炎症与组织细胞损伤的修复 ppt课件

HEALTH DISEASE PEACE WAR 炎症与损伤的修复InflammationandRepair ByDr S J YANGDepartmentofPatholgy 4thMilitaryMedicalUniversity 学习内容 炎症的概念 ConceptionofInflammation 病因 EtiologicAgents 局部表现和全身反应 LocalandSystemicManifestations Signs Symptoms 炎症的基本病理变化 MorphologicPatternsofInflammation 急性性炎症类型及特点 发病机制 AcuteInflammationandPathogenesis 损伤的修复 Repair 慢性炎症及其类型和特点 ChronicInflammation 炎症的结局 PrognosisofInflammation HISTORICALHIGHLIGHTS BigRobbins lists ormighthavelisted CorneliusCelsus ancientRome describedrubor redness calor heat thisappliesonlytotheskin dolor pain andtumor whichthensimplymeant swelling asthe cardinalsignsofinflammation JohnHunter thegreatearlysurgeon 1793 parodiedbyWilliamBlakeas JackTearguts firstcharacterizedinflammationasanonspecificbodyresponse RudolfVirchowaddedfunctiolaesa lossoffunction asthefifthcardinalsignofinflammation andhisstudent JuliusCohnheim providedthebasicstudiesofthepathologicmicroanatomyofinflammation ElieMetchnikoff 1892 wasthefirsttoobserveandstudyphagocytosis ThisisthesameMetchnikoffwhopopularizedyogurtasa healthandlongevityfood Hediedatage70 PaulEhrlichdevelopedtheideaofhumoralimmunityearlyinthiscentury ThisisthesameEhrlichwhodevelopedthe magicbullet forsyphilis andmostofthestainswestilluse ThomasLewisdemonstratedthatinflammationisbroughtaboutbychemicalmediators mostofwhichactlocally Someonemaystillaskyouaboutthe tripleresponseofLewis toasuperficialscratch 1 animmediateredscratchmark 2 aredflarearoundthescratchmark 3 aredswollenarea wheal aroundtheflare Tryit Dr Lewisfoundthathecouldeliminatetheflare butnottheothers bycuttingtheautonomicnervesupply i e preventingthe axonreflex 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 Shock mostcommoningram 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 specificgravity 1 012 Hydrostaticpressure Oncoticpressure Non InflammatoryEdema IncreasedHydrostaticPressure EDEMA TRANSUDATE proteincontentlow specificgravity 1 012 Hydrostaticpressure Oncoticpressure Non InflammatoryEdemaDecreasedOncoticPressure DecreasedOncoticPressure 胶体渗透压 静水压 晶体渗透压 EDEMA EXUDATE proteincontenthigh specificgravity 1 020 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 Serousexudation Serousinflammation Serousexudation Serousinflammation 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 Rolling Adhesion Transmigration 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 Definition FibroplasiaorFibrosis 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 InflammationChronicInflammation Hepatitis 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Mononuclearcells macrophages 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 caseatingGranulom