中國醫(yī)科大學(xué)病理學(xué)英文課件6

Chapter4.InflammationZhaoYueSection1.Introduction

1.Definition:

1)Inflammation:adefensivereactioninlivingtissuewithvascularsystemtoinjuriousstimuli.2)ReactionofBVsisthecentrallinklimitingandkillinginjuredfactoreliminatingandabsorbingnecrotictissue3)Theinflammatoryresponsesiscloselyintertwinedwiththeprocessofrepair4)Significance(1)Beneficial

:withoutinflammationInfectionswouldgouncheckedinjuredorgansmightremainpermanentfesteringsores

woundwouldneverheal(2)Harmful:

hypersensitivereactionstodrugs,toxinsunderliecommonchronicdiseases→rheumatoidarthritis,atherosclerosis,andlungfibrosisfibrousrepair→disfiguringscarsorfibrousbandsthatcauseintestinalobstructionorlimitthemobilityofjoints.2.Causesofinflammation1.Biologicfactors: bacteria,Virus,fungi,parasites→themostcommon2.ChemicalfactorsExogenous:drugs,acidEndogenous3.Physicalagents:trauma,burn4.Allergicreaction:GN,TB

lupus3.Basicpathologicchanges1.Alteration

Degeneration,necrosisoflocaltissueandcellsParenchymalCcellularswellingfattychangecoagulative,liquefactivenecrosisMesenchymalCmucoidchangeamyloidchangefibrinoidnecrosishyalinechange2.Exudation:

Ininflammatoryfoci,theescapeoffluid,proteins(fibrin),bloodcellsfromvascularwallintointerstitialtissue,bodycavitiesorsurfaceofthebodyandmucosa3.Proliferation

Parenchymal:epithelium,hepatocyteMesenchymal:fibroblast,EC,histocyte

4.Clinicaltypes1)Acuteinflammation(1)Relativelyshortduration,lastingforafewdaysorafewweeks(2)Lesionsexudationoffluid,neutrophilsdegeneration,necrosis2)Chronicinflammation(1)longerdurationforafewmonthsoryears(2)LesionsProliferation:BV,fibrosisLC,PC,Macrophageinfiltration病例六病史：男性，40歲，頸部患“癤”，紅、腫、熱、痛，10天后局部紅腫發(fā)展至手掌大，體溫38℃，局部手術(shù)切開引流。當(dāng)晚即惡寒、高熱、頭痛，次日體檢發(fā)現(xiàn)病人輕度黃疸，肝脾腫大，體溫39℃，WBC計數(shù)21.0G/L。思考題：用所學(xué)的炎癥知識，作出病理診斷并解釋上述臨床表現(xiàn)。Section2.AcuteinflammationTwomajormechanismsofhostdefense:AntibodyLeukocytesmajorcomponents:1)Changesofhemodynamics

2)Fluidexudation3)LeukocyteextravasationandphagocytosisagainstmicrobesI.Changesofhemodynamics1.Alterationinvascularflowandcaliber

1)Transientvasoconstrictionofarterioles:lastingforafewseconds.2)Vasodilationandincreasedbloodflow(1)Arteriolardilationopeningofnewcapbedsincreasedbloodflowinflammatoryhyperemia(2)Relatedtothefactorsof:Bodyfluid:chemicalmediatorNervous:axonreflection3)Slowingofbloodflow:increasedpermeabilityofthemicrovasculatureoutpouringoffluidintoextracellulartissuesconcentrationofRBCandincreasedviscosityofbloodstasisofbloodflowNormalbloodflowVasodilationincreasedbloodflowSlowingofbloodflowStasisofbloodflowExtravasation(fluidandleukocyte)2.IncreasedvascularpermeabilityIncreasedpermeability→themostimportantcauseresultinginexudationoffluidandprotein

MechanismofIncreasedpermeability1)ECretraction

FormationofendothelialgapsinvenulesImmediatetransientresponse:occursrapidlyafterexposuretothemediatorandisusuallyreversibleandshort-lived(15to30minutes)mostcommonmechanismofvascularleakageandiselicitedby:histamine,bradykinin,substanceP,leukotriene2)CytoskeletalreorganizationDelayedprolongedresponseinducedbycytokines(IL-1,TNF,IFN-γ),increasedpermeabilityafteradelayof4to6hourslastingformorethan24hoursinvolvesvenulesaswellascap.theendothelialcellsretractfromoneanother3)IncreasedtranscytosisacrosstheendothelialcytoplasmBytranscytoplasmicchannelVEGF,histamine,bradykinin,Increasingthenumberandthesizeofchannels4)DirectendothelialinjuryImmediatesustainedresponse:

severeburn,purulentBacteriaresultinECnecrosisanddetachmentleakagestartsimmediatelyafterinjurysustainedatahighlevelforseveralhoursuntildamagedBVthrombosedandrepaired5)Leukocyte-mediatedendothelialinjuryMild-to-moderatethermalinjury,toxin,x-radiatonincreasedleucocyteinfiltration

involvesvenulesaswellascap.LeukocyteadheretoECactivatedReleasingtoxicspeciesandproteolyticenzymes6)Highpermeabilityofnewcapsduringrepair,endothelialcellsproliferateandformnewbloodvessels①NewvesselssproutsremainleakyuntilECsdifferentiateandformintercellularjunctions.②Certainfactorsthatcauseangiogenesis(VEGF)increasepermeability③Increaseddensityofreceptorforvasoactive

mediatorsinthesurfaceofECDiagrammaticrepresentationoffivemechanismsofincreasedvascularpermeabilityininflammationII.Fluidexudation1)Majorcauses:①Increasedvascularpermeability→escapeofaprotein-richfluidintotheinterstitium②Thelossofprotein

reducesintravascularcolloidosmoticpressureincreasesthecolloidosmoticpressureoftheinterstitialfluidBloodpressureandplamacolloidosmoticforcesinnormalandinflammedmicrocirculation.exudation:Theescapeoffluid,proteins,andbloodcellsfromthevascularsystemintotheinterstitialtissueorbodycavities.

Exudate:aninflammatoryextravascularfluidthathasahighproteinconcentration,cellulardebris,andahighergravity.Itimpliessignificantalterationinthenormalpermeabilityofsmallbloodvesselsintheareaofinjury.Transudate:afluidwithlowproteincontent(mostofwhichisalbumin)andalowergravity.Itisessentiallyanultrafiltrateofbloodplasmathatresultsfromosmoticorhydrostaticimbalanceacrossthevesselwall.2)Distinguishbetweenexudateandtransudate

TransudateExudateVascularpermeabilityNormalIncreasedProteinconcentration<30g/L>30g/LProteintypeAlbuminKindsofproteinRivaltatestNegative(-)Positive(+)FibrinNoHaveSpecificgravity<1.018>1.018Cellnumber<300×106/L>1000×106/LAutoagglutinationNoYesAppearanceClear

Cloudy3)Functionsofexudate:(1)Dilutelocaltoxins→reducetheinjurytotissue(2)Bringinthenutritionalsubstanceforleukocytescarryoffthemetabolicproductsininflafoci(3)killthepathogen:Ab,complement(4)Fibrinmesh:limitthespreadingofpathogenicorganismslimittheremovingofMφIII.Leukocyteextravasation

andphagocytosis1)Leukocyteextravasation:leukocytepassthroughvascularwallintothesiteofinjury.

Dividedintofollowingsteps:

MarginationandrollingAdhesionTransmigrationandchemotaxis

(1)Marginationandrolling

leukocyteincentralaxialcolumnBVdilation,speedofbloodflow↓marginationrollingpavementingappearanceLeukocyticemigration

(2)Adhesion:a.Bybindingofcomplementaryadhesionmoleculesontheleukocyteandendothelialsurfacesb.Adhesionmolecules:

Theimmunoglobulinfamily:I(V)CAM-1Integrinsselectinsc.Mechanismsofadhesiveprocess:i)Redistributionofadhesionmoleculestothecellsurface:

Forexample:P-selectin

NormallypresentinW-PbodyofECHistaminethrombin,PAFRedistributedtothecellsurfaceBindingtothereceptorofleukocyteii)InductionofadhesionmoleculessynthesisSomeinflammatorymediators,(IL-1,TNF)inducedthesynthesisandsurfaceexpressionofendothelialadhesionmoleculesForexample:InnormalECNoexpressionofE-selectinIL-1TNFSynthesisandexpressE-selectiniii)IncreasedavidityofbindingForexample:

LFA-1

Presentonneutrophils,monocyte,LCNotadheretoitsligandICAM-1onECowingtoleukocyteactivationLFA-1convertedfromastateoflow-affinitybindingtohighaffinitybinding

towardICAM-1Regulationofendothelialandleukocyteadhesionmolecules.A,RedistributionofP-selectin.B,Cytokineactivationofendothelium.C,Increasedbindingavidityofintegrins(3)Transmigrationandchemotaxis①Injuredvenulesorcaps,leukocytesinsertpseudopodsintojunctionbetweenECssqueezethroughinterendothelialjunctionssecretecollagenase→decomposetheBMescapeintointerstitialtissuepseudopodAdhensionandtransmigration②Redcelldiapedesis:

apassiveprocess,determineinjuredextent③Thetypeofleukocytevarieswiththeageofinflammatorylesion:i)Acute:neutrophilspredominateduringthefirst6~24hs;arereplacedby

monocytein24~48hsii)Chronic:

LC,PC,monocyteLCPCNeutrophilsMCBasophil12-15μmEosinophil12-15μmNeutrophil12-15μmMonocyte14-20μmLmphocyte6-8μmRBC7.5μm④Thetypeofemigratingleukocytevarieswiththetypesofstimulus:i)Viralinfection:LC→firstCtoarriveii)HypersensitivityreactionParasiteinfectioniii)Bacterialinfection:neutrophilsEosinophils⑤Chemotaxis:afterextravasationleukocytesemigratetowardthechemicalmediatorsalongachemicalconcentrationgradient.

Chemotacticagent:

Exogenous:bacterialproductsEndogenous:complements(C5a)leukotrieneB4(LTB4)cytokines:chemokineChemotaxis(4)Therolesofleukocytes

Acriticalfunctionofinflammationistodeliverleukocytestothesiteofinjuryandtoactivatetheleukocytestoperformtheirnormalfunctionsinhostdefense.

Phagocytosis(ingestoffendingagents)Immunologicalfunction(killbacteriaandothermicrobes,andgetridofnecrotictissueandforeignsubstances)Leukocyte–inducedtissueinjury

Phagocytosis:Leukocyteemigratetoinflammatoryfocusengulfandkillordegradatethepathogenicorganismandtissuedebris.a.Typesofphagocytes①Neutrophils:10~12umi)Azurophilicgranules:NeutralproteinaseandacidichydrolaseDigestanddegradatedebris,deadbacteriaMyeloperoxidase,phospholipaseA2,lysozyme,andcationprotein→killthebacteriaii)Specificgranules:Lysozyme,lactoferrin,Alkaliphosphatase,phospholipaseA2②Macrophage:12~24umi)SitedistributedinCT,liver(kupfferC)spleen,LN,lunginflammatoryfocus:derivedfrombloodmonocytekillbacteriaii)Functions:

Phagocytosis→eliminatethedeadbacteria,cells,debris,foreignbodiesthatcan’tbedigested

b.Processofphagocytosis:Involvesthreesteps:

RecognitionandattachmentEngulfmentkillingordegradation①Recognitionandattachment:i)Opsonins:akindofproteininserumwhichenhancestheefficiencyofphagocytosisii)Opsonization:microorganismcontactwiththeserumcontainedopsoninsandarecoatediii)MajoropsoninsFcfragmentofIgGC3b

collectins②EngulfmentBindingofopsonizedparticletotheFcreceptorofphagocyticleukocytePseudopodstocreateadeeppocketcompleteenclosureoftheparticlewithinaphagosomecreatedbytheplasmamembraneofthecellThelimitingmembraneofthisphagocyticvacuolethenfuseswiththelimitingmembraneofalysosomalgranuleresultingindischargeofthegranule'scontentsintothephagolysosome.ProcessofphagocytosisOpsonizationattachmentEngulfmentPhagosomephagolysosomePhagocytosisofaparticle(e.g.,bacterium)involvesattachmentandbindingofFcandC3btoreceptorsontheleukocytemembrane,engulfment,andfusionoflysosomeswithphagocyticvacuoles,followedbydestructionofingestedparticleswithinthephagolysosomes.③killingordegradation:i)Phagolysosome→releasemanyenzymesii)Killingisaccomplishedlargelybyoxygen-dependentmechanismThegenerationofreactiveoxygenintermediatesisduetotherapidactivationofNADPHoxidase,whichoxidizesNADPHand,intheprocess,reducesoxygentosuperoxideanion.Superoxideisthenconvertedintohydrogenperoxide(H2O2).TheH2O2generatedbytheNADPHoxidasesystemisgenerallynotabletoefficientlykillmicrobesbyitself.Theazurophilicgranulesofneutrop