1

aLhology 1
O Llnk beLween cllnlcal and baslc sclences
O llnlcal paLhology sLudy of Lhe cause and mechanlsms of dlsease and Lhe effecLs of dlsease upon Lhe varlous organs and sysLems
O perlmenLal paLhology eperlmenLal sLudles on Llssues cell culLures or anlmal models
O PemaLology sLudy of blood dlsorders
O Mlcroblology sLudy of lnfecLlous dlseases
O lmmunology sLudy of Lhe body's defence mechanlsms
O CeneLlcssLudy of abnormal chromosomes and genes
O rognosls Lhe anLlclpaLed course of Lhe dlsease and flnal ouLcome ( le ure remlsslon morbldlLy morLallLy)
8ole of aLhologlsL
O ulagnosls cllnlcal supporL auLopsy research
1echnlques
O PlsLopaLhology eamlnaLlon of Llssues
O yLopaLhology eamlnaLlon of lsolaLed cells
O Surglcal paLhology eamlnaLlon of surglcal speclmens
O Cross paLhology vlsual observaLlons and descrlpLlons of organs and Llssues (macroscoplc)naked eye eamlnaLlon
O LlghL mlcroscope secLlons under Lhe mlcroscopecell morphology
O lecLron mlcroscope parLs of cellchanges ln organelles
O ellular level lmmunohlsLochemlsLryshows a speclflc proLeln blochemlcal assay blopsy cell culLure
O Molecular level analysls of unA 8nA and proLeln(chromosome analysls and unA sequenclng)
aLhology ls Lhe sLudy of dlsease
O aLhos dlsease" or sufferlng" logos sLudy"
O 1he sLudy of Lhe sLrucLural and funcLlonal changes ln cells Llssues and organs of Lhe body LhaL cause or are caused by dlsease
O ulsease resulL from some dlsLurbance Lo cells as a resulL of phys|ca| or env|ronmenta| harm or as a resulL of a genet|c aberrat|on
(lnherlLed or acqulred) Lhe paLLern of response of llvlng organlsms Lo ln[ury any devlaLlon from or lnLerrupLlon of Lhe normal sLrucLure
or funcLlon ldenLlfy based on physlcal appearance
O when cells fall Lo adapL Lo Lhe ln[ury C8 Lhe adapLlve mechanlsm lLself becomes harmful dlsease resulLs
O ldenLlfylng dlsease
O hyslcal slgns ob[ect|ve|y observed or measured by a physlclan (fever swollen ankle abnormal hearL beaL)
O llnlcal sympLoms sub[ect|ve complalnLs descrlbed by Lhe paLlenL (paln dlzzlness nausea) whaL Lhe paLlenL Lells you
O Lhese changes appear laLe ln Lhe dlsease process afLer a dlsease ls presenL and has been acLlng aL Lhe cellular level
lmpacL
O MorbldlLy lllness LhaL lmpalrs Lhe wellbelng and normal funcLlonlng of a paLlenL
O MorLallLy causlng Lhe deaLh of a paLlenL
O dlfferenL for dlfferenL age groups
O emalesmales for llfe epecLancy
O Males 6678
O emales 7082
O Jomenmen dle of sLroke
O Jomenmen for morLallLy raLe from lung cancer
O lncldence # of nJ cases ln a populaLlon
O slmllar Lo prevalence ln shorL llved and faLal dlseases
O revalence 1C1AL # of cases (new and old)
O lmporLanL for chronlc dlseases (always lncreaslng)
1op auses of MC81ALl1? ln anada
1 ardlovascular dlsease
2 ancer
3 erebrovascular dlsease (sLroke)
38 of all deaLhs ln '03
1op causes of MC88lul1? ln anada
1 ulsease of clrculaLory sysLem hearL aLLack sLroke
2 Cl dlsease
3 8esplraLory dlsease
based on # of hosplLallzaLlons
ancer lnlun ln anadanew cases
Males 1 rosLaLe 2 Lung 3 olorecLal
emale 18reasL 2 Lung 3 olorecLal
lncldence morLallLy
ancer uA1PS
1 LungboLh male and female
cancer prlmary dlsease of elderly (40 of new cases and 60 of deaLhs ln people over 70)
2

O Llology Lhe cause of a dlsease process (blologlcal agenLs chemlcal agenLs physlcal forces)
O e PepaLlc clrrhosls can be caused by vlrus (hepaLlLls) alcohol sLorage dlsorders
O aLhogenesls developmenL of a glven dlsease Lhe sequence of cellular evenLs LhaL Lake place from Llme of lnlLlal conLacL wlLh Lhe eLlologlc
agenL unLll Lhe epresslon of Lhe dlsease Lhe mechan|sm or how Lhe dlsease process evolves
O e Smoklng damage Lo resplraLory cells adapL/repalr geneLlc muLaLlon cancer
O aLhologlcal and morphologlcal manlfesLaLlons Lhe changes ln sLrucLure and funcLlon of Llssues organs and sysLems morphologlcal
changes are descrlbed as boLh Lhe gross anaLomlcal and mlcroscoplc changes LhaL are characLerlsLlc of dlsease
O ompllcaLlons and sequelae secondary consequences of a dlsease or procedure (e posL op lnfecLlon)
O pldemlology sLudy of dlsease ln popu|at|ons look for paLLerns ln dlsease or sLudy rlsk facLors LhaL predlspose Lhe dlsease lncldence and
prevalence
O healLh lndlcaLors llfe epecLance lnfanL morLallLy
Ceneral lasslflcaLlon of Lhe auses of ulsease
O ulsease resulLs from a varlable lnLeracLlon beLween hosL (geneLlc) and envlronmenLal facLors
O CeneLlcspredlsposale slckle cell dlsease
O nvlronmenLllfesLyle e LraumaLlc head ln[ury
O MosL dlseases are mu|t|factor|a| and due Lo lnLerplay beLween geneLlc and envlronmenLal componenLs (hearL dlsease dlabeLes cancer)
O ldlopaLhlcunknown cause Lhls area ls shrlnklng
O ulsease end polnL of cellular damage need Lo know whaL causes lL
CeneLlc auses
O CeneLlc alLeraLlons vary from 1 a slngle muLaLlon ln a unA base palr (slckle cell) Lo 2 rearrangemenLs of whole chromosomes (uown
syndrome)
O Slckle cell anemla abnormal 8globln gene of PbA molecule slngle base palr sub (gluval) consequences [am up blood vessels geL
lsochemla splenlc lnfarcLlon cuLaneous ulcer renal lnsufflclency chronlc paln pulmonary hyperLenslon avascular necrosls
O 1rlsomy 21 3 chromosomes on #21 consequences congenlLal hearL defecL menLal delay predlsposal Lo leukemla
O Sporadlc muLaLlons Lo unA LhaL occur LhoughouL llfe are more common Lhan lnherlLed geneLlc defecL
O An be lnherlLed 8u1 noL always someLlmes acqulred
O noL all lnherlLed geneLlc dlseases are manlfesLed aL blrLh (hunLlngLons's faLal neurologlcal dlsorder wlLh an auLosomal domlnanL paLLern ls
noL evldenL unLll adulLhood)
O noL all congenlLal dlseases (aL blrLh) are geneLlc (e rubella)envlronmenLal lnsulL
O ongenlLalborn wlLhgeneLlc
nvlronmenLal auses
*envlronmenLal causes can also be llfesLyle and personal hablLs
1 hyslcal agenLs
O Mechanlcal Lrauma cuLs MvA gunshoLs
O 1emperaLureburns heaLsLroke frosLblLe
O lecLrlc burns llghLnlng (naLural) or man made
O 8adlaLloncells whlch dlvlde mosL frequenLly are mosL senslLlve
O ALmospherlc pressure lncreased pressurelncreased nlLrogen dlssolved ln blood resurfaclng Loo qulck bubbles ln vascular sysLem
decreased pressure(hlgh alLlLude) gas bubbles ln blood and epanslon of gases**our cells are deslgned Lo work aL a cerLaln LemperaLure
2 hemlcal AgenLs
O nvlronmenLal (pesLlcldes) or lndusLrlal eposure ( asbesLos)
O olsons Lolns pesLlcldes organlc solvenLs heavy meLals sLrong aclds or alkalls componenLs of clgareLLe smoke
3 urugs
O 1herapeuLlc or recreaLlonal all drugs have slde effecLs
4 larLrogenlcany adverse condlLlon ln a paLlenL occurrlng as a resulL of LreaLmenL by a physlclan surgeon or oLher healLh professlonal
dlsease caused by medlcal Lherapy73lncldence of As
O Adverse evenLunlnLended ln[urles or compllcaLlons resulLlng ln deaLh dlsablllLy or prolonged hosplLal sLay LhaL arlse from healLh care
managemenL
3 lnfecLlons
O Manyvlruses and bacLerla Lo Lapeworms
O Slgns and sympLoms of an lnfecLlous dlsease are Lhe producL of Lhe lnherenL vlrulence or capaclLy of Lhe organlsms Lo cause dlsease Lhe hosL's
defence agalnsL lL and any Lherapy LhaL has been glven
O new and old lnfecLlous agenLs have had a recenL resurgence e new AluS SA8S Cld 18 malarla
O varleLy of responses mlld leLhal
6 Allergens
O A varleLy of eogenous and endogenous subsLances can Lrlgger lmmune reacLlons
AlLernaLlve lasslflcaLlons of ulseasesboLh geneLlc and envlronmenLal componenLs more pracLlcal
O A more deLalled classlflcaLlon of dlsease based on Lhe paLhogenesls or dlsease process
O 1 ln[urydue Lo chemlcal agenLs may be reverslble and Lhe cell/Llssue survlves or adapLs (aLrophy hyperLrophy hyperplasla) or lrreverslble
leadlng Lo deaLh of cell
3

O 2 lnflammaLlon some dlseases are LhoughL Lo be prlmarlly lnflammaLory (LonsllllLls appendlclLls) A chronlc lnflammaLory response may also
occur ln cerLaln allerglcLype reacLlons and wlLh cerLaln vlral or paraslLlc lnfecLlons
O 3 lnfecLlon one of Lhe mosL common forms of dlsease lnfecLlous organlsms can produce more serlous lllness ln Lhose whose lmmune sysLem
ls compromlsed eLenL of paLhology and dlsease depends on facLors of Lhe aLLacklng organlsm and hosL's responses
O 4 lmmunologlcal 8eacLlon normally proLecLlve buL may become ecesslve (allerglc reacLlons causlng anaphylacLlc shockle food allergles or
lnsecL blLes) or auLolmmune( LhyroldlLls or rheumaLold arLhrlLls) or may be absenL or depressed (prlmary Plv Slusno lmmune sysLem or
LreaLmenL relaLed chemoLherapy)
O 3 neoplaslanew growLh auLonomous prollferaLlon of cells usually causlng Lumours or masses can be benlgn (noL spreade mole) or
mallgnanL (can spread)
O MassLumourcancer cancermallgnanL neoplasla
O 6 MeLabollc or ndocrlne dlsorders of enzymes hormones or secreLory producLs (Lype ll dlabeLes) some are geneLlc
O 7 nuLrlLlonal deflclencles ln proLelns or calorles due Lo lnsufflclenL supply decreased absorpLlon LransporL or uLlllzaLlon (cellac dlsease) or
speclflc vlLamln or mlneral deflclencles (scurvy) fllp slde ecess calorles or obeslLy (hyperLenslon dlabeLes hearL aLLack cancer lncreased
rlsks)
O 8 vascular dlsease one of Lhe mosL common causes of deaLhnarrowlng of lmporLanL blood vessels (aLheroscleroslsplaque bulld up rupLure
leads Lo blood cloL) leads Lo hearL aLLacks and sLrokes and perlpheral vascular dlsease lack of blood supplylack of oygen
O sychologlcal facLors can boLh cause and effecL dlsease sLress may lead Lo menLal lllness or worsen elsLlng somaLlc dlsease also an
lmporLanL facLor ln dlsease caused by addlcLlon
aLhology 2 ell ln[ury AdapLaLlon and ell ueaLh
O llnlcal and eperlmenLal paLhology sLlll grounded ln Lhe bellefs of 1
Lh
cenLury Cerman sclenLlsL and sLaLeman kudo|f V|rchow LhaL
dlsease arlses noL ln organs or Llssues buL prlmarlly ln lndlvldual cells every cell comes from an ldenLlcal preelsLlng cell
O Jhen Lhe envlronmenL changes eceed Lhe capaclLy of Lhe cell Lo malnLaln homeostas|s we recognlze ce|| |n[ury
O AgenLs LhaL can cause ln[ury or presenL damaglng sLlmulus Lo Lhe cell
O hys|ca| agentsLrauma radlaLlon eLremes of LemperaLure changes ln pressure
O Chem|ca| agentsalr pollulanLs C pesLlcldes polsons Lolns drugs
O 8|o|og|ca| agentsmlcroorganlsms blologlcal Lolns
O Nutr|t|ona| or metabo||c a|terat|onsnuLrlLlonal deflclencles lschemlalack of blood supply(no bloodno oygendoesn'L geL rld of Lolc
meLabollLes) hypolalack of oygen (pneumonla anemla C polsonlng anolaLoLal absence of oygen)
O **noL all hypola ls lschemlc lschemlc cells wlll become hypolc
O Immune react|onsallergens auLolmmune dlsease
O Genet|c defectsslngle amlno acld subsLlLuLlon such as slckle cell dlsease chromosomal abnormallLles such as Lrlsomy 21 or uown
syndrome
O Ce||u|ar ag|ng (loss of lnLrlnslc repalr mechanlsms repeaLed heallng and repalr followlng eLernal ln[urles
O **reacLlon of Lhe cell Lo a sLress or damaglng sLlmulus can range from a mlld compleLely reverslble response Lo a longLerm adapLlve
change ln cell growLh Lo lrreverslble damage and cell deaLh
O 8everslble Lo lrreverslble polnL of no reLurnnoL well deflned
O 8esponse depends on severlLy of sLlmulus Llme frame over whlch lL ls eposed Lo Lhe sLressor and Lhe lndlvldual cell Lype and lLs
characLerlsLlcs (raLe of dlvlslon presence of proLecLlve mechanlsms lLs nuLrlLlonal or meLabollc sLaLe lLs blood supply)
O vulnerable cell componenLs cell membranes (crlLlcal for lonlc and osmoLlc homeosLasls) mlLochondrla (generaLlon of energy) proLeln
synLhesls and cellular unA **and cyLoskeleLon
ellular AdapLaLlonall can be physlologlc (happen normally ln body) or paLhologlc
O 8esponse Lo perslsLenL subleLhal ln[ury (chemlcal or physlcal) reflecLs an adapLaLlon of Lhe cell Lo Lhe envlronmenL achlevlng a new
sLeady sLaLe and preservlng cell vlablllLy
O AdapLlve responses regulaLlon of cell recepLors (up or down regulaLlon) or changes ln proLeln synLhesls and Lurn overadapLaLlons
lnclude changes ln cell slze( aLrophy or hyperLrophy) number (hyperplasla) or organlzaLlon (meLaplasla dysplasla)
O Atrophy lncreased proLeln degredaLlon and decreased proLeln synLhesls reduced demands leads Lo aLrophy of organs decrease ln
mass due Lo shrlnkage of cell slzemay have dlmlnlshed funcLlon buL A8 nC1 dead noL cell #
O uue Lo dlmlnlshed blood supply (lschemla) or dlmlnlshed nuLrlonal or Lrophlc facLors a new sLeady sLaLe ls reached ln whlch a smaller cell
ls able Lo survlve decrease work load(lmmoblllzaLlon) loss of lnnervaLlons decreased blood and nuLrlenL supply loss of endocrlne/hormonal
sLlmulus aglng degradaLlon of cellular proLelns plays a key role ln aLrophy 2 sysLems lnvolved
O Lysosomes conLaln powerful dlgesLlve enzymes LhaL degrade boLh molecules ouLslde cell(endocyLosls) or lnslde cell(auLophagy of
subcellular componenLs)
O ublqulLlnproLeasome paLhway cyLosollc and nuclear proLelns are LargeLed for degradaLlon by con[ugaLlon Lo a 76 amlno acld proLeln
ub|qu|t|n and degraded wlLhln a large cyLoplasmlc proLeolyLlc comple Lhe proteasome
O Autophagy resulLs ln lncreased number of auLophaglc vacuolesprocess ln whlch sLarved cell eaLs lLs own componenLs ln an aLLempL Lo
flnd nuLrlenLssomeLlmes accompanles aLrophy lysosomes wlLh undlgesLed debrls may perslsL ln cells as resldual bodles or may be
eLrudedllpofuscln plgmenLrepresenL lndlgesLed maLerlal
O **aLrophy can be physlologlcal or paLhologlcal physlologlcal aLrophynormal aglng(shrlnkage and loss of braln cells wlLh age)
paLhologlcal aLrophy dlsuse aLrophy of skeleLal muscle ln lmmoblllzed llmbs or denervaLlon aLrophy followlng loss of nerve lnpuL Lo muscle
4

O nypertrophy lncrease ln slze of elsLlng celldue Lo lncrease ln synLhesls of cellular proLeln and sLrucLural componenLs and organelles
responslble for produclng Lhemphyslologlcal or paLhologlcal ln response Lo lncreaslng funcLlonal demand or speclflc hormonal sLlmulaLlon no
new cells [usL blgger cells(lncapable of dlvldlngno cell dlvlslon)
O hys|o|og|c hypertrophy skeleLal muscles ln welghL Lralnlng
O atho|og|c hypertrophy cardlac muscle flbers ln response Lo lncreased workload as a resulL of sysLemlc hyperLenslon
(cardlomegaly)maladapLlon
O nypertrophy of SLk cells eposed Lo Lolns LhaL are meLabollzed ln S8 show hyperLrophy of Lhe 8 a compensaLory mechanlsm Lo
malmlze removal of Lols
O M|tochondr|a| a|terat|ons changes ln number slze and shape of mlLochondrla
O Cytoske|eta| a|terat|ons some drugs and Lolns lnLerfere wlLh Lhe assembly and funcLlons of cyLoskeleLal fllamenLs or resulL ln abnormal
accumulaLlons of fllamenLs
O Card|ac hypertrophy 2 slgnals mechanlcal Lrlggers(sLreLch) or Lrophlc Lrlggers(acLlvaLlon of alpha adrenerglc recepLors
O nyperp|as|a lncreased number of cell caused by cell dlvlsloncan be precursor Lo carclnoma
O PyperLrophy and hyperplasla ofLen occur LogeLher as a normal response Lo sLlmull boLh occur ln uLerlne smooLh muscle durlng
pregnancy ln response Lo esLrogen hyperLrophy of muscles durlng welghL Lralnlng
O hyslologlc hyperplasla hormonal hyperplasla( growLh of female breasL) and compensaLory hyperplasla ( occurs when a porLlon of Lhe
Llssue ls removed or dlseased)
O ompensaLory hyperplasla when a porLlon of Llssue ls removed
O aLhologlcal responsescaused by ecesslve hormonal or growLh facLor sLlmulaLlon hyperLrophy of cardlac muscle flbres occurs ln
response Lo lncreased workload as a resulL of sysLemlc hyperLenslon (card|omega|y)lefL venLrlcle works harder so lncreased
pressurehyperLenslonmuscle slze lncreasesnarrowlng lumenhearL muscle cells don'L dlvlde ecesslve sLlmulaLlon of normal uLerus by
esLrogen may resulL ln endomeLrlal hyperplaslaunopposed esLrogen ln uLerusendomeLrlum keeps prollferaLlng
O 8oLh uLerus durlng pregnancy ln response Lo esLrogen hyperplasla and hyperLrophy
O Metap|as|a lf Lhe long Lerm envlronmenL becomes unsulLable for cerLaln cell Lypes Lhey may change |nto a d|fferent adu|t ce|| type
(meLaplasla)may resulL ln decreased funcLlon or lncreased rlsk for mallgnancy cells ln bronchl of smokers (paLhologlc) change from clllaLed
columnar cells Lo squamous cells(Lougher Lhan columnar cells buL lack cllla)LhoughL Lo arlse from geneLlc reprogrammlng of sLem cellsalLhough
Lhe meLaplasLlc squamous eplLhellum has survlval advanLages lmporLanL proLecLlve mechanlsms are losL Lhe lnfluences LhaL lnduce meLaplasLlc
LransformaLlon lf perslsLenL may predlspose Lo mallgnanL LransformaLlon of Lhe eplLhellum physlologlc cervl durlng puberLy
O Metap|as|a may a|so occur |n mesenchyma| ce||s but |ess c|ear|y as an adapt|ve response
O **ln all cases of growLh adapLaLlon lf Lhe sLlmulus ls removed Lhe Llssue reverLs back Lo resLlng sLaLe conLrasLed wlLh auLonomous
growLh ln neoplasla
O Dyspas|a so much dlsorganlzaLlon and change LhaL cells have a chance Lo become mallgnanLmay resulL from progresslve meLaplasla
8everslble and lrreverslble ell ln[ury
O uncLlonal acLlvlLy ls losL relaLlvely qulckly as a resulL of blochemlcal derangemenLs 8u1 morphologlcal changes of cell ln[ury and deaLh
lag far behlnd hearL cells lose ablllLy Lo conLracL 12 mlns of lschemla buL do noL dle unLll 2030 mlns afLer changes ln cell ulLrasLrucLure may noL
be apparenL unLll several hours followlng lschemlc ln[ury
O arly sLages/mlld forms of ln[ury funcLlonal and morphologlcal changes are enLlrely reverslble lf sLlmulus ls removedln[ury has noL
progressed Lo severe membrane or nuclear damage
O onLlnulng damage lrreverslblecannoL recover and dles
O 2 Lypes of cell deaLh necros|s and apoptos|s dlffer ln morphology mechanlsms and cause (paLhologlcal or physlologlc)
O ell ln[ury can essenLlally go rlghL Lo apopLosls or reverslble cell ln[ury
O 8esponse Lo ln[ury depends on Lype duraLlon and severlLy
O onsequences depend on Lype sLaLe and adapLablllLy of cell
O ell deaLh ls ofLen dlfflculL Lo see rlghL afLer because vlslble changes occur laLer on ulLrasLrucLural llghL mlcroscope gross
morphologlcal changes
8everslble ell ln[ury
O Cnce a cell shuLs down lL doesn'L have long Lo llve
O 8esponse Lo an acuLe or mlld sLree/sLlmulus
O 8everslble lf sLlmulus removed!
O Pallmarks reduced oldaLlve phosphorylaLlon A1 depleLlon cellular swelllng
O ldney very suscepLlble Lo lschemla because relles so heavlly on adequaLe blood flow
O ln[ury caused by chemlcal or blologlcal Lolns vlral or bacLerlal lnfecLlons lschemla or hypola ecesslve heaL or cold produce ce||u|ar
or hydrop|c swe|||ng lncrease ln cell volume characLerlzed by large pa|e and vacuolaLed cyLoplasm and a normally locaLed nucleusresulLs from
lmpalrmenL of Lhe process LhaL conLrols lon concenLraLlon ln cyLoplasm agenLs can lmpalr Lhe energy dependenL na++ A1ase leasdlng Lo
accumulaLlon of sodlum ln Lhe cell lncrease ln waLer ln Lhe cell Lo malnLaln lsoosmoLlc condlLlons and cell swells mlLochondrla may also swell
clsLernae of 8 becomes dllaLed blebs may form on M
O Morphologlcal changes
O nydrop|c swe|||ngd||at|on of c|sternae of Lk |mpa|rment of ce|| vo|ume regu|at|on |nf|ux of sod|um eff|ux of potass|um start to |ose
ce||ce|| |ntegr|ty nuc|eus st||| okay nuc|ear chromat|n c|ump|ng r|bosomes |ose funct|on so decreased prote|n product|on b|ebs on M (effects
|ntegr|ty)
O 8emoval of sLlmulus reverslble changes and reverL back Lo normal sLaLe
3

O AnoLher form of reverslble adapLaLlon Lo cell sLressorsfaLLy change or abnormal accumulaLlon of Lrlglycerldes wlLhln cells appearance
of small or large llpld vacuoles ln Lhe cyLoplasmoccurs malnly ln cells lnvolved ln and dependenL on faL meLabollsm
O ulLrasLrucLural changes M alLeraLlons such as blebblng blunLlng or dlsLorLlon of mlcrovllll and loosenlng of lnLracellular aLLachmenLs
mlLochondrlal changes dllaLlon of Lhe 8 wlLh deLachmenL of rlbosomes and dlssoclaLlon of polysomes and nuclear alLeraLlons wlLh clumplng of
chromaLln
lrreverslble cell ln[ury and cell deaLh
O AcuLe severe sLress or prolonged unrelleved sLress
O Cverwhelmlng ln[ury aL a raLe where cell cannoL adapL necros|s or ce|| death resu|t
O Necros|s sLrucLural changes |ntense eos|noph|||a (p|nkness|ose kNA wh|ch wou|d norma||y sta|n b|ue)) of the cytop|asm and
pyknos|s (shr|nkage) karyorrhex|s (the pyknot|c nuc|eus fragments) and karyo|ys|s (d|sso|ut|on) of nuc|eus |nf|ammatory |nf||trateneutroph||s
and macrophages |ngest dead ce||s(pus) changes ln sLrucLures and funcLlon
O 2 ma[or mechanlsms of deaLh necrosls and apopLosls
O necroslsresulL of A1PCLCClAL lnsulL
O 1ypes of necrosls
O Coagu|at|ve mosL common formmlcroscoplcally all changes descrlbed above are seecells appear ghosLs(no nucleuskaryolysls) of
Lhemselves ln whlch Lhe baslc sLrucLural ouLllne of Lhe coagulaLed cell perslsLs for a number of days Lyplcal of |schem|a (hearL kldney cells) no
bloodno enzymes
O L|quefact|ve rapld loss of Llssue archlLecLure and dlgesLlon of Lhe dead cellsmosL ofLen seen ln CNS (bacter|a| damage) or lung seen ln
area of lnfarcLlon due Lo acLlon of hydrolyLlc enzymes mushy"
O Iat speclflc Lo faL Llssue released enzymes dlgesL faL LhaL complees wlLh calclum Lo form chalkywhlLe deposlsLs pancreaLlLls damage
Lo breasL LlssueresulLs from release of acLlvaLed pancreaLlc llpases
O I|br|no|d seen ln lmmune reacLlons lnvolvlng b|ood vesse|spromlnenL when complees of anLlgens and anLlbodles are deposlLed ln Lhe
walls of arLerles lnflammaLlon of vessels flbrln leaks lnLo wall of vessel seen under mlcroscope
O Caseous sofL frlable cheesy maLerlaltubercu|os|s Llssue archlLecLure ls compleLely obllLeraLed and cellular ouLllnes cannoL be
dlscerned enclosed wlLhln a dlsLlncLlve lnflammaLory border can spread Lo resL of body
O **gangrenous necros|scoagulaLlve necroslsweL gangrene (usually of llmb) when Lhere ls superlmposed lnfecLlon wlLh a llquefacLlve
componenL lf necroLlc componenL drles ouL (wlLh no lnfecLlon) lL becomes dark black and mummlfleddry gangrene compromlsed vascular
supply
O na||marks
O Swelllng of 8 and loss of rlbosomes lysosome rupLure and release proLeolyLlc enzymes myelln flgures swollen mlLochondrla and
amorphous denslsLles nuclear condensaLlon blebblng rlbosomes floaL away membrane rupLures ouL of conLrol shuL down lnablllLy Lo reverse
mlLochondrlal dysfuncLlon
rogrammed ell ueaLhApopLosls
O Apoptos|s Lhe morphologlc manlfesLaLlon of programmed cell deaLh and ls dlsLlncL from necrosls (Lhe unconLrolled process of cell deaLh
ln response Lo overwhelmlng ln[urLy) energy dependent process spec|f|ca||y des|gned to sw|tch off undeeded or damaged ce||s and e||m|nate
them can occur under physlologlc(embryogenels ln shaplng flngers and Loes lnvoluLlon of Lhymus durlng developmenL removal of lnfecLed of
damaged cells) or paLhologlc (followlng radlaLlon ln[ury)
O **phys|o|og|c(programmed destruct|on or "prun|ng" ce|| dur|ng deve|opment |oss of hormone or growth factor s|gna|s endometr|um
neutroph|| and |ymphocytes ce|| |oss]turnover |n pro||ferat|ng ce||s) or patho|og|c(e||m|nat|on of genet|ca||y a|tered or damaged ce||s
O na||marks of apoptos|s nuclear dlssoluLlon wlLhouL compleLe loss of membrane lnLegrlLy cell shrlnkage fragmenLaLlon Lo form
apopLoLlc bodles (conLalned ln vacuoles) nC lnflammaLory reacLlon phagocyLes eaL sLuff up
O onLrolled manner acLlve energy dependenL LlghLly regulaLed
O ApopLoLlc cells lnlLlaLe own deaLh by Lhe acLlvaLlon of proLeases known as caspases and endogenous endonucleases LhaL breakdown Lhe
cell nucleus and cyLoskeleLon (paLhways can be Laken mlLochondrlal paLhway or deaLh recepLor paLhway) cell nucleus collapses cell shrlnks and
ls cleaved lnLo membranebound clumps encloslng organelles (apopLoLlc bodles) membrane bound maLerlal ls recognlzed and qulckly engulfed
by phagocyLlc cells
O Mechanlsms of ApopLosls
O M|tochondr|a| pathway (Intr|ns|c) Lrlggered by loss of survlval slgnals unA damage and accumulaLlon of mlsfolded 8 proLelns (8
sLress) assoclaLed wlLh leakage of proapopLoLlc proLelns from mlLochondrlal membrane lnLo Lhe cyLoplasm where Lhey Lrlgger caspase acLlvaLlon
lnhlblLed by anLlapopLoLlc members of Lhe 8cl famlly whlch are lnduced by survlval slgnals lncludlng growLh facLors |n[ury8c|2 m|tochondr|a
O Death receptor (extr|ns|c) pathway responslble for ellmlnaLlon of selfreacLlve lymphocyLes and damage by cyLoLolc 1 lymphocyLes ls
lnlLlaLed by engagemenL of deaLh recepLors on cell surface (members of Lhe 1NI recepLor famlly) by llgands on ad[acenL cells
O **both pathways |ead to "exectut|oner caspases"endonuclease acLlvaLlonbreak down of cyLoskeleLon sLlll remalns wlLhln cell
membrane phagocyLes come ln and clean up
O ApopLoLlc cells have phophaLldylserlne presenL on Lhe ouLer layer of membranerecognlzed by macrophages cells LhaL are dylng by
apopLosls secreLe soluble facLors LhaL recrulL phagocyLesprevenLs release of cellular componenLs some epress adheslve glycoproLelns LhaL are
recognlzed by phagocyLes
O Lxamp|es of apoptos|s growLh facLor deprlvaLlon (mlLochondrlal paLhway) unA damage(p33 accumulaLlon) accumulaLlon of mlsfolded
proLelns apopLosls of selfreacLlve lymphocyLes cyLoLolc 1 lymphocyLe medlaLed apopLosls
O MagnlLude/Lype of ln[ury sLlmulus deLermlne wheLher cell undergoes necrosls or apopLosls
O Severe damaglng sLlmull necrosls
6

O Lowergrade sLlmull and lmmunemedlaLed damageapopLosls
O **how much A1 ls avallable afLer cell damage bc apopLosls ls energy dependenL lf Lhere ls severe depleLlon of A1 Lhen follow
necroLlc paLhway
Ieature Apoptos|s Necros|s
lnducLlon hyslologlcal or paLhologlcal sLlmull uue Lo paLhologlcal ln[ury (hypola
Lolns)
eLenL Slngle cells Croups of cells
8lochemlcal evenLs mechanlsms Cene acLlvaLlon energy dependenL
fragmenLaLlon of unA by
endogenous endonucleases and
cleaved lnLo regular nucleosomal
fragmenLs (ladderlng) breakdown of
cyLoskeleLon by proLeases
lmpalrmenL or cessaLlon of lon
homeosLasls depleLlon of A1 lnflu
of sodlum waLer and calclum cell
membrane damage unA fragmenLed
lrregularly may be medlaLed by free
radlcals
ell membrane lnLegrlLy MalnLalned losL
Morphology ell shrlnkage fragmenLaLlon Lo
form apopLoLlc bodles wlLh dense
chromaLln
ell swelllng and lysls swelllng and
dlsrupLlon of organelles nucleus
pyknosls karyorrhels karyolysls
lnflammaLory response none ?es
aLe of dead cells lngesLed (phagocyLosed) by
macrophages
lngesLed(phagocyLosed) by
neuLrophlls and macrophages
O atho|og|ca| ca|c|f|cat|on
O 1 Dystroph|c occurs ln necroLlc or degeneraLlve Llssue calclum blndlng Lo dead Llssue abnorma| t|ssue norma| ca|c|um |eve|s
O 2 Ma||gnant deposlLlon of calclum ln normal Llssues wlLh hlgh blood calclum levels e uefecL ln paraLhyrold hormone (lncreases blood
calclum levels) norma| t|ssue abnorma| ca|c|um |eve|s
Mechanlsms of ell ln[ury
O uepends on Lype of ln[ury and Lhe ln[ured cell
CeneraLlon of reacLlve oygen specles (8CS)
O arLlally reduced or reacLlve oygen specles (superolde anlon hydroyl radlcal and hydrogen perolde) llkely cause of cell ln[ury
formed vla acLlon of lonlzlng radlaLlon (hydrolysls of waLer produces hydroyl radlcals resulLlng ln unA damage and apopLosls ln rapldly dlvldlng
cells) durlng reperfuslon of Llssues followlng a perlod of lsochemla ln Lhe presence of ecess oygen and normally ln lnflammaLory cells all of
Lhese molecules possess a free elecLron whlch makes Lhem hlghly reacLlve can lnlLlaLe llpld peroldaLlon leadlng Lo loss of membrane lnLegrlLy
crossllnk essenLlal proLelns damage unA or form secondary damaglng 8CS (llpld perolde radlcals peroynlLrlLe)
O 1hese molecules are formed durlng normal meLabollsm and oygen resplraLlonbody has mechanlsms Lo deLolfy sponLaneous decay
(superolde breaks down ln Lhe presence of waLer lnLo oygen and perolde) superolde dlsmusLase (converLs superoude Lo hydrogen perolde
and oygen) caLalase (converLs hydrogen perolde Lo waLer and oygen) or gluLaLhlone peroldlse (reducLlon of hydrogen perolde Lo waLer)
O ndogenous or eogenous anLloldanLsvlLamln A and offer some proLecLlon agalnsL free radlcals
lschemlc and Pypolc ell ln[ury
O Ischem|a reducLlon or lnLerrupLlon of blood flow mosL common Lype of cell ln[ury lmporLanL cause of coagulaLlve necrosls can ln[ure
Llssues AS18 Lhan reduced levels of oygen alone (hypola) slnce boLh oygen and subsLraLes for glycolysls and conLlnued A1 generaLlon
dlsappear
O uecreased oygen compromlses resplraLlon ln mlLochondrla damaglng Lhe ablllLy Lo produce A1
O uecreased A1 lmpalrs Lhe ablllLy of cells Lo pump lons and waLer (vla na+/+ A1ase) wlLh Lhe subsequenL accumulaLlon of lnLracellular
sodlum and Lhe dlffuslon of poLasslum ouL of cell
O neL galn of sodlum ls accompanled by an lsoosmoLlc galn of waLer acuLe welllng and ln Lhe swelllng of cellular componenLs wlLh
damage and rupLure Lo cell M
O uecreased A1 lncreased anaeroblc glycolyslsdepleLlon of glycogen sLores wlLh a bulld up of lacLlc acld ln cell (decreased pP)
O uecreased A1 and P rlbosomes deLach from rough 8 wlLh a reducLlon ln proLeln synLhesls
O **lf oygen ls resLoresall of above dlsLurbances are reverslble
O ** lf lschemla and hypola conLlnue worsen mlLochondrla funcLlon and lncreaslng membrane permeablllLy cause furLher deLerloraLlon
wlLh lrreverslble ln[ury and
O 8elease of proLeolyLlc enzymes from Lhelr normal comparLmenLs ln Lhe cellwldespread damage
O alclum lncreases ln cells due Lo pump fallure (aA1ase) acLlvaLes many enzyme sysLems lnapproprlaLely leadlng Lo furLher cell
damage some enzymes aLLack cellular skeleLal proLelns cells become abnormally fraglle membrane damage ls crlLlcal Lo Lhe developmenL of
leLhal cell ln[ury
O uegraded cell membrane releases proLelns lnLo perlpheral clrculaLlon means of deLecLlng Llssuespeclflc cell ln[ury and deaLh by
measurlng Lhelr levels ln blood serum samples (hearL muscle conLaln lsoform of creaLlne klnase and LroponlnelevaLed ln blood followlng hearL
aLLack)
lschemla/8eperfuslon ln[ury
O 8esLoraLlon of blood flow can resulL paradolcally ln addlLlonal cell ln[ury cells are losL durlng lschemlc eplsode and afLerwards
reperfuslon of lschemlc Llssues may cause furLher damage by
7

O 8esLoraLlon of blood flow baLhes cells ln hlgh concenLraLlons of calclum when Lhey may noL be able Lo fully regulaLe lLs lnLracellular
levelacLlvaLlng desLrucLlve enzymaLlc paLhways
O uamaged mlLochrondrla ln compromlsed cells may yleld lncreased producLlon of 8CS
O Local lncrease of lnflammaLory cells LhaL release hlgh levels of 8CSpromoLe addlLlonal membrane and mlLochondrlal damage
O ln[ured cells may have compromlsed anLloldanL defense mechanlsms
hemlcal or drugrelaLed cell ln[ury
O ulrecL (heavy meLals chemoLherapy) or lndlrecLly (followlng meLabollsm Lo acLlve meLabollLesl4 ls meLabollzed by llver 430 enzyme
Lo a hlghly reacLlve LrlchloromeLhyl free radlcaLl lnLermedlaLe whlch beglns a cascade of llpld peroldaLlon and cell membrane damge
O 430 mled funcLlon oldase sysLemresponslble for Lhe meLabollsm of a varleLy of drugs and chemlcals of whlch also form acLlve
ln[urlous meLabollLes
lnLracellular AccumulaLlons
O ells sLore faLs glycogen vlLamlns and mlnerals for use ln general cell meLabollsmalso sLore producLs of Lurnover as endogenous
plgmenLs (degraded phosphollplds as goldenbrown granules and Jear and Lear" plgmenL ||pofusc|n wlch lncreases wlLh age me|an|n ls an
lnsoluble brownblack plgmenL found ln skln and braln cells hemos|der|n ls Lhe lronrlch brown plgmenL derlved from Lhe breakdown of 88s(leLs
you know Lhere was bleedlng ln pasL)
O nemos|deros|s ecess lron sLorage ln skln pancreas hearL kldneys and endrocrlne glands can damage vlLal organ
O MosL common eogenous plgmenL carbon(alr polluLlon)lnhaled and deposlLed ln Lracheobronchlal lymph nodes and lung Llssue as
you geL older lL lncreasesmacrophages engulf lL buL can'L geL rld of lL so [usL slL Lhere
O 8enal Lubules lncreased absorpLlon of urlnary proLelnproLelns leak lnLo urlne
O lasma cellsend sLage 8 cells lncrease producLlon of lgmulLlple myeloma
O lnherlLed dlsorders of meLabollsm may lead Lo abnormal accumulaLlon of meLabollLes ln cells (glycogen sLorage dlseases comple llplds
lronhemochromaLoslsabnormal lron absorpLloncan'L geL rld of lron))
O Iatty change]steatos|s llnked Lo lnLracellular accumulaLlon of faL elLher because of lncreased dellver of faL Lo Lhe cell (sLarvaLlon
dlabeLes) an lmpalrmenL of faL meLabollsm wlLhln Lhe cell (ln llver cells ln alcohollsm) or decreased synLhesls of apollpoproLelns for LransporL ouL
of cell (proLeln malnuLrlLlon l4 LolclLy)
O L|p|d accumu|at|on slgn of reverslble cell ln[urysLeaLosls(faLLy change)
O Small vacuoles of faL appear LhroughouL Lhe cyLoplasm or may coalesce Lo form on large vacuole dlsplaces nucleus
O Llverwhere mosL faLs are sLored and meLabollzedsuscepLlble Lo faLLy change buL may also occur ln hearL kldney skeleLal muscle and
oLher organs as a resulL Lo Loln eposure ( a|coho|(#1) l4) proLeln malnuLrlLlon or sLarvaLlon dlabeLes obeslLy and anolaln llver free faLLy
aclds enLer and undergo a number of blologlcal paLhways esLerfled Lo Lrlglycerlde and palred wlLh apoproLeln and formed lnLo llpoproLeln whlch
elLs
O lMAl8u faL meLabollsm due Lo
O AlLeraLlon ln upLake of free faLLy aclds alLeraLlon ln meLabollsm alLeraLlon ln LransporL ouL of cell anola LCP nASP nonalcohollc
sLeaLohepaLlsls(noL from alcohol buL from dlabeLes and obeslLy) sLarvaLlon (body sLarLs Lo make more faLs)
O ln anada mosL common cause of faLLy acld change ln llver ls due Lo ALCPCL A8uS dlabeLes wlLh obeslLy also conLrlbuLes
O OanLhomas clusLers of foamy macrophages
O ALherocsclerosls smooLh muscle cells and macrophages are fllled wlLh llpld vacuoles
O 8ussel 8odles marked accumulaLlon of newly synLheslzed lmmunoglobullns LhaL may occur ln Lhe 88 of some plasma cells formlng
rounded eoslnophlllc 8ussel bodles
O **faLLy change ls enLlrely reverslble lf Lhe sLlmulus ls removed!
O 3 maln paLhways of abnormal lnLracellular accumulaLlons defecL ln proLeln foldlng or LransporL lack of enzyme lngesLlon of lndlgesLlble
maLerlals abnormal meLabollsm
O holesLerol deposlLlon resulL of defecLlve caLabollsm and ecesslve lnLake ln macrophages and smooLh muscle cells of vessel walls ln
aLherosclerosls
O ueposlLlon of proLelns reabsorbed proLelns ln kldney Lubules lmmunoglobullns ln plasma cells
O ueposlLlon of glycogen ln macrophages of paLlenLs wlLh defecLs ln lysosomal enzymes LhaL break down glycogen (glycogen sLorage
dlseases)
O aLhologlcal calclflcaLlons
O uysLrophlc calclflcaLlon deposlLlon of calclum aL slLes of cell ln[ury and necrosls
O MeLasLlaLlc calclflcaLlon deposlLlon of calclum ln normal Llssues caused by hyperglycemla
O AccumulaLlons normal cellular producLs (waLer llplds proLeln) abnormal subsLances (e or endogenous) plgmenLs
O Jhy accumulaLlons?
O lnadequaLe raLe of meLabollsm geneLlc or acqulred defecLs ln meLabollsm packlng or LransporL abnormal eogenous subsLances
O Alpha1anLlLrypsln deflclency geneLlc or acqulred defecLs ln meLabollsmlncreased parLlally folded proLelns so decreased proLease
lnhlblLor acLlvlLy (doesn'L geL ouL of llver cells)auLosomal recesslveloss of lnhlblLor
O omes lnLo play ln lungs emphysema lncrease ln proLeases break down proLelns (lnsulL) more common ln people who smoke
O 1A1 ls a proLease lnhlblLorkeeps Lhlngs under conLrol
O may also cause clrrhosls all Lhe mlsfolded proLelns
**cell deaLh ls also a normal and essenLlal process ln embryogenesls Lhe developmenL of organs and malnLenance of homeosLasls
*cell deaLh Lyplcally precedes ulLrasLrucLural llghL mlcroscoplc and grossly vlslble morphologlc changes
*necrosls ls always a paLhologlc process apopLosls serves many normal funcLlons and ls noL necessarlly assoclaLed wlLh paLhologlc cell ln[ury
8

*cellular funcLlon may be losL long before cell deaLh occurs and Lhe morphologlc changes of cell ln[ury (or deaLh) lag far behlnd boLh**effecL
molecular Lhan blochemlcal level
**2 phenomena characLerLlze lrreverslblllLy Lhe lnablllLy Lo reverse mlLochondrlal dysfuncLlon (lack of oldaLlve phosphorylaLlon and A1
generaLlon) and profound dlsLurbance sln membrane funcLlon
*cell deaLh due Lo lack of oygen lncreased eoslnophlla
*dead cells may become calclfled
*Lhe cellular response Lo ln[urlous sLlmull depends on Lhe Lype of ln[ury lLs duraLlon and lLs severlLy
*Lhe consequences of an ln[urlous sLlmulus depend on Lhe Lype sLaLus adapLablllLy and geneLlc makeup of Lhe ln[ured cell
*cell ln[ury resulLs from funcLlonal and blochemlcal abnormallLles ln one or more of several essenLlal cellular componenLs
*lschemlc anaeroblc energy generaLlon ceases bc glycolysls ls lnhlblLed by accumulaLlon of meLabollLeslschemla damages Llssues fasLer Lhan does
hypola
*loss of A1 leads Lo Lhe fallure of many energy dependenL cellular sysLems lncludlng lon pumps depleLlon of glycogen sLores reducLlon ln proLeln
synLhesls
*ApopLosls lmporLance ln physlologlc slLuaLlons Lhe programmed desLrucLlon of cells durlng embryogeneslsmake many more neurons Lhan we
need mosL are desLroyed lnvoluLlon of hormonedependenL Llssues upon hormone deprlvaLlons cell loss ln prollferaLlng populaLlons deaLh of
cells LhaL have served Lhelr useful purpose ellmlnaLlon of poLenLlally harmful selfreacLlve lymphocyLes cell deaLh lnduced by cyLoLolc 1
lymphocyLes
*apopLosls ln paLhologlcal condlLlons ellmlnaLes cells LhaL are geneLlcally alLered or ln[ured beyond repalr wlLhouL ellclLlng a severe hosL reacLlon
Lhus keeplng Lhe damage as conLalned as posslbleunA damage accumulaLlon of mlsfolded proLelns cell ln[ury ln cerLaln lnfecLlons paLhologlcal
aLrophy ln parenchymal organs afLer ducL obsLrucLlon

aLhology 3lnflammaLlon
O Jhere Lhere ls necrosls lnflammaLlon occurs end of lnflammaLlonbeglnnlng of heallng
O 1lssue ln[ury sLlmulaLes a serles of reacLlons Lo occur aL Lhe slLe of ln[ury lnflammaLory reacLlon purpose
O 1 1o desLroy or llmlL Lhe spread of Lhe ln[urlous agenL
O 2 1o allow for repalr or replacemenL of Lhe damaged Llssues
O lnflammaLlon characLerlsLlc response of llvlng Llssues Lo an ln[ury
O A) lnflammaLlon ls a dynam|c ever changlng process conslsLlng of a chaln of reacLlons whlch succeed or overlap eachoLher lL ls nC1 a sLaLlc
slLuaLlon
O 8) Lhe ln[ury musL be non|etha| lf Lhe ln[ury ls of such severlLy Lo desLroy Lhe Llssue aL Lhe ouLseL no lnflammaLory response can occur ln LhaL
Llme requ|res energy and oxygen from ce||s requ|re that the |nd|v|dua| can respond need blood flow and oygen for an lmmune response
O ) Lhe lnflammaLory response ls nonspec|f|c Many dlverse ln[urles can cause lnflammaLlon and Lhe lnlLlal sLages of Lhe lnflammaLory acLlon
are ldenLlcal ln almosL all of Lhe Llssues lrrespecLlve of Lhe Lype of ln[ury 1he lnLenslLy duraLlon and ouLcome of Lhe lnflammaLory reacLlon
are modlfled by facLors perLalnlng Lo Lhe hosL as well as Lo Lhe ln[urlous lnsulL lL ls sLereoLyped and very predlcLable
O Causes of |nf|ammatory react|on (essent|a||y the same stuff as ce|| |n[ury and ce|| death)
O 1 Infect|on e lnvaslon and mulLlpllcaLlon wlLhln Llssues by organlsms bacLerla fungl vlruses and proLozoacause damage by release of
Lolns whlch dlrecLly desLroy hosL cells
O **do noL confuse lnflammaLlon wlLh lnfecLlon an lnfecLlon almosL always wlll cause an lnflammaLory response however Lhe eLlologles of an
lnflammaLory response are dlverse usually a relaLlvely large lnflammaLory reacLlon wlll occur ln response Lo an lnfecLlon
lnfecLlonlnflammaLlonlL ls a Lype of lnflammaLlon
O 2 1rauma peneLraLlng ln[ury (sLab wound wood sllver) blunL Lrauma Lhermal ln[ury (ecesslve heaL or cold) chemlcal ln[ury (acld or alkall)
O 3 Immuno|og|ca||y med|ated humoral or cellular allergles vacclnaLlons
O 4 Loss of b|ood supp|y (lschemla) decreased C2
O lnflammaLlon can be dlvlded lnLo vascular and cellular evenLs boLh are medlaLed by chemlcal facLors buL boLh evenLs acLually occur
concomlLanLly
1rlangle of lnflammaLlon ells vessels (where Lakes place) hemlcal MedlaLors (makes Lhlngs happen) all happens aL once
1 Vascu|ar Lvents
O Lewls's 1rlple 8esponse 1 allor (palevery brlef) 2 8edness 3 swelllng
O A)lmmedlaLely followlng ln[ury LranslenL vasoconstr|ct|on of arLerloles medlaLed by nerves Lo Lhe smooLh muscle and wlLhln Lhe arLerlolar
walls (neurologlcal response) brleflasLs for 3 mlnsmakes area pale (less blood flow Lo slLe of ln[ury
O MlcroclrculaLlonbaslc unlL
O 8)neL vasod||at|on of venules caplllarles arLerloles (more hemodynamlcally lmporLanL) openlng of precap|||ary sph|ncters of arLerloles
openlng up of new cap|||ary beds openlng of arter|a| venous shunts ln caplllary bed resu|t lncreased blood flow Lo Lhe ln[ured area (appears
red or hyperaem|c on gross eamlnaLlonsource of redness and warmLh)
O lf mlld ln[ury vascular changes may noL proceed any furLher Lhan Lhls
O 8edness and heaL due Lo chemlcal medlaLors
O )More severe ln[ury vasodllaLlon followed by slowlng of blood flow
O u) vasodllaLlon ofLen accompanled by |ncreased vascu|ar permeab|||tyouLpourlng of flulds and proLelns from Lhe blood vessels affecLs flrsLly
and predomlnanLly venu|es caplllarles and arLerloles are also lnvolved vessels are llned wlLh endoLhellal cells (normally flaL) LhaL have falrly
LlghL [uncLlons (noL Loo much leaks Lhrough) durlng lnflammaLlon chemlcal medlaLors are released (e PlsLamlne) LhaL make endoLhellal cells
conLracL (scrunch up) whlch creaLes larger gap a loL more subsLance leaks ouL (cells proLelns)


O Loca| hemoconcentrat|on vlscoslLy of blood ls lncreased as a resulL of fluld loss from Lhe vessellead Lo packlng or sludglng or 88s
Lherefore s|ow|ng b|ood f|ow someLlmes slowed Lo Lhe polnL of sLasls or Lhrombls (cloLLlng) Lhrombls ln vessels may occur due Lo a second
mechanlsm ln severe ln[urles ln lnsLances ln whlch Lhere ls dlrecL damage Lo endoLhellal cells whlch ln Lurn lnlLlaLe Lhe formaLlon of blood
cloLs ln Lhe damaged areas
O ellular elemenLs ln a blood vessel normally Lravel ln a sLream ln Lhe cenLre as a resulL of loss of fluld (due Lo lncreased vascular permeablllLy
and slowlng of blood flow ln vessel) Lhe cellular elemenLs(lncludlng J8s) become dlsplaced Lo Lhe perlphery of vessels where Lhey come ln
Lo conLacL wlLh Lhe endoLhellal cells marg|nat|on
O Lxudat|on process of Lhe escape of plasma and plasma proLelns along wlLh J8s from Lhe vessel accounLs for an lncrease ln Lhe volume of
lnLersLlLlal fluld (edema) and Llssue swe|||ng aL local slLe of ln[ury lnflammaLory edema ls due Lo lncreased permeablllLy
O Lxudate formed ln lnflammaLlon because vascular permeablllLy lncreases as a resulL of lncreased lnLerendoLhellal spaces whaL goes ouL
O Increased vascu|ar permeab|||ty due to
O 1 k|se |n hydrostata|c pressure wlLhln Lhe mlcroclrculaLlon arLerlolar vasodllaLlon ls followed by a rlse ln pressure wlLhln Lhe caplllarles and
venules passlve LransporL of a large volume of fluld along wlLh small molecules lnLo Lhe lnLersLlLlum evenLually lncreased permeablllLy leads
Lo movemenL of proLelnrlch fluld and cells lnLo lnLersLlLlumreduces lnLravascular osmoLlc pressure and lncreases osmoLlc pressure of Lhe
lnLersLlLlal fluld (fluld conLlnues Lo move ouL)
O 2 W|den|ng of |nterendothe||a| ce|| [unct|ons Lhese cells conLaln myoflbrlls wlLhln Lhe cyLoplasm and Lhese allow for conLracLlon of Lhe
cells mechanlsm by whlch large molecules may escape resulLlng ln a proLelnrlch eudaLes ellcLed by hlsLamlne bradyklnln
leukoLrlneslmmedlaLe LranslenL response slower more prolonged reLracLlon of endoLhellal cells due Lo changes ln cyLoskeleLon vla cyLoklnes
O 3 Lndothe||a| |n[urylmmedlaLe susLalned response (damaged vessels Lhrombosed or repalred)
O 4 Leukocyte med|ated endothe||a| |n[ury
O S Increased transcytos|s
O 6 Leakage from new b|ood vesse|s
O Character|st|cs of |nf|ammatory exudates
O 1 Plgh speclflc gravlLy (greaLer Lhan 1020)
O 2 Plgh proLeln levelsgreaLer Lhan 24gms per dl
O 3 numerous cells and cell fragmenLs
O 1ransduate due Lo rlse ln hydrosLaLlc pressure reduced plasma proLelns(oncoLlc pressure) lymphaLlc obsLrucLlon or na+ reLenLlon conslsLs
of flulds slmllar Lo waLer wlLh LCJ speclflc gravlLy (1020) wlLh llLLle Lo no proLeln nor cells LransduaLes A8 nC1 assoclaLed wlLh
lnflammaLlon buL wlLh cllnlcal slLuaLlons such as heart fa||ure venous obstruct|on ma|nutr|t|on formed when f|u|d |eaks out because of
|ncreased hydrostat|c pressure or decreased osmot|c pressure pretty much [ust a watery substance
Summary vasoconsLrlcLlon (brlef neurogenlcnoL Loo lmporLanL because we can denervaLe and sLlll geL lnflammaLlon) vasodllaLaLlon (due Lo
medlaLorse hlsLamlne) lncreased blood flow (red/hoL) lncreased permeablllLy (medlaLed by chemlcalscauses lnflammaLory edema)
hemoconcenLraLlon (fluld normally 33 plasma blood becomes more concenLraLed because more fluld has lefL) LLuLA8 vn1S
O What mechan|sms are respons|b|e for the vascu|ar events (vasod||at|on and |ncreased permeab|||ty)?
* neurogen|c med|ators operaLe ln very early phases of reacLlon fleeLlng arLerlolar vasoconsLrlcLlon mechanlsms suggesLed by S|r 1homas Lew|s
and consLlLuLes Lhe flrsL parL of Lewls's Lrlple response even wlLhouL neuroconnecLors (denervaLlon) Lhe ma[or aspecLs of acuLe lnflammaLlon
occurmaln medlaLors of Lhe vascular change are chemlcal nC1 neuronal neurogenlc medlaLors have probably a secondary and less lmporLanL
role ln mammals
* chem|ca| med|ators
O A) ell uerlved vasoacLlve MedlaLors
O I) h|stam|ne ma[or medlaLor ln early phases of acuLe lnflammaLory reacLlon ma[or sourcemast ce||sublqulLous LhroughouL Lhe body and
occur ln connecLlve Llssue ofLen ad[acenL Lo blood vessels hlsLamlne ls conLalned wlLhln granules of masL cells also found ln granules of
basophlls and plaLeleLs (along wlLh heparln) shorL llved effecL when anLlgen blnds Lo anLlbody Lo form a comple lL Lhen goes onLo blnd a
recepLor on Lhe masL cell (recepLor for c of lgC)Lhls leads Lo producLlon of 2
nd
messenger whlch produces Lhe effecL when masL cells are
ln[ured or approprlaLely acLlvaLed degranulaLe degranulaLe ln response Lo
O 1 hyslcal ln[uryLrauma heaL lrradlaLlon
O 2 erLaln chemlcal agenLsLolns bee venom proLelns from neuLrophlls
O 3 lmmunologlcal processes lmmune complees fragmenLs of complemenL sysLem
O n|stam|ne has 2 ma[or funct|ons
O 1 ullaLlon of arLerloles (vasodllaLlon)
O 2 lncreased permeablllLy ln venu|es and caplllarles
O **need necrosls for lnflammaLlon cells LhaL dle need Lo be recycled
O II) arach|don|c ac|d metabo||tes derlved from cell membrane phosphollplds release of arachldonlc acld by phosphollpases (lysosomes) ls
lnduced by mechanlcal chemlcal and physlcal sLlmull end producLs prosLaglandlns (produce vasodllaLlon and lncreased permeablllLy) and
leukoLrlnes (lncrease permeablllLy and have chemoLacLlc acLlvlLy) cells dle membrane (phoshollpase degrades phosphollplds produces
arachldonlc acld whlch leads Lo 2 separaLe paLhways produclng leukoLrlenes (vla llpoygenase) and prosLaglandln (vla cyclooygenase)
corLlsone lnhlblLs paLhway from membrane Lo AAM powerful anLllnflammaLory medlaLor LhaL prevenLs producLlon of AAM CO2 lnhlblLors
ASA lbuprophen lndomeLhecln leukoLrlenes cause brochospasm LreaLed wlLh slngular
O 8) lasma uerlved vasoacLlve MedlaLorsby producLs produced by llver
O I) k|n|ns a group of plasma and Llssue proLeases whlch are acLlvaLed by acLlons of varlous cloLLlng or complemenL sysLem fragmenLs mosL
lmporLanLbradyk|n|n4 funct|ons
10

O 1 ArLerlolar dllaLlon
O 2 lncreases caplllary/venule permeablllLy
O 3 lncreased mlgraLlon of J8s Lo slLe of ln[ury (chemoLals)
O 4 roduce pa|n
O **effecLs are LranslLory and mosL lmporLanL durlng early phases of acuLe lnflammaLlon
O II) comp|ement system conslsLs of aL leasL 11 dlfferenL proLelns clrculaLlng Lhe blood ln an |nact|ve form upon acLlvaLlon of Lhe sysLem (e by
conLacL wlLh anLlgen anLlbody comple) varlous by producLs of complemenL are released some have properLy of lncreaslng vascular
permeablllLy and oLhers are responslble for aLLracLlng J8s Lo slLe of lnflammaLlon beglns wlLh 1
O III) c|ott|ng factors Lhe c|ott|ng (coagu|at|on) system forms a flbrlnous eudaLes or meshwork aL Lhe lnflamed slLe Lo 18A cells mlcro
organlsms and forelgn bodlesprevenLs spread of lnfecLlon and lnflammaLlon lnLo Lhe surroundlng Llssues keeps cell debrls bacLerla and
forelgn bodles aL Lhe slLe of greaLesL phagocyLlc acLlvlLy and forms a cloL LhaL sLops Lhe bleedlng and provldes a framework for repalr and
heallng maln subsLancef|br|nlnsoluble proLeln whlch ls Lhe end producL of Lhe coagulaLlon cascade sLarLs ln llver when you break Lhe
blood cloL you geL lnflammaLory medlaLors flbrln spllL producLs
O M|sce||aneous neuLrophll enzymes or lysozymes are llberaLed aL Lhe lnflammaLory slLe and are responslble for furLher release of medlaLors
such as hlsLamlnes klnlns eLc some of Lhese enzymes can also dlgesL organlc maLerlal cytok|nesproducLs of sLlmulaLed lymphocyLes
|nterferon and tumour necros|s factor
O PlsLamlne soon followed by klnlns lnlLlaLes early vascular phenomenon fracLlons of complemenL are also lnvolved aL an early sLage LA18
changes ln lncreased vascular permeablllLy are due Lo prosLaglandlns lysozymes and S8S (slow reacLlng subsLance of anaphylals)
Ce||u|ar Changes
O ells ln clrculaLlon 88 (8um) J8 (1020um) plaLeleLs (13um)
O normally heavler cells (J8s) Lravel ln cenLer wlLh 88s and plaLeleLs ln perlphery durlng lnflammaLlon Lhe blood geLs more vlscous due Lo
lncreased permeablllLy 88s become crowed and sLlck LogeLher (8ouleou phenomenom) Lravel ln packs (become heavler) and move Lo
cenLer pushlng J8s Lo perlpherymarg|nat|on (1)
O (2)avement|ng J8s become sLlcky and adhere Lo Lhe endoLhellum relaLed Lo Lhe presence of cell adheslve molecules on boLh endoLhellal
cells and leukocyLes J8s and endoLhellal cells have complemenLary cell adheslon molecules AMs (lnLegrlns) become overepressed durlng
lnflammaLlon due Lo chemlcal medlaLors cells begln Lo roll AMs also lmporLanL ln cell recognlLlon LransplanL re[ecLlon embryonlc
developmenL
O (3)Lm|grat|on J8s are acLlvely moLlleform pseudopods and can move ln an amebold fashlon neuLrophlls/monocyLes are Lhe mosL rapld
lymphocyLes are Lhe leasL rapld J8s Lravel along Lhe endoLhellum unLll Lhey reach Lhe wldened endoLhellal cell [uncLlon where Lhey pass
Lhrough LhaL spaceact|ve and requ|res energy 88s ofLen leave Lhe vascular lumen behlnd a J8passlve phenomenon and resulLs from
hydrosLaLlc pressure forclng 88s ouL of Lhe permeable vessel
O Neutroph||sflrsL cells Lo appear ln ln[ured Llssues (624hrs)Lhere ls many more neuLrophlls and Lhey have greaLer moLlllLy Lhen monocytes
(2448 hrs) due Lo varlous Llmlng of epresslon of AM's and release of chemlcal medlaLors aL dlfferenL phases of lnflammaLlon once ouLslde
blood vessel monocyLesmacrophages or hlsLocyLes large # of neuLrophlls aL slLe of ln[uryma[or hlsLologlcal hallmark of acuLe
lnflammaLlon afLer 23 days macrophagesneuLrophlls ln mosL lnflammaLory reacLlon slLes (**ecepLlonlnsLances ln whlch Lhe ln[urlous
sLlmulus conLlnues Lo operaLe) normal llfespan of macrophage (monLhsyears) average neuLrophll (24days) macrophages are relaLlvely
reslsLanL Lo lower pPs (acldlLy) whlch ls found aL lnflammaLory slLes
O Chemotax|s Lhe reacLlon of lnflammaLory cells Lo subsLances ln Lhelr envlronmenL deLermlnes Lhe d|rect|on of Lhelr locomoLlon Lhls
movemenL along a chemlcal gradlenLchemoLals unldlrecLlonal ln sLralghL llne as cells leave Lhe vasculaLure Lhey follow Lhe gradlenL vla
Lhelr recepLors where ln[ury occurs Lhere ls chemoLacLlc facLors LhaL aLLracL lmmune cells because Lhey have a complemenLary recepLor
O Chemotact|c factors for neutroph||s
O 1 omplemenL fracLlons
O 2 8acLerlal and vlral producLs
O 3 ollagen breakdown fragmenLs
O 4 omponenLs of Lhe klnlns sysLem
O 3 8reakdown fragmenLs of flbrln
O hagocytos|s Lhe process of lngesLlon of parLlculaLe maLLer (bacLerla forelgn debrls) by cell cell eaLlng" regarded as Lhe culmlnaLlon of an
lnflammaLory reacLlon neuLrophlls/macrophages greaLesL phagocyLlc properLles eoslnophlls are Loo nC1 lymphocyLes and plasma cells
ma|n mechan|sm for bacter|a| k||||ng and degradat|on
O orelgn maLerlal comes ln conLacL wlLh cell membrane cyLoplasm of neuLrophll or macrophage flows around Lhe parLlcle Lrapplng lL wlLhln a
sac forelgn maLerlal becomes bound by a membrane derlved from plasma mambrane lysosomes fuse Lo Lhe sack and release Lhelr
enzymes dlrecLly lnLo Lhls sack or vacuoleremalnder of debrls ls removed by lymphaLlcs
O Iactors affect|ng phagocytos|s
O A) opson|ns subsLances whlch coaL bacLerla and render Lhem more suscepLlble Lo phagocyLosls usually lmmunoglobullns or complemenL
fracLlons J8 has recepLors for lgC and complemenL facLor 3 (coaLlng maLerlal) afLer flrsL conLacL phagocyLosls beglns change shape and
surround polnL of conLacL vla conLracLlle proLelns engulf bacLerla phagocyLe vacuole fuses wlLh lysosome enzymes klll bacLerla
requlres loLs of oygen because paLhway makes loLs of hydrogen perolde
O Iate of engu|fed mater|a|
O 1 desLroyed or dlgesLed by Lhe lysosomal enzymes wlLhln Lhe neuLrophll/macrophage
O 2 1he lnflammaLory cell may be desLroyed by Lhe forelgn parLlcleparLlcularly vlrulenL bacLerla may cause deaLh of Lhe lngesLlng cell
11

O 3 Crganlsms may survlve for some Llme wlLhln Lhe macrophagese Luberculosls remalns vlable wlLhln macrophages for many monLhs or
even years and movemenL of Lhe macrophage Lhrough Lhe lymphaLlcs Lo Lhe lymph nodes acLually resulLs ln Lhe spread of lnfecLlon
ardlnal Slgns of lnflammaLlon and Lhelr aLhogens
1 8edness (rubor)dllaLlon and congesLlon of blood vessels
2 Swelllng (Lumor)eudaLlon of fluld (lncreased vascular permeablllLy) and cells
3 PeaL (calor)mechanlsms are poorly undersLood greaLer blood flow may be conLrlbuLlng facLor
O **above Lhree are a resulL of vascular changes and cell recrulLmenL
4 aln (dolor)pressure upon nerves by Lhe edema fluld dlrecL effecL of bradyk|n|ns and prostag|and|ns
3 Loss of funcLlonsecondary Lo refle lnhlblLlon of muscular movemenLs assoclaLed wlLh paln mechanlcal dlsablllLy may be produced by swelllng
and paln
O **above Lwo are a resulL of medlaLor elaboraLlon and leukocyLemedlaLed damage
lasslflcaLlon of lnflammaLlon
O lasslfled accordlng Lo Lhe 1 uuraLlon (mosL lmporLanL) 2 1ype of eudaLe formed (morphologlcal paLLern) 3 LocaLlon and speclal forms
O 1 1ype of |nf|ammat|on based on durat|onaccord|ng to durat|on and h|sto|ogy
O AcuLe or chronlc no sharp llne of dlvlslon elsLs beLween Lhese forms
O Acute ln a c||n|ca| sense lL ls usually of sudden onseL and accompanled by one or more of Lhe cardlnal slgns generally lasLs a maLLer of hours
Lo days occur when Lhe ln[ury ls LranslenL (physlcal Lrauma burn lnfecLlon whlch ls qulckly eradlcaLed chemlcal agenLs Llssue necrosls
forelgn bodles lmmune reacLlon) patho|og|ca| sense has lLs domlnanL morphologlcal changes as Lhe vascular and eudaLlve changes
descrlbed above (eudaLlon of fluld and accumulaLlon of cells shorL llved marked vascular effecLs (vasodllaLaLlon and lncreased permeablllLy)
cellular lnfllLraLe conLalns numerous neuLrophllsbecause we have Lhe mosL of Lhese cells and Lhese are Lhe fasLesL) acute |nf|ammat|on
"exudat|ve |nf|ammat|on" because |ots of stuff |eaves ex append|c|t|s
O Chron|c |nf|ammat|on resulLs from an ln[urlous agenL whlch perslsLs ln Lhe Llssues and conLlnues Lo cause damage (forelgn body LhaL
remalns organlsms LhaL are noL eradlcaLed) pro||ferat|on and hea||ng may follow acuLe or may be chronlc from onseL may be nonspeclflc
may be granulomaLous (glanL cells) may geL scarrlng (slgn of heallng) e ArLhrlLls loflox of lympbocytes ooJ moctopboqes octlve
loflommotloo tlssoe lojoty ooJ beolloq ptoceeJ slmoltooeoosly chorocterited by lofllttotloo wltb mooooocleot cells tlssoe Jesttoctloo tepolt
lovolvloq oew vessel ptollfetotloo (ooqloqeoesls) ooJ flbtosls can arlse from 2 dlfferenL seLs of clrcumsLances
O A) evo|ut|on of acute to chron|c |nf|ammat|on occurs characLerlsLlcally ln cerLaln lnfecLlons as agenL perslsLs ln Llssue so does Lhe
lnflammaLory reacLlon e SLaphylococcal lnfecLlon of bone (osLeomyellLls) flrsLLyplcal changes assoclaLed wlLh acuLe lnflammaLory reacLlon
Lhen Lhere ls a mass of bone LhaL becomes necroLlc and a sulLable place for bacLerla Lo llve Lhls area ls very dlfflculL for body's defences Lo
reach dlfflculL for anLlbloLlcs Lo reach bacLerla ln necroLlc Llssue lasLs for weeks Lo years lnflammaLory reacLlon wlLh chronlclLy Lakes on 2
faceLs
O I) a prollferaLlon of connect|ve t|ssue (predomlnanLly flbroblasLs) and vesse|s (anglogenesls)
O II) local lncrease ln macrophages lymphocyLes and plasma cells
O **no Llme clearly separaLes acuLe from chronlc dlfferenLlaLlon resLs upon cllnlcal and morphologlcal paLLern
O 8) chron|c |nf|ammat|on w|thout any recogn|zab|e acute phase occurs wlLh low grade ln[urles (organlsms of relaLlvely low vlrulence or
auLolmmune dlseases) e lnflammaLory reacLlon Lo Lhe Lubercle baclllus (Luberculosls) whlch rapldly passes Lhrough an acuLe paLLern
O hronlc lnflammaLory paLLern mononuclear cell lnfllLraLe connecLlve Llssue responsenon speclflc paLLern
O Granu|omatous |nf|ammat|on speclal form of chronlc lnflammaLlon characLerlsLlc response seen ln some lnfecLlons (tubercu|os|s
syphlllsleprosy caLscraLch dlsease sarcroldosls crohn dlsease fungl forelgn body) characLerlzed by presence of granulomas (gralnllke
noodles)well clrcumscrlbed collecLlon of eplLhellod macrophages (resemble eplLhellal cellsabundanL eoslnophlllc cyLoplasm) wlLh rlm of
lymphocyLes and plasma cells may or may noL be a cenLral focus of necroLlc debrls (promlnenL ln Luberculosls) ofLen mulLlnucleaLed glanL
cells (made of macrophages) are presenL and are helpful ln recognlzlng a granuloma g|ant ce||s represenL eplLhellod macrophages whlch have
fused Lhelr cell borders resulLlng ln one large mulLlnucleaLed cellofLen form around forelgn bodles when forelgn parLlcles are Loo large Lo be
engulfed by a slngle macrophage an ouLer rlm of lymphocyLes and plasma cells ls frequenLly seen around many granulomas
O Chron|c |nf|ammat|on ar|ses perslsLenL lnfecLlons by mlcrobes LhaL are dlfflculL Lo eradlcaLe lmmune medlaLed lnflammaLory dlseases
(hypersenslLlvlLy) prolonged eposure Lo poLenLlally Lolc agenLs
O 2 1ypes of |nfect|on based on exudatesmorpho|og|ca| patterns of acute and chron|c |nf|ammat|on based on predom|nant|y the type of
exudates
O ln order of |ncreas|ng sever|ty (|east severe to most)
O Serous fluld conLalns mosLly albumln (no flbrlnogen) derlved from secreLlons of serosal surfaces (pleural perlLoneal perlcardlal synovlal)
proLeln poor e skln bllsLer fluld ln serous cavlLyeffuslon e burns asclLls pleurLlLls dlfflculL Lo see ln Llssues noL many cells and proLelns
elLlng
O I|br|nous characLerlzed by presence of flbrln (derlved from leakage of flbrlnogen from blood vessels) seen ln more severe lnflammaLlons
where Lhere ls a greaLer degree of lncreased vascular permeablllLyallows large proLeln molecules (flbrlnogen) Lo pass Lhrough appears as
eoslnophlllc meshwork of Lhreads or an amporphous coagulum lnflammaLlon ln llnlng of cavlLles (menlnges perlcardlum pleura) e rhemaLlc
fever pneumococcal pneumonla bread and buLLer"
O Suppurat|ve or puru|ent when large amounLs of pus (fluld conLalnlng neuLrophlls and llquefled Llssue debrls and bacLerla) are made seen ln
cerLaln lnfecLlons such as sLaphylococcl llquefacLlve necrosls by bacLerla pus puswhlLe necroLlc Llssue/cells wlLh neuLrophlls (enzymes)
O Catarra| assoclaLed wlLh ouLpourlng of large amounL of mucus seen ln Lhe course of lnflammaLlon of mucoussecreLlng membranes
(common coldvlral lnfecLlon Lo resplraLory eplLhellum of nose)
O Sangu|neous Lhe eudaLes conLalns large number of 88slndlcaLlve of serlous damage Lo blood vessels mosL severe rupLure of vessels
(haemorrhage) Luberculous pleurlLls e frosL blLe lce crysLals form ln blood vessel and puncLure lL
12

O **eudaLes are very lnfrequenLly pure usually a comblnaLlon of several Lypes
O 3 Locat|on and spec|a| forms
O Abscess locallzed collecLlon of pus ln Llssue or organ Lyplcally have a cenLral largely necroLlc reglon rlmmed wlLh layer of preserved
neuLrophlls wlLh a surroundlng layer of dllaLed vessels and flbroblasLlc prollferaLlon well conflned
O Ce||u||t|sdlffuse lnflammaLlon LhaL spreads deep wlLhln solld Llssue e beLa haemolyLlc sLrepLococcal lnfecLlon of skln
O Carbunc|e abscess of subcuLaneous Llssue wlll evenLually draln Lo Lhe surface
O Lmpyema collecLlon of pus ln a preformed cavlLy usually pleural cavlLy
O U|cer local defecL or ecavaLlon of Lhe surface of an organ or surface covered ln an eplLhellum mucous membrane skln mouLh sLomach
lnLesLlnes or ln clrculaLory dlsLurbances produced by necrosls of cells and sloughlng of lnflammaLory necroLlc Llssue musL elsL near surface
removed/desLroys eplLhellum
O seudomembranous occurs on mucosal surfaces e resplraLory passages (dlphLherla) Cl LracL characLerlzed by accumulaLlon of flbrln
necroLlc debrls and acuLe lnflammaLory cells on Lhe surface eudaLe ls on Lop llke a cap/membrane conLlnuous admlnlsLraLlon of anLlbloLlc
maln cause
O I|stu|a abnormal communlcaLlon beLween Lwo hollow organs boLh llned wlLh eplLhellum (e veslcouLerlne beLween urlnary bladder and
uLerus) or endoLhellum (e arLerlovenous) may be congenlLal or may resulL from a neoplasm or Lrauma connecLs Lhlngs LhaL shouldn'L be
connecLed
O S|nus abnormal LracL (communlcaLlon) beLween a solld organ and an eplLhellal covered surface usually skln (e pulmonary abscess whlch
dralns Lo Lhe skln's surface) e muscle and skln
O aronych|alnflammaLlon around nall e lf you have lL ln waLer for Loo long
SysLemlc effecLs of lnflammaLlonln severe lnflammaLory reacLlons
1 Iever resulL of release of facLors from Lhe J8s or from mlcroorganlsms (pyrogens) LhaL acL dlrecLly on Lhe LemperaLure regulaLlng cenLre ln Lhe
hypoLhalamus
2 Leucocytos|s lncrease ln Lhe J8 counL above normal levels (10000/mm) lncreased producLlon and release of J8 from and by Lhe bone
marrow acute |nf|ammatory response leukocyLosls ls Lhe resulL generally of an lncreased number of neuLrophlls (one wlll also see an lncreased
number of lmmaLure neuLrophlls ln blood) ln chron|c |nf|ammatory response more llkely Lo have a lymphocyLosls (absoluLe lncreases ln numbers
of lymphocyLes) a||erg|c react|on eoslnophllla frequenLly seen
3 Cther malalse anorela sleeplness elevaLed levels of acuLe phase proLelns (creacLlve proLeln flbrlnogen serum amylold) lncreased P8 and
blood pressure chllls decreased sweaLlng sepLlc shock (fall ln 8 dlssemlnaLed lnLravascular coagulaLlon meLabollc abnormallLles lnduced by
hlgh levels of 1n)
1eLbook MaLerlal
O lnflammaLlon a proLecLlve response lnLended Lo ellmlnaLe Lhe lnlLlal cause of cell ln[ury as well as Lhe necroLlc cells and Llssues resulLlng from
Lhe orlglnal lnsulL
O ulluLes desLroys or neuLrallzes harmful agenLs
O arL of lnnaLe lmmunlLy
O AlLhough lnflammaLlon helps clear lnfecLlons and oLher nolous sLlmull and lnlLlaLes repalr Lhe lnflammaLory reacLlon and Lhe subsequenL
repalr process can cause conslderable harm
O SLeps of lnflammaLory response (3 8's) 1 8ecognlLlon of Lhe ln[urlous agenL 2 8ecrulLmenL of leukocyLes 3 8emoval of agenL 4 8egulaLlon
(conLrol) of Lhe response 3 8esoluLlon (repalr)
O Loss of proLeln rlch fluld lnLo perlvascular space lncreases osmoLlc pressure of lnLersLlLlal fluld neL resulL ouLflow of waLer and lons lnLo
eLravascular Llssues
O ln lnflammaLlon lymph flow ls lncreased and helps draln edema fluld from Lhe eLravascular space lymphaLlc fluld equlllbraLes wlLh
eLravascular fluld lymphaLlcs may become secondarlly lnflamed and Lhe lymph nodes(hyperplasla of lymphold folllcles
O LeukocyLe recrulLmenL 1 MarglnaLlon adheslon Lo endoLhellum and rolllng along vessel wall (medlaLed by selecLln and L selecLln blnd
slalylLewls on leukocyLes) 2 lrm adheslon Lo Lhe endoLhellum (medlaLed by lnLegrlns epressed on leukocyLe cell surface lnLeracLlng wlLh
Lhelr llgands on endoLhellal cells acLlvaLed by chemoklnes) 3 1ransmlgraLlon beLween endoLhellal cells (dlapedeslsmovemenL Lhrough
lnLracellular [uncLlons ln venules) 4 MlgraLlon ln lnLersLlLlal Llssues Loward a chemoLacLlc sLlmulus (cross vascular basemenL membranes by
focally degradlng Lhem wlLh secreLed collagenases
O hemoLacLlc agenLs for leukocyLes bacLerlal producLs (nformylmeLhlonlnle Lermlnl) cyLoklnes componenLs of Lhe complemenL sysLem (3a)
and producLs of Lhe llpoygenase paLhway of arachldonlc acld
O 8ecepLors of chemoklnes Ccoupled proLeln recepLor
O LeukocyLes move by eLendlng pseudopods dlrecLlon of movemenL speclfled by a hlgher denslLy of recepLorchemoLacLlc llgand lnLeracLlon aL
Lhe leadlng edge of Lhe cell
O 1n and lL1 promoLe epresslon of selecLlns and lnLegrln llnads on endoLhellum
O LeukocyLe recepLors
O 1L8 recognlze endoLolns (LS) and oLher bacLerlal and vlral producLs
O C8 recognlze cerLaln bacLerlal pepLldes and medlaLors
13

O LeukocyLe acLlvaLlon resulLs ln phagocyLosls of parLlcles producLlon of subsLances LhaL desLroy phagocyLosed mlcrobes and remove dead
Llssues (lysosomal enzymes 8CS) producLlon of medlaLors LhaL ampllfy Lhe lnflammaLory reacLlon (arachldonlc acld meLabollLes and
cyLoklnes)
O Cx|dat|ve burst Lrlggered by phagocyLosls sudden lncrease ln C2 consumpLlon glycogen caLabollsm lncreased glucose oldaLlon and
producLlon of 8CS
O L|astasemosL lmporLanL lysosomal enzyme lnvolved ln bacLerlal kllllng
O k||||ng agents 8CS enzymes bacLerlcldal permablllLylncreaslng proLeln lysozyme ma[or baslc proLeln defenslns (creaLe holes)
O LeukocyLe dependenL Llssue ln[ury underlles many acuLe and chronlc human dlseases
O AcLlvaLed leukocyLes especlally macrophages secreLe many cyLoklnes
O LeukocyLes can ellmlnaLe mlcrobes and dead cells by phagocyLosls followed by Lhelr desLrucLlon ln phagolysosomes desLrucLlon ls caused
by free radlcals generaLed ln acLlvaLed leukocyLes and lysosomal enzymesenzymes and 8CS may be released lnLo Lhe eLracellular
envlronmenL mechanlsms LhaL funcLlon Lo ellmlnaLe mlcrobes and dead cells (physlologlc role of lnflammaLlon) are also capable of
damaglng normal Llssues (paLhologlcal consequences)
O uefecLs ln leukocyLe funcLlon defecLs ln leukocyLe adheslon defecLs ln mlcroblcldal acLlvlLy (chronlc granulomaLous dlsease) defecLs ln
phagolysosome formaLlon (hedlakPlgashl syndrome)
O CuLcomes of acuLe lnflammaLlon 1 resoluLlon (clearance of ln[urlous sLlmull clearance of medlaLors and acuLe lnflammaLory cells
replacemenL of ln[ured cells normal funcLlon) 2 rogresslon Lo chronlc lnflammaLlon (anglogensls mononuclear cell lnfllLraLe flbrosls scar)
3 Scarrlng or flbrosls (usual ouLcome of abscess formaLlon ls scarrlng loss of funcLlon)
O MedlaLors may be produced locally by cells aL Lhe slLe of lnflammaLlon or Lhey may be clrculaLlng ln Lhe plasma as lnacLlve precursors mosL
medlaLors lnduce Lhelr effecLs by blndlng Lo speclflc recepLors on LargeL cells medlaLors may sLlmulaLe LargeL cells Lo release secondary
effecLor molecules Lhe acLlons of mosL medlaLors are LlghLly regulaLed
O Macrophages masL cells endoLhellal cells aL slLe of lnflammaLlon leukocyLes recrulLed Lo slLe from bloodcapable of produclng dlfferenL
medlaLors of lnflammaLlon
O ell derlved hlsLamlne and seroLonln (preformed medlaLors ln secreLory granules) prosLaglandlns leukoLrlenes plaLeleL acLlvaLlng facLor
8CS nC cyLoklnes neuropepLldes (newly synLheslzed) vasoacLlve amlneshlsLamlne seroLonln vasodllaLlon and lncreased vascular
permeablllLy arachldonlc acld meLabollLes prosLaglandlns and leukoLrlenes vascular reacLlons leukocyLe chemoLals (anLagonlzed by
llpolns) cyLoklnesleukocyLe recrulLmenL and mlgraLlon (1n and lL1) 8CSmlcrobrlal kllllng Llssue ln[ury nC vasodllaLlon mlcroblal
kllllng lysosomal enzymesroles ln mlcroblal kllllng Llssue ln[ury
O lasma proLeln derlvedproduced ln llver complemenL acLlvaLlon (3a 3a 3b) and facLor Oll acLlvaLlon (klnln sysLem
coagulaLlon/flbrlnolysls) complemenL proLelns acLlvaLed by mlcrobes or anLlbodles leads Lo Lhe generaLlon of mulLlple breakdown producLs
whlch are responslble for leukocyLe chemoLals opsonlsaLlon and phagocyLosls of mlcrobes and oLher parLlcles and cell kllllng coagulaLlon
proLelns acLlvaLed facLor Oll Lrlggers Lhe cloLLlng klnln and complemenL cascades and acLlvaLes Lhe flbrlnolyLlc sysLem klnlns produced by
proLeolyLlc cleavage of precursors medlaLe vascular reacLlon and resulL ln paln
O yLoklnes 1n and lL1 effecL on endoLhellal sysLemlc flbroblasL leukocyLe lnduce sysLemlc acuLe phase reacLlon
O 8CS synLheslzed vla nAuP oldase paLhwayreleased from neuLrophlls and macrophages
O Macrophages secreLe acld and neuLral proLeases 8CS and nC AA meLabollLes cyLoklnes
O Macrophages dlsplay anLlgens Lo 1cells epress membrane molecules and produce cyLoklnes LhaL sLlmulaLe 1 cell responses (lL12)
O AcLlvaLed 1 cell produces cyLoklnes (lny) acLlvaLor of macrophages
O AlLhough neuLrophlls are Lhe classlc hallmarks of acuLe lnflammaLlon many forms of chronlc lnflammaLlon may neverLheless conLlnue Lo show
neuLrophllc lnfllLraLes
O 1n lL1 and lL6 medlaLors of acuLe phase reacLlon
O neuLrophllla lncrease ln blood neuLrophlls
O Leukopenla decreased number of J8S
8ole of LymphaLlcs and Lymph nodes
O llLers and pollces eLravascular flulds
O Cpens durlng lnflammaLlon edema
O uraln fluld cells and cell debrls
O ln some cases lymphanglLls (lnfecLlon of lymph vessel) and lymphadenLls(lnfecLlon of lymph node)
O lrsL sLop lymph node clrculaLlon
uefecLs of leukocyLe funcLlon LhaL affecL lnflammaLlon
O ln #'s ln adherence ln mlgraLlon (lnLrlnslc/eLrlnslc) ln phagocyLosls ln mlcroblocldal acLlvlLy mled effecLs
8egeneraLlon and 8epalr
lnLroducLlon
O 1lssues are resLored (Lo sLrucLural and funcLlonal lnLegrlLy) vla
O 8emoval of eudaLe
O 8emoval of cellular and Llssue debrls
O 8eplacemenL of cells and Llssues losL
14

*sLable only dlvlde lf kllled/damaged
8eplacemenL of ells and 1lssues
O A) regenerat|on lf Lhe cells (or Llssue) replaclng Lhose losL ln lnflammaLlon are |dent|ca| or very slmllar (physlologlcal or paLhologlcal)
O 8) repa|r a broader Lerm lL lncludes Lhe process of replacemenL by cells and Llssues elLher of Lhe same klnd as Lhose losL or of a dlfferenL and
ofLen slmpler Lype paLhologlcal
O ells of Lhe body are dlvlded lnLo 3 groups on Lhe basls of Lhelr regeneraLlon capaclLy
O Lab||e conLlnue Lo prollferaLe LhroughouL llfe (eplLhellumskln bronchlal epl bone marrow epl blood cells endomeLrlal cells) follow cell
cycle from one mlLosls Lo Lhe neL Lhese Llssues can readlly regeneraLe afLer ln[ury as long as Lhe pool of sLem cells ls preserved conLaln sLem
cells LhaL dlfferenLlaLe and replenlsh losL cells and malnLaln Llssue homeosLasls
O Stab|e low normal level of repllcaLlon buL able Lo dlvlde ln response Lo sLlmull (parenchymal cells of g|andu|ar organs mesenchymal cells
endoLhellal cells flbroblasLs and smooLh muscle cells eLc) consldered Lo be on C0 buL recrulLed Lo C1 mlnlmal repllcaLlve acLlvlLy ln Lhelr
normal sLaLe e renal Lubular cells llver cells
O ermanent cannoL dlvlde ln posLnaLal llfe (neurons of nS and cardlac muscle cells) have lefL Lhe cell cycle consldered Lo be Lermlnally
dlfferenLlaLed and nonprollferaLlve ln posL naLal llfe cannoL be replaced Lhemselves
O **mosL common regeneraLlon and repalr combo ldenLlcal cells and granulaLlon Llssue
8egeneraLlon
O Much beLLer developed ln lower anlmals and ln proLozoa and meLazoan represenL Lhe ma[or feaLure of reacLlon Lo ln[ury
O hys|o|og|ca| regenerat|on (replacemenL) ln man
O pldermls blood uLerlne mucosa glandular eplLhellum
O CreaL varlaLlon ln the ab|||ty of d|fferent k|nds of ce||s and t|ssues to regenerate
O SupporLlng Llssue regeneraLes besL (flbrous osseous carLllage blood vessels eplLhellum epldermls renal Lubular glandular lnLesLlnal
uLerlne)
O CLher cells lose Lhelr ablllLy Lo regeneraLe ln posLnaLal llfe (cardlac muscle nerve) requlre replacemenL by slmpler Llssue
O Atyp|ca| regenerat|on of an organdon'L arrange properly buL are capable of dlvldlng
O ln an organ resLoraLlon depends noL only upon Lhe parenchymaLous Llssue's ablllLy Lo regeneraLe buL also wheLher or noL Lhe framework was
destroyed ( eg ln Lhe skln no sweaL + sebaceous glands or halr ln llver when archlLecLural skeleLon desLroyed regeneraLlon ls lrregular
produclng an afuncLlonal Llssue c|rrhos|s) occurs when supporL frame ls desLroyed loLs of cells buL no communlcaLlon funcLlon ls lmpalred
e hepaLlsls kllls llver cells by desLroylng framework hepaLocyLes are sLable and Lherefore replace Lhemselves buL don'L arrange properly
Lherefore noL a funcLlonal llver
O kegenerat|on of organs |n mamma|s
O Llver and lung besL also kldney and spleen (accessory splenlc Llssue)
8epalr (by connecLlve Llssue and granulaLlve Llssue)
O May begln shorLly afLer ln[ury and overlap Lhe vascular and cellular phenomena of lnflammaLlon
Mechanlsms lnvolved ln regeneraLlon and repalr
O **cruclal LhaL you have boLh conLrol of cell prollferaLlon and collagenlsaLlon and acqulslLlon of wound sLrengLh (glves sLrengLh vla collagen
becomes scar Llssue)

O A) contro| of ce|| pro||ferat|on
O Lablle cellsfollow cell cycle from one mlLosls Lo Lhe neL permanenL cells have lefL Lhe cell cycle and are desLlned Lo senesce and dle sLable
cells besL consldered ln Lhe C0 buL are able Lo be sLlmulaLed Lo C1
O ArresL aL C2 before enLerlng mlLosls resulLs ln appearance of polyploldy cells (hyperLrophy)
O CrowLh ls besL accompllshed by recrulLmenL of C0 cells ln1C Lhe cell cycle Lakes place by acLlon of
O growLh or sLlmulaLory facLors some always presenL( CP sL lnsulln rog) and some are produced ln area of ln[ury (C C CLurn on
mlLosls)
O loss of a growLh lnhlblLor normally presenL (negaLlve feedback)
O ellcell or cellmaLrl lnLeracLlons conLacL lnhlblLlon lnLegrlns flbronecLlon AMSknow when Lhey have Lhe rlghL denslLy and know
when Lo sLop dlvldlng
O **all 3 are probably ln effecL aL a glven Llme
O an'L heal paper cuL wlLhouL AMs on leukocyLes
O Peallng ls faclllLaLed by lnflammaLlon
St|mu|atory hormones and growth factors
O Jellknown hormones esLrogens progesLerone somaLoLropln lnsulln
O olypepLlde growLh facLors epldermal growLh facLor flbroblasL growLh facLor plaLeleL derlved growLh facLor vascular endoLhellal growLh
facLor lnLerleuklns l and ll (lymphocyLe prollferaLlng facLors) 1n Lumourlnduced growLh facLors (sarcoma growLh facLor) nerve growLh
facLors macrophage derlved growLh facLors essent|a||y they are a|| m|togen|c
Ce||ce|| |nteract|ons
O essaLlon of prollferaLlon ln Llssue culLures due Lo conLacL lnhlblLlon" also known as denslLy dependenL
Ce||matr|x |nteract|ons
O ells have recepLors LhaL recognlze eLracellular maLrl Lhese recepLors (Lransmembrane glyocoproLelns) lnLeracL wlLh cell cyLoskeleLon one
group of such recepLors ls lnLegrlns"parL of a large famlly and lnclude
O lbronecLln recepLor plaLeleL surface recepLors leukocyLe adheslon molecules
13

O lnLegrlns recognlze a speclflc AA sequence
Lxtrace||u|ar Matr|x collagens glycosamlnoglycans proLeoglycans glycoproLelns and mosL lmporLanL f|bronect|ns (PMJ glycoproLelns) flbronecLlns
adhere Lo cell and llnks cell Lo collagen neLworkacLs as brldge (adheslve maLrl proLeln)
I|bronect|ns (||ke crazy g|ue) seen ln
O ell surfaces basemenL membranes and perlcellular maLrlces
O Are produced by flbroblasLs(also produce collage) endoLhellal cells monocyLes
O ln wound heallng flbronecLlns faclllLaLe mlgraLlon of eplLhellum (gluellke) are chemoLacLlc for monocyLes and flbroblasLs sLlmulaLe
endoLhellal mlgraLlon and organlzaLlon release bC(flbroblasL growLh facLor) from monocyLes
8) Co||agen|zat|on and Wound Strength (repa|r by connect|ve t|ssue)
O lnvolves Lhe prollferaLlon of endoLhellal cells flbroblasLs and Lhe deposlLlon of collagen ln wounds
O Severe or perslsLenL ln[ury damage of parenchymal cells and sLromal framework heallng cannoL occur by regeneraLlon along non
regeneraLed parenchymal cells are lnlLlally replaced by prollferaLlng flbroblasLs and endoLhellal cells by 33 days granulaLlon Llssue ls
esLabllshed
O CranulaLlon Llssue caplllarles blood vessels collagen M lnflammaLory cells lnlLlal replacemenL
O Granu|at|on t|ssue plnk sofL granular and palnless mesh of caplllarles flbroblasLs lnflammaLory cells and M acLs llke a scaffold on whlch
Lhe flnal scar wlll form wlLh Llme Lhe cells wlll dlmlnlsh Lhe caplllarles wlll dlsappear and lncreaslng amounL of connecLlve Llssues(collagen
scar) wlll be lald down no longer need nuLrlLlon from blood vessels once you heal you don'L need vessels anymore replaced by collagen
SLeps of 8epalr rocess
1 Anglogensls new vessels from buddlng of preelsLlng vessels newly formed vessels are lmmaLure and Lherefore leaky (lncompleLely formed
lnLracellular [uncLlons) Lhus Lhe edemaLous appearance chemlcal medlaLors responslble vC (vascular endoLhellal growLh facLor) and b
C blnd Lo Lhe proLeoglycans of Lhe basemenL membrane and are released when Lhey are damaged
2 lbrosls by prollferaLlon of slLe flbroblasLs and deposlLlon of M by Lhese cells dependenL on varlous growLh facLors released by
lnflammaLory cells
3 MaLuraLlon and organlzaLlon of Lhe scar (remodelllng) collagen and oLher M are degraded by a famlly of meLalloproLelnases (zlnc
dependenL) cleave flbrlllar collagen Lypes l ll lll lv and flbronecLln produced by lnflammaLory cells and by some eplLhellal cells ald ln Lhe
debrldemenL of Lhe ln[ured slLe and Lhe remodelllng of connecLlve Llssue lnLernal debrldemenL
ollagen
O MosL common proLeln ln anlmal world
O amlly of molecules (18 Lypes)
O 3 ma[or Lypes of collagen accordlng Lo blochemlcal composlLlon
O l ll and ll flbrlllary
O lv and v amorphous
O 8asemenL membrane componenLs Lypes lv and v collagen lamlnln flbronecLln and heparln sulphaLe proLeoglycan
O Scar Lype lll collagen Lype l collagen
O 1ype lll lmmaLure granulaLlon Llssue
O 1ype l mosL common fully maLure adulL skln
ulgesLlon of ollagen flbres
O ollagenases (produced by flbroblasLs macrophages Mn synovlal cells some eplLhellal cells) and meLalloproLelns
CLher Lracellular onnecLlve 1lssue omponenLs
O 1 lasLlc lbers
O roduced by flbroblasLs
O 1wo componenLs elasLln (amorphous) and elasLlc mlcroflbrll (flbrlllary)
O Lremely long half llfe
O ulgesLed by elasLases (bacLerla Mn macrophages)
O 2 Lamlnln
O Large glycoproLeln
O omponenL of basemenL membrane
O MedlaLes aLLachmenL of eplLhellal cells Lo Lype lv collagen
O 3 Clycosamlnoglycans and proLeoglycans
O osslbly requlred for orlenLaLlon of collagen flbers
O 4 lbronecLln
O Large glycoproLeln
O AssoclaLed wlLh cell surfaces basemenL membrane maLrl
O roduced by flbroblasLs monocyLes endoLhellal cells
O ln blood ls a cyroglobulln
O Invo|ved |n |nteract|ons of ce||s and matr|x
O unknown mechanlsms whlch lnlLlaLe and LermlnaLe secreLlon probably lnLeracLlon beLween cells and local facLors
Wound strength wounds lnvolvlng skln fascla or Lendon never regaln lnlLlal sLrengLh of Llssue derlved 708 of Lenslle sLrengLh achleved aL 3
monLhs) why? robably relaLed Lo Lype of collagen lald and lLs organlzaLlon nv8 back Lo 100 lmpllcaLlons for aLhleLes collagen lllcollagen l
glves sLrengLh
O AdulL sklncollagen Lype l
16

O CranulaLlon Llssuecollagen Lype lll
O lcaLrlsaLlonreplacemenL of Lype lll by Lype l
Sk|n Wound nea||ng
a) kepa|r of sk|n wounds
O l)repalr of dermal woundsrepalr process slmllar evenLs Lake place ln Lhe heallng of ulcers repalr ln Luberculous cavlLles of lung repalr of
abscesses ln llver and kldneys followlng Lrauma by mlsslles
O ll) crust format|on provldes a qulck provlslonal closure(scab) Lo Lhe wound
O AfLer hemorrhage has ceased Lhe wound ls covered by coagulaLed blood whlch drles and hardenscrusL(drled up bloodacLs as cork glves
message Lo boLh sldes and Lell Lhem Lo dlvlde) or scab useful ln 2 ways
O lL sLops furLher leaklng of blood and lL ls a barrler Lo lnfecLlon
O 1he crusL effecLs a provlslonal closure of Lhe wound only formed lf
O 8lood ls avallable (vessels presenL and damaged) and condlLlons permlL drylng
O **no crusL formaLlon ln cornea and uLerlne mucosawhy?
O lll) remova| of dead t|ssue other debr|s and exudatess|ough|ng and phagocytos|s
O ollowlng ln[ury large mass of dead Llssue remalns ln conLacL wlLh llvlng parLs dead Llssue may be removed by sloughlng (falllng off) Lhe
lnflammaLory response of Lhe surroundlng llvlng Llssue lnlLlaLes Lhe process of repalr a llne of zone of demarcat|on belng formed slough
loses conLlnulLy wlLh llvlng Llssue lncrease collagen
O Small amounLs of dead Llssue debrls and eudaLes are removed by llquefacLlon and phagocyLosls and by lymphaLlcs
O lv) rep|acement of |ost ce||s and t|ssues
O 1akes place by 2 processes
O ell mlgraLlon and cell dlvlslon (prollferaLlon)
O ells swell and reassume embryonal properLles
O ln skln wounds 3 klnds of cells prollferaLe and mlgraLe
lbroblasLs (mlgraLe aL 8 mlcra/hour) endoLhellum (mlgraLe ln arcs and afLer a lag perlodanglogenesls) eplLhellum (mlgraLes ln sheeLs)
ulrecLlon of flbers formed ls deLermlned by Llssue Lenslon
CranulaLlon Llssue and eplLhellal regeneraLlon lncrease collagen and decrease blood vessels
O new Llssue conLalnlng prollferaLlng cellular and eLracellular componenLs ls formed Lo replace Lhe loss granu|at|on t|ssue because Lo Lhe
naked eye lL appears as an aggregaLlon of plnk granules conslsL of
O newly formed caplllary flbroblasLs elaboraLlng connecLlve Llssue (eLracellular) many macrophages
O CranulaLlon Llssue has Lhe followlng properLles
O 8leeds freely lnsenslLlve Lo paln (no nerves) qulLe reslsLanL Lo lnfecLlons
O Lp|the||um ln order Lo mlgraLe (ln sheeLs) lL requlres a subsLraLum (granulaLlon Llssue/flbronecLln) no defecL ln underlylng
mesenchymelmmedlaLe mlgraLlon (ln cornea compleLlon ln 6hrs) ln larger wounds lL passes beLween Lhe scab and Lhe granulaLlon Llssue
and Lhe scab drops off
O C|catr|sat|on converslon of granulaLlon Llssue Lo scar (gradual closlng of small vessels) process of scarrlng may be ln any Llssue
O Adhes|ons may form ln repalr followlng ln[ury and lnflammaLlon of serous membranes (flbrous connecLlons" beLween 2 serosal surfaces) e
afLer abdomlnal surgery
O ke|o|d(overproduct|on of scar t|ssue too much co||agen) a posL LraumaLlc repalr/connecLlve Llssue prollferaLlon ln Lhe dermls LhaL eceeds
above and beyond" Lhe amounLs necessary gross|y red (or plgmenLed) ralsed and flrm leslon wlLh sharp ofLen lrregular ouLllne and a
smooLh shlny surface m|croscop|ca||y epldermls and Lhe sub[acenL dermls are nC8MAL buL Lhere are no skln appendages acLual leslon
conslsLs of lrregularly arranged broad homogenous hyallnlsed and aL Llmes basophlllc collagen flbres moderaLe lncreased ln Lhe # of
flbroblasLs and caplllarles boLh dlsappear" ln an aglng" leslon 10 of normal people develop kelold scars
O 1hlck dermls wlLh randomly arranged collagen
O Cccurs more ofLen ln dark sklnned people
O 8) pr|mary repa|r or pr|mary un|on or f|rst |ntent|on
O 1he Lype of repalr LhaL follows when Lhe edges of Lhe wound are ln apposlLlon may be Lhe case when lL mlmlcs closely resLlLuLlon ad
lnLegrum 2 edges of Lhe wound are close LogeLher
O Jound ls superflclal lnvolvlng only Lhe epldermls and Lhe dermls remalns lnLacL no bleedlng repalr Lakes place vla regeneraLlon of Lhe
eplLhellum Lhe eplLhellal cells mlgraLe across Lhe cuL and may replace lL ln one day
O ueeper cuL lnLo dermls wlLh a few caplllarles cuL few drops of blood whlch cemenL" Lhe edges of Lhe wound Lhus no wound reLracLlon a
few flbroblasLs and endoLhellal cells mlgraLe pracLlcally no or very small scar
O ln deeper cuLs when reLracLlon presenL surgeon may approlmaLe Lhe edges wlLh suLures
O C) secondary repa|r (second |ntent|on)
O Jhen Lhere ls conslderable loss of Llssue and Lhe edges of wound cannoL be approlmaLed heallng proceeds Lhrough replacemenL of Lhe losL
Llssue by granu|at|on t|ssue scar (noL a regeneraLlon or resLlLuLlon ad lnLegrum) wound ls wlder amounL of scarrlng much greaLer
O Several sLages of wound closure (raLe of wound closure)
O LaLenL perlodslze of wound doesn'L change 1several days
O erlod of conLracLlon probably resulLs from shrlnkage of granulaLlon Llssue edges pull LogeLher
O pldermlsaLlonlaLer ln process Lhan conLracLlon
O Jound edges aparL 2023mmmlgraLlon of eplLhellal cells ceases requlres skln grafLlng cells on brldge don'L geL message Lo dlvlde lose
ablllLy Lo communlcaLe and dlvlde
17

Iactors |nf|uenc|ng rate of hea||ng
O Age (young/elderly don'L heal as well) slze of wound secondary lnfecLlon dleLary sLaLus (vlL vlL u proLeln lnLake) blood supply overall sLaLus
frall or healLhy?
O Pow may we lnfluence heallng?
O roLecL wound prompL lrrlgaLlon lmmoblllze ln[ured area (resL + lmmoblllzaLlon meLabollsm) avold manlpulaLlon dralnage of eudaLe and pus
admlnlsLraLlon of anLlbloLlcs lf lnfecLed nolous maLerlals removed (eclslon of devlLallzed LlssuesdebrldemenL) conLrol of bleedlng and removal
of ecesslvely cloLLed blood [udlclous use of suLure maLerlal preserve blood supply (no LlghL dresslng) elevaLe affecLed parLs Lo help draln apply
approprlaLe Lhermal modlflcaLlon (be cerLaln when cold and heaL should be applled) malnLaln opLlmal nuLrlLlonal sLaLus for a glven age
O nC SA8S 8raln (damaged areas [usL removed)
O 1lssue musL be vlable for heallng Lo occur no clrculaLlonno heallng
Maln phases of cuLaneous wound heallng lnflammaLlon formaLlon of granulaLlon and M remodelllng
uLaneous wounds can heal by prlmary unlon (flrsL lnLenLlon) or secondary unlon (secondary lnLenLlon)more eLenslve scarrlng and wound
conLracLlon
1oo much heallng ls bad e arLhrlLls
lnlLlal cross llnklng of flrbln removal of debrls chemoLalsfor flbroblasLs
8esoluLlon removal of cloL new Lemporary M (Lype lll collagendellcaLe/lmmaLure flrsL Lype of collagen produced) flnal M (Lype l
collagenadulL collagen cross llnked sLrong)
1enslle SLrengLh
8y Lhe 3rd day when Llssue debrls ls cleared
8y 1 week when Lhe gap ls brldged by granulaLlon Llssue
8y 2 monLhs afLer scar remodelllng has begun
rom 6 monLhs Lo 1 year afLer collagen crossllnklng
scars are always weaker Lhan lnLacL Llssue
neoplasla
O **rlm of normal Llssue ls removed around Lumour LooresecLlon margln
O 2 ouLcomes of cell ln[ury cell dles or allve goes on Lo adapL vla
ellular AdapLaLlon Lo SLress
1 ALrophy decreased ln slze and funcLlon of cell
O auses decreased workload decreased blood supply loss of lnnervaLlons lnLerrupLlon of Lrophlc slgnal aglng
O lf aLrophy perslsLs Lhe cells may dle
O ALrophy of Lhyrold followlng plLulLary resecLlon aLrophy of braln ln aglng (Alzhelmer's)
2 PyperLrophy lncrease ln Lhe slze of a cell accompanled by an augmenLed funcLlonal capaclLy
O auses lncreased funcLlon demand (myocardlal hyperLrophy ln hyperLenslonmuscles cannoL prollferaLe buL can lncrease ln slze
muscle hyperLrophy ln aLhleLes) physlologlcal (hormonal) hyperLrophy (se organs aL puberLy)
3 Pyperplasla lncrease ln Lhe number of cells ln an organ or Llssue
O auses lncreased funcLlonal demand (lncreased 88s ln hlgh alLlLudedecreased C2 levels so adapL by lncreaslng 88 producLlon)
hormonal sLlmulaLlon (endomeLrlum ln early phase of mensLrual cycle) perslsLenL cell ln[ury (skln ln calluses)all above are
P?SlCLCCl
O All are reverslble vla removlng sLlmulus
4 MeLaplasla converslon of one dlfferenLlaLed cell Lype Lo anoLher
O converslon of bronchlal clllaLed columnar eplLhellum Lo squamous eplLhellum ln smokers
O AlLhough lL's a proLecLlve mechanlsm Lhere may be loss of funcLlon
O ulfferenLlaLednormal
O noL cancer
O normal cell ul8n1 normal cell
3 uysplasla alLeraLlon ln slze shape and organlzaLlon of Lhe cellular componenLs of a Llssue
O eaLures
O varlaLlon ln shape and slze of cells (cellular pleomorphlsm)
O varlaLlon ln nuclear shape and slze (nuclear pleomorphlsm)
O nlargemenL lrregularlLy and hyperchromaLlsm of Lhe nuclel
O ulsordered arrangemenL of Lhe cell
O Slgnlflcance dysp|as|a |s a prema||gnant (|e No |nvas|on |s present) |es|on
O erslsLenL ln[ury may lead Lo dysplasla e uysplasla ln bronchlal eplLhellum dysplasla ln cervlcal eplLhellum
O dysplasLlc Llssue" blg and small nuclear slzes and cell slzes dlsorganlzed dlfferenL cells and dlfferenL slzes
O JhaL you look for ln a A smear
O SLandard ln eplLhellal mallgnancles
O aLch Lhem aL dysplasLlc sLaLe can geL 100 cure raLe
pldemlology
O 84800 anadlan women and 3000 anadlan men wlll be dlagnosed wlLh cancer
O 33100 women and 300 men wlll dle of cancer
O 3487 anadlans wlll be dlagnosed wlLh cancer every day 203 anadlans wlll dle of cancer every day
18

O anada 40 of women and 43 of men wlll develop some form of cancer and x wlll dle of lL
O neL Lo hearL dlsease mosL common cause of deaLh
O Leadlng cause of premaLure deaLh ln anada 1 mllllon poLenLlal years of llfe losL ln anada
Clossary
O neoplasla new growLh Lumour
O Cncology (oncosLumour) sLudy of Lumours
O ancermallgnanL neoplasm
O MallgnanL Lumour Lumour LhaL lnvades and spreads Lo dlsLanL slLes
O 8enlgn Lumour Lumour LhaL does noL lnvade or spread
O Neop|asm an abnormal mass of Llssue Lhe growLh of whlch eceeds and ln uncoordlnaLed wlLh LhaL of normal Llssue and perslsLs ln Lhe
same ecesslve manner afLer Lhe cessaLlon of Lhe sLlmulus whlch evoked Lhe change remove sLlmulus wlll noL change Lumour LhaL was
already sLarLed Lo grow
nomenclaLure
O neoplasms composed of prollferaLlng neoplasLlc cells and supporLlng sLroma classlfled accordlng Lo Lhe 1? of Lumour cells (lndlcaLlng
Llssue of orlgln) and nA1u8 of Lhe Lumour cell wheLher benlgn or mallgnanL
1 8enlgn 1umours have suffl oma" followlng Llssue Lype ma[orlLy are named by Llssue Lype some are named by archlLecLural paLLerns
O Adenoma benlgn Lumour LhaL forms gland or orlglnaLlng from glands andenogland
O apllloma benlgn Lumours wlLh flngerllke pro[ecLlons
O olyp elevaLed mucosal leslons (descrlpLlve Lerm) does noL mean Lumour unless quallfled
O Llpomabenlgn Lumour made of faL cells
O lbroma benlgn Lumour made of flbroblasL cells
O ysLadenoma an adenoma wlLh cysLlc areas
O **except|ons me|anoma]|ymphoma both are actua||y ma||gnant
2 MallgnanL 1umours slmllar sysLem as benlgn lf composed of MSnP?MAL(bone muscle Llssue) cells sarcoma (sarfleshy) lf composed
of l1PLlAL cells carclnoma
O AdenocarclnomamallgnanL eplLhellal Lumour wlLh cells formlng glandular(mucln secreLlng) growLh paLLern
O Squamous cell carclnoma mallgnanL eplLhellal Lumour composed of squamous cells
O lbrosarcoma mallgnanL mesenchymal Lumour composed of flbrous Llssue
O 1umours may show dlvergenL dlfferenLlaLlon MlOu(more Lhan one Lype of Lumour cell) Lumours Lhey can be elLher benlgn or
mallgnanL
O 1eratoma mled Lumour conslsLlng of 2 or more germ layers arlslng from mesenchymal cells ovary and LesLls could elLher be benlgn or
mallgnanL
3 CLher Lerms
O horlsLoma ecLoplc resL nC1 a Lumour normal Llssue ln abnormal places e pancreaLlc Llssue ln small bowel
O PamarLoma dlsorganlzed normal Llssue ln normal locaLlon
O ysL fluld fllled space
haracLerlsLlcs of 8enlgn and MallgnanL neoplasms
1 ulfferenLlaLlon and Anaplasla (maLurlLy)
O ulfferenLlaLlon eLenL Lo whlch Lumour cells resembles normal counLerparL (morphologlcally and funcLlonally)
O Jell(slmllar Lo normal cell) moderaLely or poorly dlfferenLlaLed
O All benlgn Lumours are JLL dlfferenLlaLed PCJv8 all well dlfferenLlaLed Lumours are nC1 all benlgn
O Lack of dlfferenLlaLlon AnALASlA characLerlsLlc of mallgnancy used wlLh respecL Lo an lnvaslve neoplasm
O Lack of varlous degrees of dlfferenLlaLlon ls a characLerlsLlc of mallgnancy
O Ieatures of Anap|ast|c (Und|fferent|ated) Ce||s
O varlable cell slze and shape (cellular pleomorphlsm) varlable nuclear slze and shape (nuclear pleomorphlsm) hyperchromaLlc nuclel
(lncreased nuclearcyLoplasmlc raLlo) lncreased mlLosls and aLyplcal mlLosls loss of polarlLy Lumour glanL cell
O **looks llke dysplasLlc buL CnL? use AnALAS1l Lo descrlbe lnvaslve neoplasm
O Iunct|ona| D|fferent|at|on
O orrelaLe roughly wlLh sLrucLural dlfferenLlaLlon poorly dlfferenLlaLed Lumours are less funcLlonally acLlve (e keraLln producLlon by
squamous cell carclnoma hormone producLlon by endocrlne carclnoma)
O 8lochemlcal convergence ln poor dlfferenLlaLed Lumour (Lhey resemble each oLher raLher Lhan cell of orlgln)
O new funcLlons
O Jell dlfferenLlaLed lncrease keraLln poorly dlfferenLlaLed decreased hormone producLlon
O hormone secreLlon (bronchogenlc carclnoma)
2 8aLe of CrowLh
O 8enlgn Lumours are slow growlng mallgnanL Lumours are AS1 growlng except|on growth of |e|omyoma dur|ng pregnancyhormone
dependent ones can |ncrease growth rate)
O 8aLe of growLh correlaLes wlLh blood supply
O 8aLe of growLh lnv8SL? correlaLes wlLh dlfferenLlaLlon poorly dlfferenLlaLed Lumours grow AS18
O asL growlng Lumours may undergo cenLral necrosls due Lo rapld growLh
3 lnvaslon
1

O neL Lo meLasLasls lnvaslon ls a rellable feaLure of mallgnancy
O 8enlgn Lumours are clrcumscrlbed and uC nC1 lnvade (malnLaln geographlc boundary) Lhey grow by epanslon and show a rlm of
compressed sLromal and connecLlve Llssue (aka capsule) the absence of a capsu|e |s NC1 a|ways equ|va|ent to ma||gnancy
O MosL carclnomas begln as locallzed growLh orlglnaLlng from a SlnCL cell and are conflned Lo Lhe eplLhellum of orlgln as long as Lhe
basemenL membrane ls lnLacL Lhey are Lermed carc|noma |n s|tu (severe dysplasla) carclnoma ln lLs place (hasn'L sLarLed lnvadlng yeL)
lnLraeplLhellal neoplasla carclnoma ln slLu severe dysplasla hasn'L lnvaded yeL
O MallgnanL Lumours lnvade and desLroy Lhe Llssue may appear clrcumscrlbed on gross eamlnaLlon 8u1 mlcroscoplcally lnC8 Ll
lnvaslon are seen conLlnuous spread of cells
4 MeLasLasls
O MeLasLasls ls a Lumour lmplanL d|scont|nuous from Lhe prlmary Lumour (hlsLologlcally Lhe same cancer) meLasLasls ls unequlvocal slgn of
mallgnancy
O Jlll look llke cancer where lL orlglnaLed call lL cancer from whlch lL orlglnaLed
O lnvaslon conLlnuous spread
O MeLasLasls dlsconLlnuous spread benlgn Lumours do noL meLasLaslze
O lnvaslon before meLasLasls
O aLhways of meLasLasls
O A) seed|ng v|a body cav|t|es
O erlLoneal cavlLymosL common
O erlcardlal/pleural/subarachnold cavlLles
O g Cvarlan carclnoma (perlLoneal cavlLy)
O 8) |ymphat|c spread
O MosL common lnlLlal dlssemlnaLlon
O ollows naLural dralnage
O nlarged lymph nodes ln cancer paLlenL noL always meLasLasls (depends on hlsLologlcal conflrmaLlon)
O C) hematogenous spread
O 8lood/bone spread
O avoured by sarcoma buL carclnoma also use lL
O Llver and lung are frequenL slLes
O lnLravenous growLh ln renal cell carclnoma
O ollow rouLes of venous dralnage
MallgnanL vs 8enlgn 1umours
Character|st|cs 8en|gn Ma||gnant
ulfferenLlaLlon/anaplasla JelldlfferenLlaLed sLrucLure may
be Lyplcal of Llssue of orlgln
Some lack of dlfferenLlaLlon wlLh
anaplasla sLrucLure ls ofLen aLyplcal
8aLe of growLh usually progresslve and slow may
come Lo sLandsLlll or regress
mlLoLlc flgures are rare and normal
rraLlc and may be slow Lo rapld
mlLoLlc flgures may be numerous
and abnormal
Local lnvaslon usually coheslve and epanslle well
demarcaLed masses LhaL do noL
lnvade or lnfllLraLe Lhe surroundlng
normal Llssues
Locally lnvaslve lnfllLraLlng Lhe
surroundlng and normal Llssues
someLlmes may be seemlngly
coheslve and epanslle
meLasLasls absenL requenLly presenL Lhe larger and
more undlfferenLlaLed Lhe prlmary
Lhe more llkely Lo meLasLases

**see nomenclaLure Lable p46
8lology of 1umour CrowLh
O naLural hlsLory of mallgnanL Lumour conslsLs of 4 phases
O 1 1ransformaLlon a normal cell changed Lo a mallgnanL cell (carclnogenesls)
O 2 CrowLh of Lransformed cell (anglogenesls Lumour progresslon)
O 3 Local lnvaslon
O 4 ulsLanL meLasLases
1 1he Lransformed cell
O MosL human Lumours are derlved from a SlnCL Lransformed cell (monoclonal ln orlgln)
O 1umour cells may noL be sub[ecL Lo normal growLh and dlfferenLlaLlon conLrol Lhey show
O Self sufflclency ln growLh slgnal
O lnsenslLlvlLy Lo growLhlnhlblLory slgnals auLonomous (don'L llsLen Lo anyone)
O 8eslsLanL Lo apopLosls
O uefecLlve unA repalr
O unresLrlcLed prollferaLlon
O Anglogenesls lnvaslon and meLasLasls
20

2 1umour growLh
O 1lme requlred for a Lumour Lo double ln volume or mass depends on
O A) growLh fracLlon # of cycllng cells/ # of LoLal cells
O 8) cell loss facLor
O 1umours ecess cell producLlon over loss produclng a rapld growLh cell producLlon cell loss a loL more prollferaLlng cells
O ells are losL Lo apopLosls lschemla and hosL defence mechanlsms
O 1umour cells go Lhrough cell cycle phases slmllar Lo normal cells doubllng Llme of Lumour cells are slmllar Lo or someLlmes more Lhan
normal counLerparL
O arller ma[orlLy of cells are ln Lhe prollferaLlve pool
O 1umours wlLh hlgh growLh fracLlons are suscepLlble Lo chemoLherapy
O Mlnlmum slze for deLecLable Lumour 1cm3 (1gm) 10810 cells Lhls LranslaLes Lo 30 doubllng from a slngle cell (noL lncludlng cell
loss) 10 populaLlon doubllngs from Lhls sLage well lead Lo a Lumour slze of 1kg (leLhal)
3 1umour Anglogenesls
O 8lood supply a ma[or facLor modlfylng growLh (need food Lo grow)
O Anglogenlc facLors (creaLlon of new blood vessels)
O roduced by Lumour cells (noL normal cells)
O roduced by lnflammaLory cells lnfllLraLlng Lumour
O hemoLacLlc and mlLogenlc for endoLhellal cells (cause endoLhellal cells Lo prollferaLe allowlng blood vessels Lo grow)
O lnduce producLlon of proLeolyLlc enzymes
O lbroblasL growLh facLors (Cs) vascular endoLhellal growLh facLor (vC) plaLeleL derlved growLh facLor (uC) hypola lnduclble
facLor 1 (P11)
O **chemoLherapy LargeLs desLrucLlon of Lhese blood vessels
4 1umour progresslon and PeLerogenelLy
O Cver a perlod of Llme Lumour may acqulre greaLer mallgnanL poLenLlal due Lo varlous subpopulaLlons of cells LhaL may sequenLlally
appear subpopulaLlon may vary ln anLlgenlclLy lnvaslveness meLasLaLlc poLenLlal growLh facLor requlremenL eLc
O SubpopulaLlon beaL Lhe odds" and survlve Lhe raLe aL whlch Lhese subpopulaLlons are generaLed ls varlable
O All subpopulaLlons have a dlsLlncL eperLlse form an army
O All begln from one cell and acqulre muLaLlons
O **mallgnanL ls a dlfferenL paLhway from benlgn sLarL mallgnanL and end mallgnanL one usually doesn'L sLarL from one anoLher
Mechanlsms of 1umour lnvaslon and MeLasLasls
O Several sLeps ln Lhe process of a mallgnanL Lumour peneLraLlng a conflnlng basemenL membrane and Lhen lnvadlng surroundlng
eLracellular envlronmenL
O 1 Lose cadherln and become moblle cell (deLachmenL of Lumour cells)
O 1 roLeolyLlc enzymes (collegenase) are released from Lhe Lumour cells and Lhe eLracellular maLrl ls degraded
O 2 1he Lumour acqulres Lhe ablllLy Lo blnd Lo alLered componenLs of Lhe maLrl Lhese lnLeracLlons are medlaLed by Lhe epresslon of a
number of adheslon molecules
O 3 AfLer movlng Lhrough Lhe envlronmenL Lhe lnvadlng cancer peneLraLes blood vessels and lymphaLlcs by Lhe same mechanlsms
O 4 1he Lumour cells enLer Lhe clrculaLlon eLravasaLe ln Lhe meLasLaLlc slLe and grow
3 Mechanlsm of Local and ulsLanL Spread
O As Lumours grow cerLaln subclones acqulre more meLasLaLlc poLenLlal Lhan oLhers 2 phases of meLasLasls are lmporLanL
O A) |nvas|on of extrace||u|ar matr|x
O ancer cells are less adherenL Lo each oLher due Lo lack of AMs Lhey degrade basemenL membranes be secreLlon of proLeolyLlc
enzymes LhaL dlssolve maLrl proLelns (collagenase caLhespln 8 plasmlnogen acLlvaLors) benlgn Lumours secreLe llLLle or no such
enzymes
O 1hey aLLach Lo Lhe basemenL membrane Lhrough lamlnln recepLors and lnLegrlns
O LocomoLlon of Lumour cells Lrlggers cyLoklnes such as auLocrlne moLlllLy facLors secreLed by Lumour cells and cleavage producLs of maLrl
componenL
O 8) vascu|ar d|ssem|nat|on and hom|ng (metastat|c s|te) of tumour ce||s
O Slngle or many Lumour cells form emboll by aggregaLlng wlLh plaLeleLs and J8 Lhey form adheslon wlLh endoLhellum and flnally elL
Lhrough basemenL membrane
O SlLe of meLasLasls may be predlcLed by vascular or lymphaLlc dralnage
O 1he homlng may be relaLed Lo Lhe followlng facLors
O resence or absence of endoLhellal adheslve molecules ln some slLes
O hemoaLLracLant
O unfavourable envlronmenL (e skeleLal muscles)
O **ln Lhe new slLe have Lo grow and galn new blood supply
O Pomlng new meLasLaLlc slLe
C||n|ca| Ieatures of 1umours
1 ffecL of Lumour on hosL
O A) |oca| effects
O effecLs may be varled dependlng on locaLlon and lnfrlngemenL seen ln 8C1P benlgn and mallgnanL neoplasm
21

O benlgn submucosal lelomyombleedlng
O neoplasms (benlgn or mallgnanL ln guL) obsLrucLlon
O plLulLary adenomaepanslle growLhs and desLrucLlon of remalnlng gland
O gasLrolnLesLlnal Lumours/urogenlLal Lumours bleedlng
O ovarlan Lumours Lorslon
O **Lumour may undergo lnfracLlon rupLure ulceraLlon and secondary lnfecLlon
O 8) hormona| effects
O 8 cell adenoma ln pancreas lnsulln hypoglycaemla may be leLhal
O Adrenal corLe adenoma sLerold secondary effecLs
O arclnold Lumour hormones carclnold syndrome
O C) Cancer Cachex|a
O rogresslve loss of faL and lean body mass wlLh weakness anorela and anemla nC1 due Lo nuLrlLlonal demand by Lumour several
facLors may be responslble
O 8educed food lnLake abnormallLles of LasLe and cenLral conLrol
O 8educed synLhesls and sLorage of faL lncreased moblllzaLlon of faLLy aclds from adlpocyLes
O robably candldaLe Lumour necrosls facLor (1n) whlch eperlmenLally mlmlcs cancer cachela
O D) araneop|ast|c Syndome
O SympLom comple ln cancer bearlng paLlenLs LhaL cannoL readlly be eplalned elLher by local or dlsLanL spread of Lumour or by Lhe
elaboraLlon of Lhe hormones lndlgenous(belonglng ln LhaL place) Lo Lhe Llssue of orlgln
O lmporLance
O May be earllesL manlfesLaLlon of an occulL neoplasm
O May cause slgnlflcanL even leLhal cllnlcal problem
O May mlmlc meLasLaLlc dlsease
O Lx 8ronchogen|c carc|noma may cause
O ushlng's Syndrome Syndrome of lnapproprlaLe AuP secrecLlon hypercalcemla myesLhesla acanLhosls nlgrlcans hyperLrophlc
osLeoarLhropaLhy venous Lhrombosls
O **see charL on p48
2 Cradlng and SLaglng of ancerlnfo needed Lo LreaL
O A) Grad|ng an esLlmaLe of aggresslveness of Lhe neoplasm and based on Lhe level of ul8n1lA1lCn varlable crlLerla are used
O ommonly based on dlfferenLlaLlon mlLosls and necrosls
O ommonly descrlbed as well moderaLely or poorly dlfferenLlaLed Lumours
O Speclflc Lo a speclflc cancer Lype
O 8) Stag|ng of greaLer cllnlcal lmporLance Lhan gradlng based on Lumour slze lymph node spread and meLasLasls Lo oLher organs
O llolcol stoqloq based on evldence acqulred prlor Lo declslon as Lo deflnlLlve LreaLmenL
O 9otboloqlcol stoqloq lncludes lnformaLlon obLalned aL surgery and from eamlnaLlon of Llssues by paLhologlsLs
O SLaglng ls based on slze of prlmary leslon eLenL of spread Lo reglonal lymph nodes and presence or absence of bloodborne meLasLases
O 2 ma[or sysLems
O 1he 1NM (1tumour Nnodes Mmetastases) System developed by Lhe unlon lnLernaLlonale onLre ancer (ul)
O Amer|can Io|nt Comm|ttee (AIC) on Cancer Stag|ng dlvldes Lumours lnLo sLages C Lo lv uslng facLors slmllar Lo Lhe 1nM sysLem
O **unlversally accepLed sLaglng only applles Lo mallgnanL
O **sLage and Lhen grade all cancers aL same sLage go Lo gradlng Lo see who wlll do beLLer
3 LaboraLory ulagnosls of ancer
O llnlcal lnfo ls of greaL lmporLance wlLhouL cllnlcal lnfo an lncorrecL dlagnosls ls easlly reached
O Surglcal paLhology |s NC1 slmllar Lo blood glucose measuremenL
O A) t|ssues used for dlagnosls may be ln Lhe followlng sLaLes
O resh formalln fled oLher flaLlves (gluLeraldehyde) flne needle asplraLlons cyLology smear
O 8) samp||ng methods lnclude
O 8lopsy eclslon flne needle asplraLlon blopsy smear body fluld
O C) t|ssue process|ng
O ormalln flaLlve dehydraLlon ln graded alcohol ylene paraffln embeddlng secLlons cuL and sLalned wlLh hemaLoylln and eosln
O D) f|ne need|e asp|rat|on b|opsy (NIA8)
O useful for palpable leslons
O Cfflce procedureLhyrold breasL sallvary glands
O ueeper Llssue (llver)lmaglng gulded
O Smear cell blocks
O L) cyto|og|c smear
O ervlcal cancer deLecLlon
O an be adapLed for oLher leslons
O I) cyto|ogy of body f|u|ds
O leural and perlLoneal fluld S spuLum urlne
22

O G) add|t|ona| techn|ques
O lmmunocyLochemlsLry elecLron mlcroscopy flow cyLomeLrlc analysls (marker unA ploldy) molecular dlagnosls cyLogeneLlcs
O n) b|ochem|ca| tumour markers
O SA (prosLaLe speclflc anLlgens)prosLaLlc adenocarclnoma
O **Lhey are noL dlagnosLlc as Lhey may be elevaLed ln lnflammaLory condlLlons used ln screenlng
Carc|nogenes|s
1 redlsposlng acLors
O A) geograph|c factors
O Age ad[usLed deaLh raLe for breasL cancer uS27 ngland36 !apan7
O SLomach cancer 7 hlgher ln !apan Lhan uS
O PepaLocellular carclnoma lnfrequenL ln uS some Afrlcan populaLlons #1 leLhal cancer
O 8) env|ronmenta| |nf|uence
O Smoklng sunllghL
O C) Age
O ln general lncreases wlLh age peak 3373 yrs
O **except|ons
O Sarcomas younger age group (osLeosarcoma)
O hlldhood cancers (occurs ecluslvely ln chlldren) neuroblasLomas wllms reLlnoblasLoma
O D) hered|tary (def|n|te hered|tary pred|spos|t|on)
O l) lnherlLed cancer syndromes (auLosomal domlnanL) Mn (mulLlple endocrlne neoplasla)
O ll) famlllal cancers (shows clusLerlng buL heredlLary predlsposlLlon ln lndlvldual cases lsn'L clear) breasL/colon/ovary
O lll) heredlLary preneoplasLlc condlLlons unA repalr defecL (auLosomal recesslve)e eroderma plgmenLosa
O L) acqu|red preneop|ast|c cond|t|ons
O 8arreLL's esophagus (lnLesLlnal meLaplasla) adenocarclnoma
2 Carc|nogen|c Agents
O ancer ls a geneLlc dlsease geneLlc damage can be caused by chemlcals physlcal agenLs or by blologlcal agenLs
O Carc|nogen|c agents causlng geneLlc damage may be chemlcals physlcal agenLs such as radlaLlon oncogenlc vlrus bacLerla
O A) chem|ca| carc|nogens
O ulverse naLural and synLheLlc producLs may be dlrecL acLlng or lndlrecL acLlng (followlng converslon ln Lhe body) from precarclnogens Lo
carclnogens ln Lhe body
O Plghly reacLlve molecules whlch reacLs wlLh 8nA or unA or proLelns
O Several may acL LogeLher or along wlLh oLher vlrus or radlaLlon
O 8) rad|at|on carc|nogenes|s
O 8adlanL energy wheLher ln Lhe form of uv rays of sunllghL or as lonlzlng elecLromagneLlc and parLlculaLe radlaLlon can Lransform vlrLually
all cell Lypes ln vlLro and lnduce neoplasm ln vlvo ln boLh humans and anlmals eamples
O uv rays squamous cell carclnoma
O lonlzlng radlaLlon leukemla
O 8adlaLlon dlrecLly lonlzes and damages crlLlcal cellular macromolecules
O 8adlaLlon also produces free radlcals LhaL medlaLe Lhe damage
O C) v|ra| oncogenes|s
O A large number of vlruses have proved Lo be oncogenlc ln anlmals only a few have been llnked wlLh human cancer oncogenlc vlruses fall
lnLo 2 classes
O l) unA oncogenlc vlruses
O Pv (human papllloma vlrus)cervlcal cancer
O 8v (psLeln8arr vlrus)nasopharyngeal cancer 8urklLL's lymphoma
O P8v (hepaLlLls 8 vlrus)hepaLocellular cancer
O ll) 8nA oncogenlc vlruses
O Puman 1cell leukemla vlrus (P1Lv1)human 1 cell leukemla/lymphoma
O D) bacter|a| |nfect|on
O P ylorl lnfecLlon ls assoclaLed wlLh 8 cell lymphoma ln Lhe Mucosa AssoclaLlon LymphaLlc 1lssues (MAL1oma)
Mechanlsms of arclnogenesls
O nonleLhal geneLlc damage ls a key evenL ln carclnogenesls whlch may be caused by chemlcals radlaLlon or vlruses
O 1 Genet|c change |n tumours
O May be subLle (polnL muLaLlons) or large Lo be deLecLed as chromosomal changes
O A) karyotyp|c changes
O 8alanced LranslocaLlon MLL(22)
O deleLlonreLlnoblasLoma del 13q14
O gene ampllflcaLlon neuroblasLoma nM?
O 8) po|nt mutat|ons
O 8AS ln colon carclnoma
23

O **arclnogenesls effecLs several classes of genes such as
O Cncogenes Lumour suppressor genes apopLosls regulaLlng genes muLaLor (careLaker) genes
O **carclnogenesls ls a mulLl sLep process
2 Cncogenes and Cancer
O roLooncogenes normal genes LhaL play key roles ln conLrolllng cell prollferaLlon and dlfferenLlaLlon
O Cncogenes deregulaLed or alLered proLooncogenes LhaL lead Lo developmenL of cancer
O Act|vat|on of oncogenes can be secondary Lo change ln gene sLrucLure of due Lo a change ln regulaLlon of gene epresslon changes are
secondary Lo Lhe followlng mechanlsms
O a) polnL muLaLlons 8AS muLaLlon ls Lhe mosL common muLaLlon ln human cancer
O b) LranslocaLlon L(22) ln chronlc myelold leukemla
O c) gene ampllflcaLlon nM? ln neuroblasLoma
O rote|n products of oncogenes oncogenes encode for proLeln producLs called oncoproLelns Lhey are devold of regulaLory elemenLs
oncogenes may lead Lo developmenL of Lumour by acLlng aL dlfferenL levels of slgnal LransducLlon
3 1umour Suppressor Genes
O 1hese genes acL as an lnhlblLor of cell prollferaLlon when muLaLed Lhe lnhlblLlon ls losL
O 33 lung colon breasL ovary and oLher cancers
O n1 heredlLary neuroflbromaLosls
O A adenomaLous polyposl coll
O u deleLed ln colon cancer
O J11 Jllm's Lumour 1
O 88 reLlnoblasLoma
4 Apoptos|s kegu|at|ng Genes
O Cenes LhaL prevenL or lnduce apopLosls may be lmporLanL ln carclnogenesls
O 8L2 ln lymphoma
S Mutator (caretaker) genes
O unA repalr genes are nC1 oncogenlc by Lhemselves
O Jhen muLaLed however Lhey allow muLaLlon ln oLher genes ln normal cell dlvlslon
O hMSP2 LMLP ln heredlLary nonpolyposls colon
6 1e|omeres
O resenL aL Lhe end of Lhe chromosome are progresslvely shorLened wlLh age
O ancer cells and normal germ cells epress Lhe enzyme Lelomerase whlch malnLaln Lhelr ablllLy Lo repllcaLe
7 Lp|genet|c
O unA meLhylaLlon hlsLone aceLylaLlon and deaceLylaLlon play lmporLanL roles ln carclnogenesls
8 Mo|ecu|ar 8as|s of Mu|t| Step Carc|nogenes|s
O MulLlple oncogenes as well as one or mulLlple Lumour suprressor genes works LogeLher Lo produce cancer