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INFLAMMATION

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&macrophages
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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