醫(yī)學精品課件：3炎癥2016

炎癥InflammationNANJINGMEDICALUNIVERSITY李蕓茜lyq_52245@163.comaprotectiveresponseinvolvinghostcells,bloodvessels,andproteinsandothermediatorsthatisintendedtoeliminatetheinitialcauseofcellinjury,aswellasthenecroticcellsandtissuesresultingfromtheoriginalinsult,andtoinitiatetheprocessofrepair.

WhatisInflammation?機體的保護性反應(yīng)目的：①清除引起損傷的因素

②清除壞死組織參與者：血管，血液，白細胞…炎癥的概念什么時候會有炎癥反應(yīng)？機體為什么要清除損傷因素和壞死組織？如果炎癥反應(yīng)：①異常發(fā)生inappropriate

②過于強烈toostrong

③持續(xù)時間過長prolonged

為啥要吃消炎藥？炎癥過程伴隨正常細胞損傷與慢性病和癌癥有關(guān)致炎因子感染Infection壞死Tissuenecrosis

異物Foreignbodies(ex&en)免疫反應(yīng)ImmunereactionsIschemiaTraumaChemicalinjuryPhysicalinjury炎癥的步驟識別致炎因子和壞死組織招募白細胞

清除致炎因子和壞死組織修復(fù)調(diào)控發(fā)生于過程炎癥的基本病理變化變質(zhì)滲出增生exudation滲出液成分Leukocytes:Neutrophils(PMNs)Monocytes(macrophages,M?)LymphocytesPlasmacellsEosinophilsPlasmaproteins:AlbuminsGlobulinsComplementFibrinogenFibrins細菌屏障修復(fù)支架exudates炎癥的局部表現(xiàn)紅、腫、熱、痛、功能障礙Aeromonashydrophilainfectionfollowingpuncturewithfishinghook皮膚蜂窩織炎cellulites慢性腎小球腎炎炎癥類型：急性與慢性急性炎癥Acuteinflammation持續(xù)時間短中性粒細胞浸潤

滲出明顯慢性炎癥Chronicinflammation持續(xù)時間長單個核細胞浸潤（巨噬C，淋巴C，漿C）組織增生修復(fù)明顯急性炎癥與慢性炎癥比較FeatureAcuteChronicOnsetFast:minutesorhoursSlow:daysCellularinfiltrateMainlyneutrophilsMonocytes/macrophagesandlymphocytesTissueinjury,fibrosisUsuallymildandself-limitedOftensevereandprogressiveLocalandsystemicsignsProminentLessprominent;maybesubtle

急性肺炎慢性肺炎

血流增加蛋白滲出PMNs游出把蛋白和白細胞送至損傷處

急性炎癥急性炎癥過程分解血管變化Vascularchanges

血流動力學改變

hyperemia通透性增加

leakage

白細胞事件Cellularevents

白細胞招募

recruitment

白細胞殺傷和清除activationinflammatorymediatorsDilationofarteriolesOpeningupofcapillaries充血①細動脈短暫收縮Gaps②漏出液Transudate③滲出液Exudate1Proteins③充血和通透性增加導(dǎo)致：水腫edema/積液effusion血流停滯satsis

白細胞邊集marginationTransudatesCrossesintactmembraneMostclear(acellular)CausedbyhydrostaticimbalanceorosmoticgradientsExudatesCrossesthroughgapsincapillaryMostcloudy(cellular)CausedbyinflammationEdemacanbecausedbyexudatesortransudatesPericardialEffusion:ExudateVersusTransudate

ExudateTransudateEtiologyMalignancy

Infectious

Postpericardiotomysyndrome

CollagenvasculardiseasesRadiation

Uremia

Hypothyroidism

TraumaSpecificgravity(g/mL)>1.015<1.015Totalprotein(g/dL)>3.0<3.0Fluid/serumproteinratio>0.5<0.5Fluid/serumLDHratio>0.6<0.6Fluid/serumglucoseratio<1.0>1.0LDH=lactatedehydrogenaseRetractionofendotheliumEndothelialinjury血管通透性增加的機制血管通透性增加的機制內(nèi)皮收縮內(nèi)皮損傷

IncreasedtranscytosisofproteinsLeakagefromnewbloodvessels

Immediatetransientresponsedelayedprolongedleakage

Immediatesustainedleakage

滲出液？漏出液？滲出液？漏出液？

肝硬化病人伴腹水滲出液？漏出液？淋巴系統(tǒng)在炎癥中的作用Helpsdrainedemafluid,leukocytes,andcelldebrisMaytransporttheoffendingagent(especiallymicrobes)lymphangitislymphadenitislymphangitisduetoTrypanosomiasistsetseflylymphadenitisduetotularemiaGroinArmpitNeckUnderthejawandchinBehindtheearsOnthebackofthehead

Commonareaswherethelymphnodescanbefeltinclude:

細胞事件：招募與激活通常只發(fā)生在需要的時間和地點…白細胞：①得到通知②停下③出血管④向正確的方向行走…白細胞招募

recruitment滾動rolling

粘附adhesion

游出transmigration

趨化作用chemotaxis血管內(nèi)跨血管血管外Thejourneyofleukocytesismediatedandcontrolledbyadhesionmoleculesandchemokines.粘附分子趨化因子EndothelialMoleculeLeukocyteMoleculeMajorRoleP-selectinSialyl-LewisX-modifiedproteinsRolling(neutrophils,monocytes,lymphocytes)E-selectinSialyl-LewisX-modifiedproteinsRollingandadhesion(neutrophils,monocytes,Tlymphocytes)GlyCam-1,CD34L-selectinRolling(neutrophils,monocytes)*ICAM-1(immunoglobulinfamily)CD11/CD18integrins(LFA-1,Mac-1)Adhesion,arrest,transmigration(neutrophils,monocytes,lymphocytes)VCAM-1(immunoglobulinfamily)VLA-4integrinAdhesion(eosinophils,monocytes,lymphocytes)CD31CD31Transmigration(allleukocytes)趨化因子chemoattractants趨化作用Chemotaxislocomotionalongachemicalgradient趨化因子（bestidentified）SolublebacterialproductsComplementcomponentsC5aChemokines(IL-8,MCP-1)LTB4(AAmetabolite)白細胞游出Transmigrationdiapedesis白細胞血管外阿米巴樣運動不同場合聚集的白細胞種類不同…與炎癥反應(yīng)的階段有關(guān)

（theageoftheinflammatoryresponse）中性粒細胞PMNs單核/巨噬細胞Monocytes/macrophges6hr24hr48hr72hr不同場合聚集的白細胞種類不同…與致炎因子種類有關(guān)（thetypeofstimulus）萄球菌、鏈球菌

嗜中性粒細胞病毒

淋巴細胞過敏性反應(yīng)

嗜酸性粒細胞蠕蟲感染

嗜酸性粒細胞MyocardiuminfarctDay1Day3病毒性腦炎哮喘Asthma白細胞激活Sense到死細胞和微生物的存在吞噬phagocytosis細胞內(nèi)殺傷和降解細胞外捕捉“traps”生產(chǎn)炎癥介質(zhì)TLRsinflammasome調(diào)理素受體吞噬PhagocytosisReactiveOxygenSpecies(ROS)NitricOxide溶酶體中的酶和蛋白

細胞內(nèi)殺傷及降解機制oxidativeburstdefensinslysozymelactoferrincathelicidinsMajorbasicproteinNeutralproteaseAcidproteaselysosomalgranules…Degrade&killing

phagocyteAlongfibreLeakedenzymes

殺菌物質(zhì)被釋放到細胞外…Emphysema肺氣腫duetoα1-antitrypsindeficiencyNeutrophilextracellulartraps(NETs)

Healthyneutrophils被困之鏈球菌細胞外殺傷機制白細胞介導(dǎo)的組織損傷"bystander"tissuesAutoimmunediseasesAllergiesIschemiareperfusionreleaseoflysosomal

granulecontents巨噬細胞激活后的功能Phagocytose

pathogensanddyingcellsProducecytokines

toamplifyorlimitinflammatoryreactionsProducegrowthfactorsendothelialcellsfibroblastscollagensynthesisPresentingantigenDefectsinleukocyteadhesionLAD-1LAD-2Defectsinmicrobicidalactivity

ChronicgranulomatousdiseaseDefectsinphagolysosomeformation

Chédiak-Higashisyndrome先天性白細胞功能缺陷CGD獲得性白細胞功能缺陷放射性治療Radiationinjury癌癥治療Cancertherapy糖皮質(zhì)激素Glucocorticoidadministration糖尿病Diabetes酗酒Alcoholism感染的擴散和蔓延局部蔓延淋巴道蔓延血行蔓延菌血癥toxemia毒血癥septicemia敗血癥septicemia膿毒血癥pyemiaSummary:Acuteinflammationrapidlydelivers…and…tositesofinjurythemainvascularreactionsare…and…theresultingfluidaccumulationiscalled…aftertheendothelialcellsgetthesignalfrom…,theyandleukocytesupregulatetheexpressionof…tofacilitatethemovementsofleukocytesthatinclude………and……predominateintheearlyinflammatoryinfiltrateandarelaterreplacedby….themainjobsofleukocytesatsiteare…and…themostpowerfulweaponstokilliscalled…ownedby…acuteinflammationoftencauseunwanteddamagebecause…theoutcomesmaybe…,…or…Summary:Acuteinflammation炎癥介質(zhì)

MediatorsThemostimportantmediatorsofacuteinflammationare:Vasoactiveamines(histamine)Lipidproducts(prostaglandins&leukotrienes)

Cytokines(includingchemokines)Complementproductsthesubstancesthatinitiateandregulateinflammatoryreactions來源Sources:細胞釋放血漿蛋白中前體激活MajorlybythesentinelsOthers:PMNs,Plts,endothelium,epithelium炎癥介質(zhì)

Mediators有活性的炎癥介質(zhì)只在相應(yīng)的刺激下生成

大部分短命一種介質(zhì)可刺激其他介質(zhì)釋放

擴張細動脈，增加細靜脈通透性

Histamine儲存在肥大細胞顆粒中，受刺激迅速釋放

引起Histamine釋放的stimuli：血管活性胺:

Histamine組胺andSerotoninphysicalinjurybindingofAbtomastcells(allergies)anaphylatoxins(C3aandC5a)細胞來源的炎癥介質(zhì)

花生四烯酸AA代謝產(chǎn)物eicosanoids前列腺素prostaglandins，PG白細胞三烯leukotriene，LT脂質(zhì)素lipoxins，LXAA主要存在于細胞磷脂膜中（糖皮質(zhì)激素抑制磷脂酶活性使AA不能解離）主要來源:白細胞/肥大細胞/內(nèi)皮細胞/血小板參與介導(dǎo)炎癥的每一步

AA代謝途徑CyclooxygenasesproducesPGPGI2,PGD2,PGE2mediatedvasodilationandincreasedvascularpermeabilityPGE2alsomediatesfeverandpain

前列腺素

LipoxygenasesproducesLTLTB4attractsandactivatesneutrophils趨化中性粒細胞LTC4,

LTD4,LTE4mediatevasoconstriction,bronchospasm,andincreasedpermeability

白三烯

PharmacologicInhibitorsofPG<CyclooxygenaseinhibitorsNonsteroidalanti--inflammatorydrugs(NSAIDs)…aspirin,ibuprofenSelectiveCOX-2inhibitors(increasetheriskofcardiovascularandcerebrovascularevents)Corticosteroids(reducethetranscriptionofgenesencodingCOX-2,phospholipaseA2,IL-1,TNFandiNOS)

非甾體類抗炎藥

糖皮質(zhì)激素

補體類介質(zhì)Positivevasculareffects(C3aandC5a)Leukocytechemotaxis(C5a)Opsonizationandphagocytosis(C3b)Celllysis(MAC,membraneattackcomplex)凝血系統(tǒng)和激肽系統(tǒng)

Coagulationproteins:uncertainHagemanfactorisimportantinDICKininsystem–cleavesHMWKtobradykininwhichmediatesvasodilation,increasedvascularpermeability,andpain

血漿中的炎癥介質(zhì)激肽系統(tǒng)補體系統(tǒng)凝血系統(tǒng)纖溶系統(tǒng)急性炎癥的病理學類型漿液性炎Serous…

纖維素性炎Fibrinous…

化膿性炎Suppurative(purulent)…

出血性炎

hemorrhagic漿液性炎

Askinblister口唇皰疹

皮膚水皰皮膚水皰Skinblisters

胸腔積液

pleuraleffusion纖維素性炎...絨毛心絨毛心“Breadandbutter”Pericarditis纖維素性炎...絨毛心Earlyorganizationofthefibrinousexudate粘連性心包炎adhesivepericarditis

限制性心包炎constrictivePericarditis

假膜性炎粘膜發(fā)生的纖維素性炎APSEUDOMEMBRANE(假膜)resultswhentheupperportionofamucosalsurfaceundergoesnecrosis,freeingfibrinogenfromvesselsthatthenclotsalongthesurface白喉Diphtheria白喉Diphtheria支氣管內(nèi)纖維素性滲出形成假膜…病人，女，87歲，腸鏡圖片（黑色箭頭：假膜；白色箭頭：腸粘膜紅腫）鏡下示假膜形成病史

病人（女，87歲）因右下肺肺炎在他院治療，10天前出院。出院后遵醫(yī)囑每日口服莫西沙星moxifloxacin，強力霉素doxycycline。出院后漸感虛弱，氣短。便秘，間中排數(shù)次稀便。

假膜性腸炎47yearoldpatientwhorecentlyfinishedacourseofantibiotics,nowhaswaterydiarrheaandabdominalpain.

ClostridiumdifficileinfectionRecenthistoryofantibioticuseSuddenleukocytosisAgeandfrailcondition①如何診斷?②如何治療?

急性大葉性肺炎

正常急性大葉性肺炎

Pulmonaryfibrosis(complication)化膿性炎滲出液

exudates中含大量中性粒細胞，壞死組織和水腫液，稱膿液

pus。壞死的中性粒細胞稱膿細胞。表面化膿…粘膜和漿膜表面積膿…積于體腔蜂窩織炎…彌散膿腫abscess…局限化膿性腦膜炎Purulentmeningitis

GyrusSulus化膿性腦膜炎化膿性腦膜炎化膿性闌尾炎化膿性闌尾炎

appendicitis正常闌尾化膿性闌尾炎闌尾腔闌尾腔中的膿液化膿性闌尾炎正常闌尾（示肌層）化膿性闌尾炎討論

Whentreatedpromptly,mostpatientswithpurulentappendicitisrecoverwithoutdifficulty.Iftreatmentisdelayed,theappendixcanburst,causingperitonealinfectionandevendeath.

要點：①蜂窩織炎

②闌尾壁結(jié)構(gòu)特點Why?咽喉蜂窩織炎咽喉蜂窩織炎膿腫

Abscess組織內(nèi)局限性化膿性炎癥化膿菌seeding壞死灶繼發(fā)感染形態(tài):中心壞死形成膿液（膿腔）周邊肉芽組織包裹（膿腫膜）疤痕修復(fù)小葉性肺炎/支氣管肺炎肺炎伴膿腫形成腎膿腫肝膿腫癤癤、癰癰Toothabscess臀部深部膿腫伴肛周瘺管形成Cavityduetopulmonaryabscessacutepyelonephritis急性炎癥的結(jié)局①③②

offendingagentstissuedestructionrepairclearedpersistentstopcontinue

SARSSARS

suvivingpatientDifusseinterstitialpulmonaryfibrosis慢性炎癥持續(xù)時間長(weekstoyears)可由急性炎癥發(fā)展而來，也可隱匿起病，病人沒有急性表現(xiàn)

炎癥，組織損傷和修復(fù)同時進行inflammation,tissueinjuryandattemptsatrepaircoexist慢性炎癥病因持續(xù)感染(mostcommon)Autoimmuneandallergicreactions

Prolongedexposuretopotentiallytoxicagents(silicosis,

Atherosclerosis)Alzheimerdisease,metabolicsyndrome,type2diabetes,andcertaincancers

mycobacteriaparasitesfungivirus慢性炎癥的病變特點單個核細胞浸潤Infiltration

withMφ,lymphocytes,andplasmacells組織損傷Tissuedestruction

byoffendingagentsorinflammatorycells瘢痕修復(fù)Attemptsathealing

angiogenesisandfibrosis

Chronic?inflammation?in?the?lungAwoundattheankleofaJapanesemanwhohasahistoryofcaninebite25yearsago.足分支菌病足分支菌病Mycetoma(madurafoot)

嚴重病例

慢性膽囊炎Normalgallbladder炎性息肉inflammator