炎症与组织细胞损伤的修复.ppt

HEALTH(2)aredflarearoundthescratchmark;(3)aredswollenarea(wheal)aroundtheflare.(Tryit!)Dr.Lewisfoundthathecouldeliminatetheflare,butnottheothers,bycuttingtheautonomicnervesupply(i.e.,preventingtheaxonreflex).Thisexperimentledtothediscoveryofhistamine,whichmediatesevents1and3.,InflammationDefinition,各种致炎因子引起机体的组织损伤所诱发的以防御为主的局部组织反应。(第一版）具有血管系统的活体组织对损伤因子所发生的防御反应。（第四版）Inflammationandrepair-Defensivereaction.Defensive?Defective?,DefinitionbyBigRobbins,“Inflammationisthereactionoflivingtissuestoallformofinjury.Itinvolvesvascular,neurologic,humoralandcellularresponseatthesiteofinjury”（BasicPathology）,EtiologicAgentsofInflammation,“Allthefactorsthatcaninjurythetissuesandcellscanalsocauseinflammationofthebody.Theyincludethephysical,chemicalbiological,andImmunologicalagentsetal.”,炎症的致病原因,Localandsystemicmanifestations,AcuteInflammationCardinalSigns(Celsus,1AD),Redness(rubor)Swelling(tumor)Heat(calor)Pain(dolor)Lossoffunction(functiolaesa)(thefifthcardinalsignsupposedlyaddedbyVirchow),AcuteInflammationCardinalSigns-Redness,AcuteInflammationCardinalSigns-Swelling,AcuteInflammationCardinalSigns-Pain,InflammationSystemicManifestationsofInflammation,Fever-clinicalhallmarkofinflammationEndogenouspyrogens:IL-1andTNF-aLeukocytosis-maybeneutrophils,eosinophils,orlymphocytesLeukopenia-rareAcutePhaseReactants-non-specificelevationofmanyserumproteins-willmarkedlyincreasethe“sedrate”,Leukocytosis,LinesofDefense,InflammationSystemicManifestationsofInflammation,Shockmostcommoningram-negativesepticemia(bacteriainthebloodstream),althoughitcanoccurwithgram-positivebacteremiaLipopolysaccharide(endotoxin)ofgram-negativescanproducesymptomsofshockwheninjectedintoanimalsTNF-acanproduceasimilarsyndrome,三、炎症的基本病理变化,基本病变,变质：Alteration,渗出：Exudation,增生：Proliferation,变质和渗出出现于早期，而增生出现于晚期,变质（Alteration）1、概念：炎症局部组织发生的变性和坏死2、原因：致病因子直接作用局部血液循环障碍免疫介导炎症反应产物的间接作用,3、变质的细胞的类型和形态变化,实质细胞,变性：细胞水肿、脂肪变性,坏死：凝固性和液化性坏死,间质细胞,变性：黏液变性、玻璃样变性,坏死：纤维素样坏死,渗出(Exudation)1、概念：炎症局部组织血管内的液体成分、蛋白质和各种白细胞通过血管壁进入组织、体腔、体表和粘膜表面的过程，称为渗出渗出是炎症最重要特征性变化,增生(Proliferation)1、实质细胞增生：肝炎时，肝细胞的再生慢性胆囊炎时粘膜上皮和腺体增生2、间质细胞增生：包括巨噬细胞、血管内皮细胞和成纤维细胞,炎症的类型Classificationofinflammation,临床类型,急性炎症：病程短，几天1月，以变质渗出为主,慢性炎症：病程长，数月数年，以增生为主,OUTCOMESOFINFLAMMATION,IncitingStimulus,AcuteInflammation,Chronic-activeInflammation,ChronicInflammation,Resolution,Abscess,Resolutionwithscarring*,*Thelongerthestimuluspersists,thegreaterthescarringwillbe.,Adynamiccontinuumofchange,Spreading,BacteremiaToxemiaSepticemiaPyemia,Storyofmice,AcuteInflammation,PathogenesisofAcuteInflammationTypeofAcuteInflammation,急性炎症,PHASESOFINFLAMMATIONInitiationAmplificationTermination,急性炎症的类型,病理分类,浆液性炎,纤维素性炎,化脓性炎,出血性炎,InflammationPhasesofAcuteInflammation,Initiation(开始或启动)血管反应为中心Stimulation(injury)withchangesinmicrovasculatureStructuralchangesleadingtoextravasationEmigrationofWBCstothesiteofinjuryAmplification(扩大或进展)*-炎症介质和炎细胞的作用BothsolublemediatorsandcellularinflammatorysystemsareactivatedandamplifiedTermination(终止)*-再生、修复和愈合-accomplishedbyspecificinhibitionordissipationofthemediators,急性炎症的早期反应PhasesofAcuteInflammation-Initiation,Initialvasoconstriction(secondstominutes),followedbyalongerperiodofvasodilationLeakageoffluidandplasmafromtheintravascularcompartment(increasedpermeability)Stasis,withtransmigrationofleukocytesanderythrocytesintoextravasculartissue,TheTripleResponse-SirThomasLewis(1927),Normalregulationoffluidtransport,Extravascularfluid(littleproteinorpressure),Hydrostaticpressure,Oncoticpressure,EDEMA-TRANSUDATE(proteincontentlow-specificgravity1.012),Hydrostaticpressure,Oncoticpressure,Non-InflammatoryEdema,IncreasedHydrostaticPressure,EDEMA-TRANSUDATE(proteincontentlow:specificgravity1.020),Hydrostaticpressure,Oncoticpressure,InflammatoryEdemaIncreasedVascularPermeability,Diapedesis血球渗出,AcuteInflammationPathogenesisofEdema,Non-inflammatoryedema,e.g.:Pulmonaryedemaduetoheartfailure(increasedhydrostaticpressure)Nephroticsyndrome(decreasedoncoticpressure)Inflammatoryedema,either:Direct,irreversibleinjury-allvessels(burns)Transientincreaseinvascularpermeability,i.e.,theeffectofmediatorsonpost-capillaryvenules,浆液性炎,SerousexudationSerousinflammation,SerousexudationSerousinflammation,浆液性炎,Fibrinousexudation,白喉,纤维素性炎,Fibrinousexudattion,白喉,Fibrinousexudattion,绒毛心,Pseudomembranousenterocolitis,假膜性炎,Pseudomembranousenterocolitis,假膜性炎,HemorrhagicInflammation,HemorrhagicFeverwithRenalSyndrome,出血性炎,炎症灶的血管损伤严重，渗出物中含有大量红细胞。不是独立的类型，常与其他类型合并存在，如纤维素性出血性炎常见于流行性出血热、钩端螺旋体和鼠疫等急性传染病。,急性炎症扩展PhasesofInflammation-Amplification,PMNsandmacrophagesarerecruitedtothesiteofinjuryfromperipheralbloodbychemokines,principallyIL-8,plusc5a,TGF-b,andPlatelet-derivedGrowthFactorIL-1andTNFcausethereleaseofpost-mitoticreservegranulocytesfromthemarrow,plusinducetheproductionofColonyStimulatingFactors(CSF),Exudationofbloodcells,InflammationNeutrophil,InflammationNeutrophilGranules,Primary-containserineproteases,lysozymeandphospholipaseA2Secondary-similartoprimary,butalsocontainlactoferrinandcollagenaseTertiary-presentattheleadingedgeofmigratingPMNs,containgelatinasesthatarecapableofdegradingbasementmembrane,InflammationEosinophil,InflammationMONONUCLEARPHAGOCYTES,InflammationLymphocyte,InflammationPlasmacell,白细胞游出LeukocyteExtravasation,Margination,rolling,andadhesionTransmigration(diapedesis)Migrationtowardthesiteofinjuryalongachemokinegradient,Sequentialinvolvementofadhesionmolecules,CentralAxialStream,RollingAdhesionTransmigration,SELECTINS(E&P),INTEGRINS&Ig-LIKEMOLECULES(ICAM,VCAM),QualitativeandQuantitativeEndothelialandPMNChanges,InflammationAdhesionMoleculeModulation,P-selectinisredistributedtothecellsurfacefromtheWeibel-Paladebodiesduetostimulationbythrombin,histamine,andPlateletActivatingFactor(PAF)InductionofE-selectinonendotheliumbyIL-1andTNFIncreasedavidityofbindingofintegrins(conformationalchange),InflammationMarginationandPavementing,InflammationTransmigration,趋化作用Chemotaxis,Exogenousmediators,e.g.:N-formylmethionineterminalaminoacidsfrombacteriaLipidsfromdestroyedordamagedmembranes(includingLPS)Endogenousmediators,e.g.:Complementproteins(C5a)Chemokines,particularlyIL-8Productsoflipoxygenase(LTB4),炎细胞的作用InflammatoryCellFunction,PhagocytosisopsonizedbyIgG(subtypes1or3)orC3bLocalimmuneresponsebymonocytesandlumphocytesaswellascytokinesTissueinjurybyinflammatorycellsthoughtheproteinaseandinflammatorymediators,吞噬作用、免疫作用、引起组织损伤,InflammationMononuclearPhagocytes,Neutrophilingestionofbacteria,gramstain,炎症介质ChemicalMediatorsofInflammation,VasoactiveaminesComplementsystemKininsystemCoagulationpathwayFibrinolyticpathwayArachodonicacidmetabolitesPlateletactivatingfactorCytokinesNitricoxide,-以中性粒细胞渗出为主，并伴有不同程度的组织坏死和脓液形成。脓液：为脓性渗出物，外观呈浑浊的凝乳状液体，灰黄色或灰白色，稀薄或粘稠脓液的成分：脓细胞、细菌、坏死组织、浆液脓细胞：为变性坏死的中性粒细胞。,化脓性炎中性白细胞渗出Purulentinflammation-ExudationofNeutrophil,(1).表面化脓和积脓表面化脓-指发生于粘膜或浆膜的化脓性炎,黏膜的化脓性炎又呈脓性卡他性炎如化脓性尿道炎，中性白细胞向黏膜表面渗出，深部组织不明显.积脓-当化脓性炎发生于粘膜或浆膜时，脓液积聚于浆膜腔、胆囊和输卵管腔内.(2).脓肿(3).蜂窝织炎（phegmonousinflammation）疏松结缔组织的弥漫性化脓性炎，常发生于皮肤、肌肉和阑尾。,溶血性链球菌,透明质酸酶降解结缔组织基质中的透明质酸,链激酶溶解纤维素,Acutemeningitis-Purulentexudate,表面化脓,Acutesalpingitis-Purulentexudate,积脓,Acutesalpingitis-Purulentexudate,Abscesss,脓肿,InflammationTissueInjurybyInflammatoryCells,脓肿,InflammationAcuteInflammatorycellinfiltration,弥漫性化脓,ActivatedoxygenspeciesCanmigratethroughintactplasmamembranesInitiatelipidperoxidationReactwithDNAOxidizesulfhydrylgroupsofproteinsDegradeextracellularmatrixcomponents,炎症引起组织损伤TissueInjurybyInflammatoryCells,炎症引起组织损伤TissueInjurybyInflammatoryCells,LysosomalenzymesSincetheseenzymesareusedtodegrademicroorganismsinlysosomes,obviouslytheycoulddamagetissueintheextracellularenvironmentUsuallyproteaseactivityiscontrolledbyavarietyofanti-proteasespresentinplasma(a1-anti-trypsin,a2-macroglobulin,etc.),炎症引起组织损伤TissueInjurybyInflammatoryCells,PhagocyticcelladherenceAdherencetobasementmembranes,othercomponentsoftheextracellularmatrixandothercellsbyphagocytesenhancesthedamagecausedbyreactiveoxygenspeciesandlysozyme,becausenormalinhibitorspresentinplasmacannotgainaccesstothatspacebyvirtueofthephagocyticcelladherence,炎症引起组织损伤TissueInjurybyInflammatoryCells,Therelativelyprimitiveandnon-specificimmuneeffectsofpolymorphonuclearleukocytesandmacrophagesuponinvadingmicroorganismsarealsocapableofdamagingthehostbytheextracellularreleaseofenzymesandactivatedoxygenspecies,InflammationTissueInjurybyInflammatoryCells,InflammationTyphoidalulcers,InflammationTissueInjurybyInflammatoryCells,损伤的修复TissueRepair,损伤的修复与愈合Regeneration,RepairandHealing,修复（repair）：损伤造成机体部分细胞和组织丧失后，机体对所形成缺损进行修补恢复的过程，称为修复。,方式,再生性修复,由周围同种细胞增生修复纤维性修复,由肉芽组织填补,再生（Regeneration）：是指由同种细胞分裂增生来补充机体老化、消耗或坏死的细胞的过程。可分为：生理性再生：也称为完全性再生。是指生理过程中老化、消耗的细胞由同种细胞分裂增生补充，如表皮角化层经常脱落，由表皮基底细胞增生、分化，予以补充。病理性再生：也称不完全再生。是指病理状态下，组织细胞损伤后发生的再生，一般由纤维组织增生代替。,再生修复RepairbyRegeneration,Definition-Regeneration,Regenerationisatypeofrepair.Thebestexampleofhealingbyregenerationinhumansoccursintheliver,whichhasincredibleregenerativeproperties.Itispossibletoresectvirtuallyanentirelobeofliver,andtheorganwillrepairitselfoveraperiodofmonthstocompletelyrecapitulateitspreviousstructure.,（1）不稳定细胞（Labilecells）再生能力最强，如全身的上皮细胞、淋巴造血细胞等。（2）稳定细胞（Stablecells）损伤后，有较强再生能力。如肝、胰、内分泌腺等腺上皮，成纤维细胞、血管内皮细胞、骨细胞和原始间叶细胞等，平滑肌细胞也属稳定细胞，但再生能力弱。（3）永久性细胞（Permanentcells）几乎没有再生能力，受损伤后由结缔组织增生修补，如神经细胞、心肌细胞及骨骼肌等。,细胞的再生能力Classificationofcellsbytheirproliferativepotential,Cellclassification,Labilecells:Thissub-populationofcellsisconstantlyturnedover.Thebestexamplesarefoundintheepithelialcellpopulationoftheskinorgut,andthehematopoeticcellsofthebonemarrow.Thesecellshaveashort,finitelifespan,dieviaapoptosis,andarerapidlyreplaced.,Cellclassification,Stablecells:Stablecellsareasub-populationofcellsthatarenormallyreplacedveryslowly,butarecapableofrapidrenewalaftertissueloss.Hepatocytesandtheproximalconvolutedtubulecellsofthekidneyaregoodexamples.,Cellclassification,Permanentcells:Permanentcellsarefoundinthecentralnervoussystemandheart.Oncetheyaredestroyed,theycannotregenerate.Peripheralnervecellsarecapableoflimitedregenerationhasbeendemonstrated,but,forallpracticalpurposes,thoseoftheCNSarepermanentcells.,损伤的修复WoundHealing-Chickenpox,REGENERATION再生,ATN,regenerative(polyuric)phase.,Hyperplasia增生,Chroniculcerativecolitiswithcryptabscesses,SquamousMetaplasia化生UterineCervix,Dysplasia,cervix不典型增生,损伤的纤维性修复Repairbyconnectivetissue,WoundHealing,RepairGranulationtissueistheinitialresponsetoaninjury,andconsistsofrichlyvascularconnectivetissuewhichcontainscapillaries,youngfibroblasts,andavariableinfiltrateofinflammatorycellsDonotconfusewithGRANULOMA,DefinitionFibroplasiaorFibrosis,Fibrosisisaalsoatypeofrepair.Thebestexampleofhealingbyfibrosisinhumansoccursintheheart,whichcontainspost-mitoticmyocytes.Necrotic(dead)myocytesarealwaysreplacedbycollagenousscarlaiddownbyfibroblasts,sincetheyareincapableofregeneration.,WoundHealingbyFibrosis,InductionofanacuteinflammatoryresponseFormationofnewbloodvessels(angiogenesis)MigrationandproliferationofbothparenchymalandconnectivetissuecellsSynthesisofextracellularmatrixproteinsRemodeling,WoundHealingbyFibrosis,RepairTheorderlyprocessbywhichawoundiseventuallyreplacedbyascarDestructionofepitheliumonlyistermedanerosion,andhealsexclusivelybyregenerationIfdestructionofthebasementmembraneoccurs(extracellularmatrix),thenascarwillform,Healinginspecifictissues(Skin),Definition-Healing,Healingisaresponsetotissueinjury,andrepresentsanattemptbytheorganismtomaintainnormalstructureandfunction.Itoverlapstheinflammatoryprocess.,愈合（Woundhealing）：是指组织遭受创伤进行再生修复的过程。,WoundHealing,Primaryintention:theusualcasewithasurgicalwound,inwhichthereisacleanwoundwithwell-apposededges,andminimalclotformationSecondaryintention:whenwoundedgescannotbeapposed,(e.g.,followingwoundinfection),thenthewoundslowlyfillswithgranulationtissuefromthebottomupAlargescarusuallyresults,TissueRepairPhasesofWoundHealing,Factorsthatinfluencewoundhealing,Type,size,andlocationofthewound(determinesprimaryorsecondaryintention)Vascularsupply(diabeticshealpoorly)Infection-delayswoundhealingandleadstomoregranulationtissueandscarringMovement-woundsoverjointsdonothealwell,duetotractionRadiation-ionizingradiationisbad,UVisgood,Factorsthatinfluencewoundhealing,Overallnutrition:vitaminandproteindeficienciesleadtopoorwoundhealing,especiallyvitaminC,whichisinvolvedincollagensynthesisAge:youngerisdefinitelybetter!Hormones-corticosteroidsimpairwoundhealing,becauseoftheirprofoundeffectoninflammatorycells,ComplicationsofWoundHealing,DefectivescarformationExcessivescarformation(keloid)Contraction,ComplicationsofWoundHealing,DefectivescarformationDehiscenceorulcerationisusuallydueto:Woundinfection(common)Malnutrition(scurvy-rare)Hypoxiawithulceration,usuallyduetoinadequatevascularityintheskinflap(common),ExcessiveScarFormation,Excessivescarformation(keloid).Keloids(hypertrophicscars)aretheresultofover-exuberantproductionofscartissue,whichisprimarilycomposedoftypeIIIcollagen.Thecauseisthoughttobeduetogeneticfactors,perhapsduetolackofthepropercollagenasestodegradetypeIIIcollagen.Contraction,Keloid,Keloid(micro),Contraction,Excessivecontractionofawoundisknownasacontracture.TheyareaspecialprobleminthetreatmentofextensiveburnsSeveraldiseasesofunknowncausearecharacterizedbytheformationofcontracturesPeyroniediseaseofthepenisDupuytrendiseaseofthepalms,Healinginspecifictissues(heart),Cardiacmyocytesarepermanentcells.Theydonotdivide,andtheheartthushealsbyresolution(deadmyocytesarephagocytizedbymacrophages)andcollagenousscarformation.,AcuteMI(gross),AcuteMI(micro),RemoteMI(micro),Healinginspecifictissues(liver),Theliverhealsbyregeneration.Itcanregenerateperhaps75%ofitsvolume.Scarringoccurswhentheextracellularmatrixoftheliverisdamagedbyrepeatedorsevereinjury.Bileductsthenproliferate,regenerativenodulesform,andcollagenousscarsbecomeevident.Thisscarringprocessiscommonlycalledcirrhosis.,InflammationChronicInflammationHepatitis,Cirrhosis,trichrome,Healinginspecifictissues(Bone),ChronicInflammation,慢性炎症,InflammationChronicInflammation,Chronicinflammationmayoccurasasequeltoacuteinflammation,orasaprimaryimmuneresponsetoaforeignantigen(usuallyviral)Typeofchronicinflammationincludes:general,granulomatousinflammation,Inflammatorypolypandpseudotumor,ACUTE,CHRONIC,Vascularchanges,Cellularinfiltrates,Stromalchanges,VasodilationandIncreasedpermeability,PolymorphsNoreplication,Minimal-separationduetoedema,Minimal,MononuclearReplication,CellularproliferationFibrosis,InflammationCharacteristicsofacuteandchronicinflammation,Inflammation慢性炎症(ChronicInflammation),病变特点Histologicfeatures慢性炎细胞浸润和组织细胞增生Mononuclearcellsmacrophages,lymphocytes,andplasmacells.组织结构破坏和瘢痕修复Tissuedestructionbyongoinginflammation,thoughttobeduetocytokinesproducedlocallybythemononuclearcells.上皮细胞增生、化生和不典型增生hyperplasia,metaplasiaandanaplasiaofparrenchymalcells.,InflammationChronicInflammation,Monocyte/MacrophagesKeycellinchronicandgranulomatousinflammationReproducelocally,atthesiteofinjuryProducenumerouscytokines,whichcontinuetorecruitadditionalcells,includingmoremacrophagesMaypresentantigentoT-cells,producingspecifichypersensitivityreactions,ChronicInflammatoryInfiltrate,InflammationGranulomatousInflammation,AcellularmechanismfordealingwithindigestiblesubstancesTheprincipalcellsinvolvedingranulomatousinflammationaremacrophagesandlymphocytesEpithelioidhistiocytesarethehallmarkofgranulomatousinflammation,InflammationGranulomatousInflammation,Immunitymaybejudgedbyitseffectontheinvadingorganism,butanadverseeffectonthehostisgenerallytermedhypersensitivityDestructionoftissueisprimaryviatheactionofkillerTcells,directedbymacrophagesTheoldtermfortuberculosiswasconsumption,forgoodreason,GranulomatousInflammation,Langhanstypegiantcells,MultinucleatedGiantCells,Epithelioidcells,InflammationGranulomatousInflammation,Tuberculouslung,InflammationGranulomatousInflammation,TuberculousGranuloma,InflammationGranulomatousInflammation,Foreignbodygiantcellsinsuturegranuloma,InflammationGranulomatousInflammation,CaseatingGranuloma,Non-caseatingGranuloma,CaseousNecrosis,Macrophages,EpithelioidCells,andGiantCells,Lymphocytes,Fibroblasts,Sarcoidosis,InflammatoryPolyp,InflammatoryPolyp,InflammationInflammatorypseudo