cadapt ationsusual l
yr epresentr esponsesofcel lstonor mal
sti
mul at i
onbyhor monesorendogenouschemi calmedi ators( e.
g.,the
hormone- i
nducedenl argementoft hebr eastandut erusdur i
ngpr egnancy ),
or
tothedemandsofmechani cal stress( i
nt hecaseofbonesandmuscl es).
 Pathologi cadapt ationsar er esponsest ost ressthatal l
owcel l
st omodul ate
thei
rst ructureandf unct i
onandt husescapei njury
, butatt heexpenseof
normal function, suchassquamousmet aplasiaofbr onchial epitheli
um in
smoker s.
 Decreasi ngori ncreasi ngt heirsizei e.at
. rophyandhy pert
rophyr especti
vely,or
byincreasi ngt hei rnumber-hy per plasia(post fi
xwor d- t
rophymeans
nourishment ;-plasiameansgr owt hofnewcel l
s).
 Changi ngt hepat hwayofphenot y pi
cdi fferent i
ati
onofcel lsi.e.met aplasiaand
dysplasi a(prefixwor dmet a-meanst ransf ormat i
on; dys-meansbad
development ).
 Ingener al,theadapt i
v eresponsesar erev ersibleonwi t
hdrawalofst imulus.
 Howev er,ifthei rri
tantst imulusper sistsf orlongt i
me, t
hecel lmaynotbeabl e
tosur vi
v eandmayei therdieorpr ogressf urthere.g.celldeat hmayoccuri n
sustainedat r
ophy ;dy splasiamaypr ogressi ntocarcinomai nsi t
u.

HYPERTROPHY
 Hy per trophyi sani ncreasei nt hesi zeofcel lsresul t
ingi nani ncreaseinthe
sizeoft heor gan.
 Inpur ehy pertrophyt herear enonewcel ls,justbi ggercel l
scontaini
ng
incr easedamount sofst ructur al prot
einsandor ganel les.
 Hy per plasiaisanadapt i
v eresponsei ncellscapabl eofr epli
cati
on,whereas
hy per t
rophyoccur swhencel lshav eal imitedcapaci tyt odivide.
 Hy per trophyandhy perplasiaal socanoccurt oget her,andobv i
ouslyboth
resul tinanenl argedor gan.
Physi
ol ogichy per t
rophy
 Hy per trophymaybephy siologi corpat hologic.Inbot hcases, i
tiscaused
eitherbyi ncreasedf unctional demandorbyhor monal stimulati
on.
 Enl argedsi zeoft heut erusi npr egnancyisanexcel lentexampl eofphysiol
ogi
c
hy per t
rophyaswel l
ashy per plasia.
 Incont rast,inresponset oi ncr easedwor kloadt hest r
iatedmuscl ecel
lsin
bot ht heskel etalmuscl eandt hehear tunder goonl yhy per t
rophybecause
adul tmuscl ecellshav eal imi t
edcapaci tytodi vide.
 Ther efore,thephy si
queoft hewei ghtl
ift
erst emssol elyf rom thehypertr
ophy
ofi ndiv i
dual skeletal muscl es.

Pat
hologichyper t
rophy
 Hy pert
rophyofcar diacmusclemayoccurinanumberofcardi
ovascular
diseases.
 Af ewcondi t
ionspr oducingl
eftv
entr
icul
arhyper
trophyar
easunder:
 Systemichy pertension
 Aor t
icvalv
edi sease( st
enosi
sandinsuff
ici
ency)
 Mi t
rali
nsuffi
ciency

 Ahy per
trophiedheartofapatientwit
hsy st
emichy per
tensionmayweigh700-
800gascompar edt
oav eragenormal adul
tweightof350g.
 Grossly
,thicknessoftheleftv
entri
cularwall(
excl
udingtrabecul
aecar
neae
 andpapi
ll
arymuscles)above15mm isindicati
veofsigni
fi
canthypert
rophy
.
Thepapi
ll
arymusclesandt r
abecul
aecarneaeareroundedandenlarged.
 Micr
oscopi
cal
ly
,thereisincr
easeinsi
zeofi ndi
vi
dualmusclefi
bres.

CORPULMONALE:i
ncreasei
nthi
cknessoft
her
ightv
ent
ri
cul
arwal
lfr
om i
ts
nor
mal3t
o5mm upt o10mm ormor e.

 Elect ronmi cr oscopyr evealsi ncr easei nt henumberofmy of i

lament s
compr i
singmy ofibrils,mi t
ochondr ial changesandmul tipleinter calat eddiscs
whi char eact i
v esi tesf orthef ormat i
onofnewsar comer es.
 Besi des, thenucl eicaci dcont entdet ermi nationshav eshowni ncr easei nt ot
al
RNAandi ncreasedr at i
oofRNAt oDNAcont entoft hehy per trophi ed
my ocar dial f
ibr es.
 My ocar dium subj ectedt oaper sist ent l
yincr easedwor kload( hy per tensi onor
stenot i
cv al
v e), adapt sbyunder goi nghy per t
rophyt ogener atet her equired
highercont ract ilefor ce.
 If
, ont heot herhand, themy ocar dium i ssubj ect
edt or educedbl oodf low
(i
schemi a)duet oanoccl udedcor onar yar tery,t
hemuscl ecel lsmayunder go
i
njur y.
 Anadapt ati
ont ost resssuchashy per t
rophycanpr ogresst of unct ionally
si
gni ficantcel linjuryi fthest ressi snotr elieved.
 Whent hishappensi nt hehear t,sev eraldegener ati
vechangesoccuri nt he
my ocar dial f
iber s: fragment ationandl ossofmy ofi
br i
ll
arcont ractileel ements.
 Whyhy per t
rophypr ogr essest ot heser egr essivechanges: theremaybef i
nit
e
l
imi tsont heabi li
tiesoft hev ascul at uretoadequat elysuppl yt heenl arged
fi
ber s, t
hemi tochondr iatosuppl yATP, ort hebiosy ntheticmachi ner yt o
prov idesuf fi
ci entcont r
actil
epr ot einsorot hercy t
oskel etalelement s.

LEFTVENTRI CULARDI LATI

ON
Thenetresul
tofthesedegenerat
ivechangesisventr
icul
ardi l
ati
onandult
imatel
y
car
diacfai
lur
e.
 Anincreaseinthenumberofcell
si nanorganortissue,usual
l
yresul
ti
ngin
incr
easedmassoft heorganortissue.
 Takesplaceift
hecellpopul
ati
oni scapabl
eofdi v
iding.

HYPERPLASI
A
 Anincreasei
nthenumberofcell
sinanorganort
issue,usual
l
yresul
ti
ngi
n
i
ncr
easedmassoftheorganorti
ssue.
 Takesplacei
fthecel
lpopul
ati
oniscapabl
eofdiv
iding.

Phy
siol
ogichormonal hyper
plasia
 Theprolif
erat
ionoft heglandularepit
hel
ium ofthef
emalebreastatpuber
ty
andduringpregnancyandl act
ation.
 Prol
if
erati
veact i
vit
yofnor mal endometr
ium aft
ernormalmenstrual
cycl
e.
 Prost
atichyperplasiainoldage.

 Physi
ologi
ccompensat oryhyperpl
asi
a:hy perpl
asi
aoccur
ringf
oll
owing
removalofpartofanorganoracont r
alateralor
ganinpai
redorgan.
 Regenerat
ionoftheli
verfol
lowingpart
ialhepatect
omy.
 Regenerat
ionofepider
misaf t
erskinabrasion.
 Foll
owingnephr
ect
omyononesi
de,t
her
eishyperpl
asiaofnephr
onsoft
he
otherki
dney.
 Adrenalhy
perpl
asi
afol
l
owi
ngremov
alofoneadrenalgl
and.

Pathologi chy perplasia:duet oexcessi vestimul ationofhor monesorgr owt h

fact
or s.
 Endomet rialhyper plasiafollowi ngoest r
ogenexcess.
 I nwoundheal ing,ther eisf ormat i
onofgr anulat iontissueduet opr oliferat
ion
off ibrobl
ast sandendot helialcel l
s.
 For mat i
onofski nwar t
sf rom hy perplasiaofepi der misduet ohuman
papi ll
omav ir
us.
 I ntraductal epitheli
al hyperpl asiai nthebr easti nf i
br ocysticbreastdi sease.
 Ani mpor tantpoi nti sthati nal loft hesesi tuations, thehy perpl
ast i
cpr ocess
remai nscont r
ol l
ed; i
fthesi gnal st hatinit
iat eitabat e, t
hehy perplasia
disappear s.
 I tdistinguishespat hologichy perplasiasf rom cancer ,
inwhi chthegr owt h
cont rolmechani smsbecomeper manent lydy sr egulatedori neffective.
Nev ertheless, i
nmanycases, pat hologichy perpl asiaconst it
utesaf ertil
esoili
n
whi chcancer smayev entual l
yar ise.Forexampl e,patientswithhy per plasiaof
theendomet ri
um ar eatincr easedr iskofdev elopingendomet ri
al cancer .

ATROPHY
 Reduct i
onofthenumberandsi zeofpar
enchymalcel
l
sofanorganori
tspar
ts
whi chwasoncenormal i
scalledatr
ophy.
 Hy poplasi
aisthet
erm usedfordevel
opmental
lysmal
lsi
ze,and
 aplasiaforext
remefai
lureofdevel
opmentsothatonl
yrudi
mentar
yti
ssuei
s
present.

Physi
ologi
catr
ophy.Atr
ophyi sanormalpr
ocessofagi
nginsomet issues,
whi
ch
coul
dbeduet olossofendocrinest
imul
ati
onorart
eri
oscl
erosis.
 Atrophyofl
ymphoidtissueinlymphnodes,
appendi
xandt hymus.
 Atrophyofgonadsaftermenopause.
 Atrophyofbrai
nwithaging.

Pat
hologi catrophy
 Starvationat r
ophy :therei sfir
stdepl etionofcar bohydrateandf atstores
foll
owedbypr oteincat abolism.
 Ischaemi cat r
ophy .Gradual diminut i
onofbl oodsupplyduet oat her
osclerosi
s
mayr esultinshr i
nkageoft heaf fectedor gane. g.
 Smal latrophicki dneyinat heroscl erosisofr enalart
ery.
 Atrophyofbr ainincer ebral at
heroscl erosis.
 Disuseat rophy .Prolongeddi minishedf uncti
onalacti
vityisassociatedwith
disuseat rophyoft heor gane. g.wast ingofmuscl esoflimbimmobi l
isedin
cast.
 Neur opathicat rophy.Interruptioni nner vesupplyleadst owastingofmuscl es
e.g.
 Poliomy eli
tis
 Mot orneur ondi sease
 Nerv esect i
on.
 Endocr ineat r
ophy .Lossofendocr iner egulator
ymechani sm r
esultsin
 reducedmet aboli
cact i
vi
tyofti
ssuesandhenceat r
ophye.g.
 Hy popituit
arism mayleadtoatrophyofthyroid,
adrenalandgonads.
 Hy pothy r
oidi
sm maycauseat rophyoftheski nanditsadnexalstr
uctur
es.
 Pressur eatrophy.Prol
ongedpressurefrom benigntumoursorcy stor
aneur ysm maycausecompr essionandatrophyoft heti
ssuese.g.
 Erosionofskul lorbrainbymeningiomaarisingfrom pi
aarachnoid.
 Idi
opat hicatrophy.Therear
esomeexampl esofat r
ophywher enoobv i
ous
causei spr esente.g.
 My opat hi
es.
 Testicularatrophy.

METAPLASI A
 Met apl asi aisar eversiblechangei nwhi chonedi ff
er ent iatedcel l type
(epithel ialormesenchy mal )isreplacedbyanot hercel lty pe.
 Met apl asi adoesnotr esul tfr
om achangei nt hephenot ypeofanal ready
different iatedcel ltype; insteadi tist her esul tofar epr ogr ammi ngofst em
cellst hatar eknownt oexi stinnor mal ti
ssues, orofundi fferentiated
mesenchy mal cell
spr esenti nconnect i
vet issue.
 Themostcommonepi thelialmet apl asi aiscol umnart osquamous, asoccur s
i
nt her espi rat orytracti nr esponset ochr oni ci r
r i
tation.I nt hehabi tual
cigar ettesmoker ,thenor mal cil
iatedcol umnarepi thel i
al cell
soft het rachea
andbr onchi areof tenr eplacedbyst r atifi
edsquamousepi t
helial cells.
 thei nfluencest hatpredi sposet omet aplasia, ifper sistent ,mayi ni t
iate
mal ignantt ransf ormat ioni nmet apl ast icepi thel i
um.
 Thus, acommonf orm ofcanceri nt her espi ratoryt racti scomposedof
squamouscel ls,whichar iseinar easofmet apl asiaoft henor mal col umnar
epithel ium i ntosquamousepi t
helium.
 Met apl asi af rom squamoust ocol umnart ypemayal sooccur ,asi nBar ret
t
esophagus, inwhi cht heesophageal squamousepi thel i
um i srepl acedby
i
nt est i
nal -l
ikecol umnarcel l
sundert hei nfluenceofr efluxedgast ricaci d.
 Connect ivet issuemet aplasiaist hef ormat i
onofcar ti
lage, bone, oradi pose
ti
ssue( mesenchy mal tissues)i nt i
ssuest hatnor mal lydonotcont ainthese
element s.
 Forexampl e, bonef or mat ioninmuscl e,desi gnat edmy ositisossi ficans,
occasi onal l
yoccur saf terintramuscul arhemor rhage.

DYSPLASI A
 Dysplasi ameans‘ disor deredcellulardev el
opment’,oft
enaccompani edwit
h
met aplasiaandhy per plasia;i
tisther efor
ealsor ef
erredtoasat ypi
cal
hyperplasia.
 Dysplasi aoccur
smostof teninepit hel
ialcel
ls.Epi
theli
aldysplasi
ais
charact eri
sedbycel lularpr ol
if
erationandcy t
ologi
cchanges.
 Thesechangesi nclude:
1.Increasednumberofl ayersofepi theli
alcell
s
2.Disor derl
yarr
angementofcel l
sf rom basal l
ayertothesurfacelayer
3.Lossofbasal polar i
tyi .
e.nucleilyingawayf rom basementmembr ane
4.Cellularandnucl earpl eomor phism
5.Increasednucl eocy toplasmicr atio
6.Nucl earhyperchromat ism
7.Increasedmi t
ot i
cact ivi
ty.
Ri
skfactorsf ordy splasi a
– Hy perplasi a
– Met aplasi a
– I nf
ect i
on
 humanpapi ll
omav i
rusty pe16, causi
ngsquamousdy splasi
aof
thecer v i
x
– Chemi cal s
 irr i
tantsinci gar
ettesmoke, causingsquamousmet apl
asiato
pr ogresst osquamousdy splasi
aandcar cinoma
– Ul travi
ol etlight
 sol ardamageoft heski n,causingsquamousdy spl
asia
 Onr emov aloft hei nciti
ngst i
mulus, t
hechangesmaydi sappear .
 Inapr oporti
onofcases, however,dysplasiaprogressesi ntocar nomai
ci nsit
u
(cancerconf i
nedt ol ayerssuperfi
cialtobasementmembr ane)orinvasi
ve
cancer.

TUMOURPATHOLOGY
Neopl
asma/Tumour
 ‘amassoftissuefor
medasar esul
tofabnormal,excessi
ve,uncoordi
nated,
autonomousandpur posel
essproli
ferat
ionofcel
l
sev enaftercessati
onof
sti
mulusforgrowthwhichcausedi t’
 Oncologyi
st hest
udyofneoplasms.

Tumourcomponent s
 Parenchyma’comprisedbyprol
i
ferat
ingtumourcell
s;
 parenchymadeterminesthenat
ureandev ol
uti
onofthetumour.
 ‘Support
ivest
roma’composedoffibrousconnect
iveti
ssueandbloodvessel
s;
 itprovi
desthefr
amewor konwhichtheparenchymaltumourcel
l
sgr ow.

Tumournomencl atur
e
 Thetumour sderiv
et heirnomencl atureont hebasi softhepar enchy mal
componentcompr i
singt hem.
 Thesuffix‘
-oma’i saddedt odenot ebeni gnt umour s.
 Mali
gnantt umourofepi thel
ialori
ginar ecal edcar
l ci
nomas,
 Mali
gnantmesenchy mal tumour sarenamedsar comas( sar cos=f l
eshy)
.
 Foreverybenigntumor ,thereisamat chingmal ignantvariety.Forexampl e,
a
beni
gnt umorofagl andi susuallycalledanadenoma( Greekaden=
gl
and;oma=swel l
ing) ,
whi leabeni gnt umoroff i
brousti
ssuei saf ibr
oma.
 Amal i
gnanttumorofgl andepi theli
al cell
sisanadenocar cinoma, anda
mali
gnantt umoroff ibroust i
ssuei saf ibrosarcoma.
 Somenamesdonotf ollowconv ent i
onsoneat ly:l
ymphomai smal ignant
neopl
asm ofl ymphocy tes.Simi l
arly,amel anomai samal i
gnantt umorof
melanocytes,t
hepi gmentpr oducingcel lsinskin.
l
Thecausesofcancer
 Ther ootcauseofcanceri sdamagedDNA.
 Awi dev ar i
et yofenv ironment al forcescancausemut ations, permanent
damaget oDNA.
 Mut ationst hatl eadt ocancerar echar act erizedascar cinogeni c.
 Thel istofchemi calcar cinogensi slong.Moder nexampl esi ncludelinks
bet ween:
1)t hechemi cal cont entofci gar ettesmokeandl ungcancer ;
2)cer taindy esandbl addercanceri nthedy eandr ubberi ndustry;
3)l i
v ercancer si npar tsofAf r i
caandt heFarEastcausedbyaf latoxi
n, a
car
cinogenpr oducedbyamol di ni mpr oper l
yst or edf oodgr ain.
 Ionizi ngr adi ationandul tr
av i
olet( UV)l i
ghtal socanbemut ageni cand
car cinogeni c.
 Virusesal somaycausecancer .Humanpapi l
lomav irus( HPV)i sasexual ly
transmi tt
edi nf ect iont hataf termul tiplereinf ect ionsi st hecauseofmost
car cinomaoft hecer v i
x.
 Epst ei n-Bar rv i
r us( EBV)i simpl i
cat edast hecauseofsomel ymphomas, and
 hepat iti
sBandCv ir
us( HBVandHCV)ar ei mpor tantint hegenesi sof
hepat ocel lularcar cinoma.
 Asmal lper cent ageofcancerpat ientshav eani nheritedmut ati
oni nt heirgerm
cel l
s( ov aandsper m)t hatpredi sposet hem t odev elopmentofacer taint ype
ofcancer , whi cht heypasst osubsequentgener ations.
 Per hapst hemostwi del yknowni st heBRCAgene, amut atedv ersionofwhi ch
encour ages, butdoesnotguar ant ee, t
hedev el opmentofbr eastandov ar i
an
canceri nwomen.
 Themut antgenesf allintofourcat egor i
es: pr otooncogenes, tumor
suppr essor s,genest hatr egul ateapopt osis, andDNAr epairgenes.
 Car cinogenesi si samul ti
steppr ocess.Nosi ngl emut at i
oni nanyoft hegene
typesdi scussedabov ei ssuf fi
ci entt opr oduceaneopl asm, muchl essa
mal i
gnantone.Cancer sar i
sef rom anaccumul ationofmul tiplemut at i
ons: t
he
av eragebr eastorcol oncancerhas90di fferentmut at ions.

Thehal
lmar ksofneoplasia
Thefol
l
owi ngbiologi
ccapabil
i
tiesarethesev enhal
lmar
ksofneopl
asi
a.
1.Self
-suffi
ciencyofgrowt
h( “
go”)signal
s
2.Evasionofgr owthsuppr
ession(“
st op”
)signal
s
 3.Cel l
sdivi
dei ndefi
nit
ely(unli
mi t
edreproducti
on)
4.Av oidapoptosis(programmedcel ldeath)
5.Recr ui
tnutri
ent svi
agrowt hofnewbl oodsupply
(angiogenesi
s)
6.Invadenear bytissueandspr eadtodistantti
ssue(a
featureofmal ignantneoplasmsonl y)
7.Ev adeimmunesur vei
ll
ance( thecancerdetecti
onandel
i
minat
ionaspectof
t
heimmunesy stem)

Dy
splasia/Cai nsi tu
 Dysplasiai sthemi croscopicexpr essionoft heaccumul ati
nggenet icdefect
s.
Thedegr eeofdy splasiavari
esf r
om mi l
dt osev ereaccor di
ngt otheamountof
accumul atedgenet i
cdamage.
 Iti
scr i
tical t
ounder standthatdyspl asiadoesnotal way sprogresst o
malignancy .
 Atacer t
ai npoint,dy spl
asiabecomessev ereenought obecomecar ci
nomai n
sit
u, astat ethatiscancer“ i
nplace” .
 Carcinomai nsitui sneoplasiaconf inedt ot heepi t
helium.Sincei thasnot
penet r
atedt hebasementmembr ane, i
tcannotr eachbl oodv esselsor
lymphat ics(whi chl i
ebeneat hthebasementmembr ane)inor derto
met astasizet oot herlocati
ons.Thus, itisnotinv asi
v e.
 Nev ert
hel ess,atsomepoi ntthemal ignantcel lsacqui retheabili
tytoinvade:
thatis,topenet rat ethebasementmembr ane,andgai naccesst ov essel
sand
lymphat icsthatcancar ryittoanypar toft hebody .

Benignv s.malignant
 Abeni gntumori sonet hatusuall
ydoesnothav et
hecapacityt
ocausedeath.
Notableexcept i
onsar ebenignbraint
umor s, whi
chmaygr owslowlybutcan
causedeat hbyv i
rtueoft hei
rcri
ti
callocati
on.Forexample,ameningioma,a
benignneopl asm ofthemeni ngessurroundingthecent
ralnerv
oussy st
em,
cankillbycompr essingthebr ai
n.
 Amal ignanttumori sonet hathasthecapaci t
ytocausedeath.

I
.GROWTHRATE:
 Beni gn: Usuall
yslow
 Mal i
gnant :
Usual l
yrapid
I
I.LOCALI NVASI ON:
 Beni gn: Oft
encompr essest hesur r
oundingt i
ssueswithouti
nvadi
ngor
infi
lt
rati
ngt hem
 Mal i
gnant :
Usual l
yinfi
ltr
atesandi nv adestheadjacentti
ssues
I
II.GROSSFEATURES:
 Beni gn: Usuall
ysmal l;encapsulatedorwel l-
cir
cumscribed
 Mal i
gnant :
Usual l
ylarger;poorly-
circumscribedandirr
egular
I
V.MI CROSCOPI CFEATURES
Benign:
 Usual lyresembl esthet i
ssueofor i
ginclosely
 Pl eomor phism usuallynotpr esent
 Hy perchromatism absent
 Mi tosesmaybepr esentbutar eal waystypicalmit
oses
Malignant :
 Of t
enpoorr esembl ancet otissueofor i
gin
 Pl eomorphism of tenpr esent
 Hy per
chromat i
sm of tenpr esent
 Tumourgi antcel lspr esentwi t
hnucl earatypia
 Mi t
oti
cfiguresi ncreasedandar egenerall
yat ypicalandabnor mal
V.RECURRENCE( cancert hathascomeback, usuallyafteraper iodofti
medur ing
whicht hecancercoul dnotbedet ected):
 Beni gn:Usual lyabsent
 Mal i
gnant:Frequent lypr esent
 VI .METASTASI S(thedi scontinuousspr eadoft umorf r
om onesi t
etoanot her)
:
 Beni gn:Usual lyabsent
 Mal i
gnant:Frequent lypr esent
VII
.PROGNOSI S:
 Beni gn:Local compl i
cat i
ons-pr essureoft heexpandi ngt umormasson
nearbytissue
 Mal i
gnant:Deat hbyl ocal andmet astat
iccompl icati
ons-i nf
ectionorbleeding
from ul
cerationofsur faces; i
nfarcti
onorr upture’generalizedwast i
ng
(cachexi
a) ;
pr oductionofhor monesorot hermol eculest hataf f
ectdi
stant
organs