Presentedby
CONTENTS:
Definition
Typesofinflammation
Eventsininflammation
Mediatorsininflammation
Inflammatorycells
Regulationofinflammation
Fateofinflammation
Systemiceffectsofinflammation
Inflammation:
Definedaslocalresponseoflivingmammalian
tissuestoinjuryduetoanyagent.Itisabody
defensereactiontoeliminateorlimitthespread
ofinjuriousagentaswellastoremovethe
consequentnecrosedcellsandtissues.
Inflammationisacomplexreactiontoinjurious
agentssuchasmicrobes,&damagedusually
necroticcells,thatconsistsofvascularresponse,
migration&activationofleucocytes&systemic
reaction
CARDINALSIGNS:
Rubor
Calor
Tumor
Dolor
Functio
laesa
RomanwriterCelsusin1stcenturyAD
INFLAMMATIONVSINFECTION
Inflammationisaprotectiveresponse
Infectionisinvasionofmicroorganismsintothe
host
Inflammationishelpfultobodywhileinfectionis
harmful
Inflammationisfollowedbyhealingwhile
infectionisfollowedbydamagetothehosttissue
TYPESOFINFLAMMATION
Acuteinflammation
Rapidonset
Shortduration&lastsforminutesorseveral
hours
Characteristicfinding
Exudationoffluid&plasmaproteins
Emigrationofleucocytespredominantly
Neutrophils
Intravascularactivationofplatelets
Chronicinflammation
Longerduration
Occurseitherafterthecausativeagentofacute
inflammationpersistsforlongtimeorthestimulus
issuchthatitinduceschronicinflammationfrom
thebeginning
Characteristicfinding
Infiltrationoflymphocytes¯ophages
Proliferationofbloodvessels
Fibrosis
Tissuenecrosis
GRANULOMATOUSINFLAMMATION:
Granulomatosinflammationisadistinctive
patternofchronicinflammatoryreactioninwhich
thepredominantcelltypeisanactivated
macrophagewithamodifiedepitheliallike
(epitheloid)appearance.
ACUTEINFLAMMATION:
DEFINITION
Acuteinflammationisrapidresponseto
injuriousagentthatservestodeliver
mediatorsofhostdefensetothesiteof
injury
3componentsofAcuteinflammation
Alterationsinvascularcaliberleadingto
increasedbloodflow
Structuralchangesinmicrovasculaturethat
permitsplasmaproteins&leucocytesfromthe
microcirculation
Emigrationofleucocytesfromthe
microcirculation,theiraccumulationinfocusof
injury&theiractivationtoeliminatethe
offendingorganism
STIMULIFORACUTE
INFLAMMATION:
Infectionsbacterial,viral,microbialtoxins,&
parasites
Traumablunt&penetrating
Physicalagents&chemicalagentse.g.thermal
injurylikeburnsorfrostbite,irradiation&
someenvironmentalchemicals
Tissuenecrosis
Foreignbodies
Immunereactions(hypersensitivity)
EVENTSOFACUTEINFLAMMATION:
Thechiefeventsofacuteinflammationcanbe
groupedinto:
Vascularevents
Cellularevents
VASCULARCHANGES:
Changesinvascularflow&caliber
Vasoconstrictionforfewseconds(transient)
vasodilatationofarteriolesincreasedvascular
flowheat&redness
Increasedpermeabilityofmicrovasculature
outpouringofproteinrichfluidintotissues
Lossoffluidconc.OfRBCinbloodvessels
increasedviscosityofbloodSTASIS
Formationofendothelialgapsinvenules:
Ismediatedbyhistamine,leucotrienesetc
Fast&shortlived(immediatetransient
response).
Bindingofthemediatorstoreceptorsonendothelium
Activatesintracellularsignalingpathway
Phosphorylationofcontractile&cytoskeletalproteins
(myosin)
Contractionofendothelialcells&separationof
intercellularjunctions
Gapsinvenularendotheliumwhicharelargely
intercellular
Directinjury:
Leadstocellnecrosis
Arterioles,capillaries&venules
DuetoToxins,burns&chemicals
Fast&maybelonglived(hourstodays)
Leucocytedependentinjury:
Mostlyvenules,pulmonarycapillaries&
glomerularcapillaries
Lateresponse&longlived(hours)
Earlystageleucocyteadheretoendothelium
activatedreleasetoxicoxygenspecies&
proteolyticenzymesendothelialinjury&
detachmentincreasedpermeability
Increasedtranscytosis:
Itoccursacrossthechannelsconsistingof
clustersofinterconnected&uncoatedvesicles
&vacuolescalledvesicovacuolarorganelles
whicharelocatednearintercellularjunctions
Increasedvascularleakagebyincreasingthe
number&sizeofthesechannels
Leakagefromnewbloodvessels:
Newbloodvesselformedareleakyuntil
endothelialcellsmature
Factorscausingangiogenesisalsoincrease
thevascularpermeability
CELLULAREVENTS:
Thisphaseconsistsoftwoevents:
Exudationofleukocytes
Phagocytosis
Sequenceofeventsintheextravasationsof
leucocytes:
InthelumenMargination,Rolling&Adhesion
toendothelium
Diapedesistransmigrationacrossthe
endothelium(passive,RBC)
Migrationintheinterstitialtissuetowards
chemotacticagent
Leucocyteadhesion&transmigrationis
regulatedbybindingofcomplementaryadhesion
moleculesontheleukocyte&endothelial
surfaces,&chemicalmediators
chemoattractants&certaincytokines
affecttheseprocessesbymodulatingthesurface
expressionoravidityofsuchadhesionmolecules
ADHESIONRECEPTORMOLECULE:
Adhesionreceptormoleculesare
Selectin
Immunoglobulinforma)ICAM1
b)VCAM1
Integrins
MucinlikeglycoproteinHeparinsulphate
ADHESIONRECEPTORMOLECULE:
SELECTINS
Bindingiscalciumdependent
3typesa)Lselectin(CD62L)
b)Eselectin(CD62E)
c)Pselectin(CD62P)
SELECTINS
LSelectin(CD62L)
Functions
Homingreceptorforlymphocyte
Bindingneutrophilstoendothelialcells
Locatedattipsofmicrovilliprojectionof
leucocytes
Bindsto3ligandsa)Glycam1
b)Madcam1
c)CD34
ESelectins(CD62E)
Recognizesacomplexsialalatedcarbohydrate
grouprelatedtoLewisX&LewisAwhichare
foundoncellsurfaceproteinsofgranulocytes,
monocytes,&Tcells
Functionhomingofeffector&memoryTcells
toparticularsiteofinflammatione.g.skin
PSelectin(CD62P)
Identifiedinsecretorygranulesofplatelets
Presentinsecretorygranulesofendothelialcells
Weibelpaladebodies
Functionisactivationofendothelialcells&
platelets
ADHESIONRECEPTORMOLECULE
INTEGRINS:
Theseproteinspromotecellcell&cell
matrixinteractions
Theyintegratesignalsfromextracellular
ligandwithcytoskeletondependent
motility,shapechange&phagocytic
responses
Theyarecomposedoftwononcovalentlylinked
polypeptidechainsi.e.Alpha&Beta
Extracellulardomainsoftwochainsbindto
variousligandssuchasextracellularmatrix
glycoproteins,activatedcomplementcomponents
&proteinsonthesurfaceofothercells
OnthebasisofBetasubunits,subfamiliesofthe
integrinshavebeenclassified.Theyare
Beta1integrinsalsocalledCD49ahCD29
Beta2integrinsalsocalledCD11acCD18or
LFA1
CD11bCD18
Eventsininductionofadhesionmoleculeson
endothelialcellsbyanumberofmechanisms:
MediatorssuchasHistamine,thrombin&PAF
stimulateredistributionofPselectinfromits
normalintracellularstore(granule)tocell
surface
Residenttissuemacrophages&mastcellssecrete
cytokines&chemokines
TNF&IL1actonEndothelialcellsofpost
capillaryvenulesadjacenttoinfection&induces
theexpressionofseveraladhesionmolecules
CHEMOTAXIS
Definition:
Locomotionorientedalongthechemicalgradient
Chemoattractants:
Theycanbe
ExogenousBacterialproducts
Endogenousa)componentsofcomplement systeme.g.
C5a
b)ProductsofLipoxygenase pathwaymainly
Leukotrienes
c)Cytokines
Chemotacticagentsbindsto7transmembraneG
coupledreceptors
signalsinitiatedbythese
receptors
RecruitmentofActivationofseveral
Gproteins effectormolecules
likePhospholipaseC
(PLCgamma)
Phosphoinositol3kinase
(PI3K)&proteintyrosine
kinase
PLCGamma&PI3K
Actonmembraneinositolphospholipids
Generatinglipidsecondmessengers
increasingcytosoliccalcium
ActivationofGTPasesofRac/Rho/cdc42
familyaswellasnumerouskinases
Polymerisationofactinattheleadingedge
ofthecell
LEUCOCYTEACTIVATION:
Thefunctionalresponsesthatareinducedon
leucocyteactivation:
PhospholipaseA2activationbyintracellular
calcium&othersignalsconvertsphospholipids
intoArachidonicacidmetabolites
Degranulation&secretionoflysosomalenzymes&
activationofoxidativeburst
Secretionofcytokinesbymacrophagesleadsto
amplificationofinflammatoryresponse
Modulationofleucocyteadhesionmolecule
IntherestingstateGproteinformastableinactive
complexcontainingGuaninediphosphateboundtoG
alphasubunit
OccupancyoftheligandsleadstoexchangeofGTPfor
GDP
GTPboundformoftheGproteinactivatesnumerous
cellularenzymesincludingisoformofPhosphotidylinositol
specificphospholipaseCdegradesinositol
phospholipidsintracellularcalciumactivationof
proteinkinaseCreleaseofmicrobicidalsubstances
OPSONIZATION&OPSONINS:
Theprocessofcoatingparticle,suchasamicrobe,to
targetitforphagocytosisiscalledOpsonization&
substancesthatcoatarecalledOpsonins
Efficientopsoninsare
IgGantibodies
componentsofcomplement
MannosebindingLectin
Fibronectin
Fibronogen
Creactiveprotein
PHAGOCYTOSIS:
CellEating
EngulfmentOfSolidParticlesByTheCell
MainlyPerformedBy:
LeukocytesInTheFirstline
MacrophagesInTheLaterStages
Stagesofphagocytosis:
Recognitionandattachmentstage(opsonins)
Engulfmentstage
Degranulationstage
Degradationstage
ENGULFMENTSTAGE:
Formationofcytoplasmicpseudopods
Activationofactinfilaments
Releaseinfreecytoplasm
Vacuolarenvolopment
Formationofphagolysosome
DEGRANULATIONSTAGE:
Releaseofstoredgranulesintheleukocytes
FusionofAzurophilicgranules
Activationofarachidonicacidmetabolites
Superoxideformation
DEGRADATIONSTAGE:
Alsocalledkillingstage
Completedigestionofforeigncellsandtheir
scavenging
Types:
Oxygendependentkilling
Oxygenindependentkilling
Nitricoxidemechanism
MEDIATORSOFINFLAMMATION:
Alsoknownas
Permeabilityfactors
Endogenousmediators
Derivedfrom:
Cells
Plasma
Damagedtissueitself
2types:
Fromthecells
Fromtheplasma
Cellderived:
Vasoactiveamines
Eicosinoids
Lysosomalcomponents
PAF
cytokines
Plasmaderived:
Theyaretheproductsof:
Thekininsystem
Theclottingsystem
Thefibrinolyticsystem
Thecomplementsystem
REGULATIONOFINFLAMMATION:
Inflammationisadoubleedgedsword
Inseverestagesitmaydamagethehosttissue,
henceitshouldberegulated
Regulationiscarriedoutby:
Acutephaseproteins
Corticosteroids
Freecytokinereceptors
SuppressorTcells
Antiinflammatorymediators
FACTORSDETERMINING
VARIATIONOFINFLAMMATORY
RESPONSE:
Thesefactorsare:
1)involvingtheorganism
2)involvingthehost
3)typeofexudation
4)cellularproliferation
5)necrosis
FACTORSINVOLVINGTHE
ORGANISM:
Typeofinjuryandinfection
Virulence
Dose
Portalofentry
Productoftheorganism
FACTORSINVOLVINGTHEHOST:
Generalhealthofthehost
Immunestatusofthehost
Leucopenia
Typeoftissueinvolved
Localhostfactors
TYPEOFEXUDATION:
Serous
Purulent
Fibrinous
Heamorrhagic
catarrhal
CELLULARPROLOFERATION:
Thechiefvariablefactor
Differsin
Bacterialinfections
Viralinfections
ProgressiveGlomerulonephritis
Inchronicinflammation
NECROSIS:
Extentofnecrosisisvariable
Gasgangreneextensivenecrosiswithfoulsmell
Appendicitisnecrosisduetovascularobtruction
ChronicinflammationCaseousnecrosis
MORPHOLOGYOFACUTE
INFLAMMATION:
Morphologicvarietiesofacuteinflammation:
Pseudomembranousinflammation
Ulcer
Suppuration
Cellulites
Bacterialinfectionoftheblood
Bacterialinfectionoftheblood:
Bacteraemia
Septicaemia
Pyaemia
pyaemicabscess
septicinfarct
SYSTEMICEFFECTSOF
INFLAMMATION;
Fever
Leucocytosis
ButinthyroidinflammationLeucopeniaisseen
Lymphangitis
ShockduetomassivereleasecytokineandTNF
Disseminatedintravascularcoagulation.
FATEOACUTEINFLAMMATION;
Resolution:
Completereturnrtonormalsituation
oHealingbyscarring:
Excessivetissuedestructionleadstohealing
throughfibrosis
o Suppuration:
Duetopyogenicbacteriaanabscessisformedand
ifitisnotdraineditleadstosepticemia.
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RobinE.RTextbookgeneralpathology,edition3,95124.
HarshMohan.Essentialpathologyfordentalstudents,edition4,89
132
.Munford,R.S.,J.M.Andersen,andJ.M.Dietschy.1981.Sitesof
tissuebindinganduptakeinvivoofbacterialdensitylipoprotein
complexes:studiesintheratandmonkey.J.Clin.Invest.
68:15031513.
Thankyou