炎癥醫(yī)學(xué)知識培訓(xùn)

ChapterIVInflammation第1頁SectionIIntroductoryRemark

I.

TheConceptofInflammationTheDefinitionandSignificanceofInflammation:

Inflammation炎癥Inflammationisthelocaldefensiveresponses局部防御反映toinjuryfactorsbylivingorganismspossessofvascularsystem擁有血管系統(tǒng).

第2頁

Atfirst,weshouldbringoutthegeneralideaoftheinflammation.1.

Itisformingstepbysteptofightagainstinjuryduringthecourseofevolutionoforganism.生物進(jìn)化中產(chǎn)生●UnicellularorganismNon-vascularsystemPinocytosismulticellularorganism(e.g.parasite,invertebrate無脊椎動物)●TheorganismpossessofvascularsystemVasoresponseiscardinalfeatureofdefenseresponseContainofpinocytosis第3頁2

.

Vasculareventsplaythecentralroleofinflammatoryresponse血管反映為中心3.Itisamorestereotypednonspecificbiologicaldefensivemechanismagainstanyoftheenvironmentalinvaders反映是定型旳.4.Thesearethe3majorpathologicalchangeofinflammation,namely,Alteration,Exudation,&Proliferation變質(zhì)、滲出、增生5.Itisnot,initself,adisease,butisusuallyamanifestationofdisease,andusuallyaccompaniedwithfeverandleukocytosis是臨床體現(xiàn)，如發(fā)熱、白細(xì)胞增多第4頁6.Instudyingtheprocessofinflammation,weshouldn’tignoreeitherofthese2sidefortheyareunifiedinonecoin.有益有害兩方面Ontheonehand:Inflammationmayhavebeneficialeffects,suchasthedestructionofinvadingmicro-organismsandwalling-offofanabscesscavity,thuspreventingspreadofinfection.Ontheotherhand:Inflammationmayalsohaveharmfuleffects,forexample:第5頁Anabscessinthebrainwouldactasaspace-occupyinglesioncompressingvitalsurroundingstructures.

Fibrosisresultingfromchronicinflammationmaydistortthetissueandpermanentlyaltertheirfunction(e.g.livercirrhosis).Inchildrentheswellingoftheepiglottisinacuteepiglottitismayobstructtheairway.

第6頁

II.Thecausesofinflammation炎癥因素●Causesofcellulardamagearestillcausesofinflammation.●Theprincipalcausesofinflammationincludedbiologicalagents,physicalagents,chemicalagents,immunologicalreactionsandgeneticagents

etc.●Thebiologicalagentsaremostimportantandcommoncausesofinflammation.(e.g.bacteria,virus,rickettside,fungi,andparasiteetc.)●‘Infection’感染Itisakindofinflammationduetobiologicalpathogen.第7頁physicalagents,涉及高溫、低溫、外傷、放射線chemicalagents,強(qiáng)酸、強(qiáng)鹼，某些毒性化學(xué)物質(zhì)以及體內(nèi)產(chǎn)生旳化學(xué)物質(zhì)（如壞死組織旳崩解產(chǎn)物，膽囊穿孔，膽汁流入腹腔、消化液旳外溢等）。immunologicalreactions如各型變態(tài)反映geneticagents如α１抗胰蛋白酶缺陷第8頁

III.Theessentialchangeofinflammation

degenerationAlterationnecrosisfluidexudeExudationleukocyteexudemonocyte-macrophageProliferationendotheliocyte,fibroblastparenchyma(e.g.coverepithelium,glandularepithelium)第9頁IV.TheManifestation,SystemicResponse

ofInflammation

(I).Localappearance●Redness紅Anacutelyinflamedtissueappearsredforexampleskinaffectedbysunburn.Thisisduetodilatationofsmall

bloodvesselswithinthedamagedarea.●Swelling腫Swellingresultfromedema.●Heat熱Increaseintemperatureisseenonlyinperipheralpartsofthebody,suchastheskin.Itisduetoincreasedbloodflow(hyperaemia)throughtheregion.

第10頁

●Pain痛Itresultspartlyfromthestretchinganddistortionoftissueduetoinflammatoryedemaand,inparticular,frompusunderpressureinanabscesscavity.Someofthechemicalmediatorsofacuteinflammation,suchasprostaglandins前列腺素,areknowntoinducepain.●Lossoffunction功能障礙Movementofaninflamedareaisconsciouslyandreflexlyinhibitedbypain,whilesevereswellingmayphysicallyimmobilisethetissue.

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(II)Systemicresponse

●FeverSystemicfever,whichresultsfrom:Exogenouspyrogen:e.g.bacterialtoxins,somekindofvirus,IC,etc.Endogenouspyrogen:e.g.cellularfactor(IL-1,TNF)Prostagladin(PG)

第12頁●Leukocytosis──Forthepatient,itisoneoftheknownfeaturesofacuteinflammtion.Normal:4-10╳109/L類白細(xì)胞反映‘shifttotheleft’核左移:indicativeofsevereinfection

第13頁

Thekindofleukocyteofperipheralblood外周血isinrelationtoinfectivepathogen.●Acutesuppurativeinflammationandearlystagesofacuteinflammationincreaseofneutrophilicgranulocyte●Latestagesofacuteinflammationincreaseofmonocyte-macrophage

●

Chronicinflammationandvirusinfection

increaseoflymphocyteandmonocyte●Theinfectionofparasiteandallergosesincreaseofeosinophilicleukocyte

第14頁

resistanceislow,Leukopeniaindicativeofsevereinfectionsomekindofinfection

(e.g.typhoidfever傷寒,virusinfection)

第15頁

Theclinicaltypesofinflammation

炎癥旳臨床類型Theclinicaltypesofinflammationareclassifiedaccordingtocourseofdiseaseas:1.

Peracuteinflammation:thecoursepersistenceofsomehoursorafewdays.

Itisallergosescommonly.e.g.anaphylaxis過敏duetopenicillin;acutetransplantrejection第16頁2.

Acuteinflammation:thecoursepersistenceofseveraldays,don’texceedamonthcommonly.thepathologicalchangesaremajorofalteration變質(zhì)andexudation滲出,andincreaseofneutrophilicgranulocyte中性白細(xì)胞.3.Chronicinflammation:thecoursemaybeprolongedforseveralmonthsorseveralyears.thepathologicalchangearemajorofproliferation增生,andincreaseoflymphocyte,plasmocyteandmonocyte淋巴細(xì)胞、漿細(xì)胞、單核細(xì)胞.4.Subacuteinflammation:Itisintermediatebetweenthatofacuteinflammationandthatofchronicinflammation.e.g.subacutesevereheptitissubacuteinfectiveendocarditis

第17頁

SectionIIAcuteInflammation

Acute

inflammationisanimmediateanddirectdefensiveresponsetoinjuryfactorsbylivingorganismsinitsearlystage.

Vascularresponseplayingthecentralroleofchangesaremajorofexudation.Itincludefluid(antibody)andleukocyte(neutrophilicgranulocyte)病程短、起病急病變以變質(zhì)和滲出為主炎癥細(xì)胞以中性白細(xì)胞為主第18頁Exudation

Exudation滲出Edemafluid,fibrinandneutrophilpolymorphsaccumulateintheextracellularspacesofthedamagedtissue.Exudationofedemafluidandleukocyteisknownas‘exudate滲出物’.Exudate,especiallyneutrophilpolymorph,isessentialforahistologicaldiagnosisofacuteinflammation.Majorcoursesofexudationarechangesinhemodynamics,increasedvascularpermeability血管通透性,fluidexudateandcellularexudate.

第19頁I.Changesinhemodynamics1.

Microarteriospasm痙攣:transientvasoconstriction(thecoursespersistenceofafewsecond)

2.

Vasodilatationandaccelerationofbloodflow:(inflammatoryhyperemia)

3.Bloodflowbeginstoslow

4.(atleast,occurstasis)

第20頁II.Increasedvascularpermeability

1.Constrictionofendothelialcell2.

Transcytosis3.

Endothelialinjury4.

Highpermeabilityofnewlyformedcapillarywall第21頁FluidexudateExudationoffluidrichproteiniscalledexudate滲出液.Inflammatoryedema炎性水腫：exudateaccumulateintheextracellularspace.Inflammatoryhydrops積液：exudateaccumulateintheserosalcavity.

第22頁水腫發(fā)生簡要機(jī)制：體內(nèi)外液體互換失衡：球－管失衡血管內(nèi)外液體互換失衡①毛細(xì)血管流體靜壓②血漿膠體滲入壓③血管通透性④淋巴回流第23頁Table4-1comparisonofexudateandtransudate

transudate

exudate

vasopermeabilitynomal

increase

Containofprotein

0-1.5g/dl

0-1.5g/dl

Kindsofprotein

Majorofalbumin

Variousofprotein

Rivaltatext

negative

positive

fibrin

without

possess

Specificgravity

<1.012

>1.020

Thenumberofcells

<0.1╳109/L

>0.5╳109/L

第24頁●Beneficialeffectsofexudate:a.Dilutionoftoxins稀釋毒素,suchasproducedbybacteria,allowsthemtobecarriedawayinlymphatics.b.

Neutralizationoftoxins中和毒素entryofantibodies,theymayleadeithertolysisof

micro-organisms,

throughtheparticipationofcomplement,ortotheirphagocytosisbyopsonization.C.Fibrinformation纖維素itfromexudedfibrinogenmayimpedethemovementofmicroorganisms,trappingthemandsofacilitatingphagocytosis吞噬作用.

第25頁‘Surfacephagocytosis’表面吞噬作用

Itisthoughtthatphagocytosismaybefacilitatedifthebacteriumcanbetrappedorcorneredagainstasurface,suchasstrandsoffibrin,orintheintersticesbetweentwoormorecells.第26頁

●

Harmfuleffectsofexudate:Edemaoftissuesmayincreaseinseverityoflocaldisturbanceofcirculation.

Severeswellingoftheepiglottisinacuteepiglottitismayobstructtheairway.Excessivehydropsmayhaveabedeffectonorganfunction.(e.g.hydropericardium心包積水,hydrothorax胸腔積水)Organizationoffibrinmayleadtopulmonarycarnification肺肉質(zhì)變andadhesion粘連(e.g.adhesiveperitonitis腹膜炎,adhesivepericarditis心包炎,adhesivepleurisy胸膜炎).

第27頁III.Cellularexudateanditseffects

Inflammatorycellinfiltration炎癥細(xì)胞浸潤:Theaccumulationofleukocyteswithintheextravascularspace.Itisthemostimportantaspectoftheinflammatoryprocess.第28頁LeukocytestransmigrationItincludemajorofthreestepsby:

1.Marginationandpavementingofleukocytes2.Adhesion3.Transmigration

第29頁‘Redcelldiapedesis’紅細(xì)胞漏出

Itisnegativeprocessofredcelldiapedesis.Thesighofredcelloccuredinextravascularspacesaresuggestiveofsevereinjury.第30頁

3.Leukocytestransmigration

ofinjuredareaandchemotaxisChemotaxis趨化作用

UnidirectionalmigrationofWBCtothesiteofinjuryismediatedbydiffusiblechemicalattractantsThischemicalattractantiscalledchemotacticagents趨化因子.第31頁2mainsourcesofchemotacticagents:

Exogenousbacterialproducts

Endogenousderivedfromplasmaproteins(complements,C5a)orleukotreneB4andchemokine(IL-8,MCP,lymphotactin巨噬細(xì)胞、淋巴細(xì)胞趨化蛋白).

第32頁4.Theeffectsofleukocytes(1).Phagocytosis吞噬殺滅作用Phagocytosisbyleukocytesinvolvesrecognition辨認(rèn),engulfment吞入,

killing殺滅,and

degradation消化ofngestedmaterial.Leukocytepossessionofphagocytosismaybecalledphagocyte.

第33頁1).kinds,structuresandfunctionofphagocytesi.neutrophils(microphages)Around60%ofthetotalnumberofperipheralleukocytesLM:laboidnucleus,Neitrophilicgranules(azurophilicgranules,specificgranules)EM:lysosoma

第34頁ii.MacrophageMonocyteMacrophageHistocyte

(Kupffer’scell,sinusoidhistocyte,dustcell,andmicrogliocyte,etc.)

第35頁iii.EosinophilicleukocyteItisalittlelargerthanneutrophilrodnucleusorlaboidnucleus,eosinophilicgranulesItsphagocytosisisweakandphagocytosisofIC.第36頁Kindsandstructuresofphagocytes第37頁Thekindsofleukocytesofinfiltrationareinrelationtostagesofinflammation.●Theearlystagesofmajorofacuteinflammationincreaseofneutrophilicgranulocyte(6-24h)●Latestagesofacuteinflammationincreaseofmonocyte-macrophage(24-48h)

第38頁Thekindsofleukocytesofperipheralbloodarealsoinrelationtoinfectiveinflammatoryfactors.●Acutesuppurativeinflammation急性化膿性炎、一般細(xì)菌感染increaseofneutrophilicgranulocyte特殊細(xì)菌感染。如結(jié)核，

increaseofmonocyte●

Virusinfection

病毒感染increaseoflymphocyteandmonocyte●Theinfectionofparasiteandallergoses寄生蟲和變態(tài)反映increaseofeosinophilicleukocyte第39頁2).Phagocyticcoursei.Recognitionandattachment(opsonization)(thereceotorofFcandC3b)調(diào)理素，調(diào)理素化作用ii.Engulfment,formingphagosome,furtherformingphagolysosome(degranulation)iii.killingordegradation

第40頁Thereare2majorcategoriesofbactericidalmechanisms:a).Oxygen-dependentmechanismsleukocyticoxidaseisactivated(NADPHoxidase還原型輔酶)→H2O2→(MPO髓過氧化物酶)→HOCl.次氯酸b).Oxygen-independentmechanismsLysosomalenzymes溶酶體酶;lysozyme;arginine-richcationicproteins(phagocytins)Bactericidalpermeabilityincreasingprotein,BPI

細(xì)菌通透性增高蛋白第41頁(2).Immuneeffects免疫作用MacrophagesphagocytoseantigenandsendmessageofantigentoT-cellsandB-cellsT-cellsreleasethelymphokine(cellularimmunity)B-cellsproducetheimmunoglobulin(humoralimmunity)NK-cell(naturalkillercell)分泌作用：白細(xì)胞介素、干擾素、腫瘤壞死因子(3).Effectsoftissueinjury

組織損傷（悲觀作用，副反映）第42頁IV.InflammatoryMediator

Inflammatorymediator炎癥介質(zhì)

Alotofacuteinflammatoryresponseduetoendogenouschemicalmediators.Thesechemicals,calledinflammatorymediator.

第43頁Thegeneralfeatureofinflammatorymediator1.Inflammatorymediatorsarefromcellsandplasma.Theformerisstoredinthecellbygranulesinform;Thelatterispresentinplasmabyprecursorinform.

細(xì)胞以顆粒形式釋放，血漿中此前體激活形式激活2.Therelationofinflammatorymediatorandtargetcell(i.specific特異性;ii.secondaryresponse二級反映;iii.Nonspecific非特異性)3.Alotofinflammatorymediatorsarepossessedofpotentialdangeroftissue有潛在旳危害.

第44頁Majorofinflammatorymediatoranditseffects

(I)Inflammatorymediatorsarereleasedfromcells1.Vascularamines血管活性胺:includeofhistamine組織胺and5-hydrooxytryptamine5-羥色胺

第45頁1).Histamine:Itisstoredinmastcells主細(xì)胞,basophil嗜堿性白細(xì)胞andplatelets血小板.Histaminereleasefromthesesites(forexample,mastcelldegranulation)isstimulatedbycomplementcomponents補(bǔ)體C3aandC5a,andbylysosomalproteins溶酶體酶releasedfromneutrophils.Itcausesvasculardilatationandimmediatetransientphaseofincreasedvascularpermeability血管擴(kuò)張，通透性增高.

第46頁2).5-hydrooxytryptamine,5-HT:

5-羥色胺Thisispresentinhighconcertrationinmastcellsandplateles.Italsoincreasevascularpermeability.

第47頁2.Metaboliteofarachidonicacid,AAphospholipasephospholipidofmembraneAA

Itincludeprostagladin前列腺素(PG),leukotrene白細(xì)胞三烯(LT),andlipoxins脂毒素.

前列腺素：

合成：組織損傷→溶酶體酶中旳磷脂酶釋放→細(xì)胞膜磷脂→20碳脂肪酸→前列腺素合成酶→前列腺素

第48頁P(yáng)rostagladin,PGTheseareagroupoflong-chainfattyacidsderivedfromarachidonicacidandsynthesisedbymanycelltypes.Itcausesvasculardilatation血管擴(kuò)張and

increasesinvascularpermeability通透性增高

Itmaycausesfever發(fā)熱andpain疼痛.

第49頁3.productofleukocyteandlysosomalcompoundsactiviticproductsofoxygenmetabolism(O2.-,H2O2,OH.)

lysosomalcompounds溶酶體成分

第50頁4.Cytokineandchemokine細(xì)胞因子和趨化性細(xì)胞因子Theformer,afamilyofchemicalmessengersreleasedbylymphocytesandmonocytes.(lymphokine,monokine).TheletterincludeIL-8,MCPandlymphotactin.

第51頁(II)

Plasmafactors:

Plasmafactorsincludecomplementsystem,kininsystemandclottingsystem.三個系統(tǒng)：補(bǔ)體系統(tǒng):C3a、C5a趨化因子、C3b調(diào)理素激肽系統(tǒng)：如緩激肽凝血系統(tǒng)：纖維素滲出，限制細(xì)菌播散、利于中性白細(xì)胞捕獲細(xì)菌

第52頁Kininsystem:Bradykinin緩激肽isthemostimportantvascularpermeabilityfactorBradykininisalsoachemicalmediatorofthepainwhichiscardinalfeatureofacuteinflammation.

ThekininsystemisactivatedbycoagulationfactorXIIProductsofthekinin,coagulationandfibrinolyticsystemcanactivatecomplement.

第53頁V.CommonHistologicPatternsof

AcuteInflammation

Alterativeinflammation變質(zhì)性炎Majorpathologicalchangesarealteratione.g.a.acuteseverehepatitis;b.amoebiasisc.encephalitisd.myocarditis(duetodiphtheriatoxin白喉毒素)

第54頁

Proliferativeinflammation增生性炎Inearlystagesofacute

inflammation,

hemajor

pathologicalchangeare

proliferatingrightaway.e.g.

a.typhoidfeverb.acutediffuse

proliferativeglomerulonephritisc.forminggranuloma肉芽腫phase

ofrheumatism第55頁Exudativeinflammation滲出性炎(I)

SerousinflammationInserousinflammation,thereisabundantprotein-richfluidexudatewitharelativelylowcellularcontent.Mildinjurytothevascularendothelium漿液滲出為主，預(yù)后好。

第56頁Thesiteofpredilection:a.areolartissue疏松結(jié)締組織

(e.g.bebitbythanatophidia)b.serouscavities漿膜腔

(e.g.pleuritis,peritonitis胸膜炎、腹膜炎)c.mucus粘膜

(e.g.earlystageofcommoncold)Catarrhalinflammation卡他性炎:

When

mucus

hypersecretionaccompaniesacute

inflammation

ofamucousmembrane,the

appearanceisdescribedas

catarrhald.synovialmembrane滑膜

(e.g.acutesynovitis)e.skin皮膚

(e.g.II゜burn,frictioninjuryofskin)

第57頁(II)

FibrinousinflammationWhentheinflammatoryexudatecontainsplentifulfibrinogen,thispolymerisesintoathickfibrincoating.Withmoresevereinjuries,theresultinggreatervascularleaksarelargeenoughtopermitthepassageoffibrinogenmolecules.Thesiteofpredilection:a.mucosalfibrinousinflammationpseudomembranousinflammation假膜性炎:e.g.diphtheria白喉bacillarydysentery菌痢b.serosalfibrinousinflammatione.g.pleuritis,peritonitisrheumaticpericarditis(corhirsutum絨毛心)

c.fibrinousinflammationoflung

e.g.lobarpneumonia

大葉性肺炎第58頁

diphtheria

rheumaticpericarditis

(corhirsutum)第59頁(III)suppurativeorpurulentinflammationItisitsfeaturethatmajorof

neutrophilsexudate中性白細(xì)胞滲出

accompaniedwithvaryingdegreeson

necrosisoftissue不同限度液化壞死

andformingpus形成膿液.Pusconsistsoflargeamountsofdyinganddegenerationneutrophils,infectingorganisms,liquefyingnecrosisoftissueandsmallamountsofserum.

第60頁1.PurulentinflammationofsurfaceandempyemaPurulentinflammationofsurface表面化膿P(yáng)urulentinflammationoccursonmucusorserousItisalsocalled‘purulentcatarrh’.Empyema積膿ahollowviscusfillswithpuse.g.empyemaofthegallbladderoroftheappendix

第61頁2.Phlegmonousinflammation蜂窩織性炎

Diffuse彌漫formpurulentinflammationoccurstoareolartissue疏松組織.3.Abscess膿腫

Abscessisakindoflocalized局限purulentinflammationItsmajorfeaturesareliquefyingnecrosisoflocaltissueandformationofacavity膿腔filledpus.

第62頁急性闌尾炎總菜單第63頁Abscessofkidney

第64頁Table4-1comparisonofphlegmonousinflammationandabscess

Phlegmonousinflammation

Abscess

Commonsite

Hypodermis,muscle,appendix

Skin,organ

Pathogenicbacteria

Hemolyticstreptococcus

Goldenstaphylococcus

Therangeoflesion

Diffuseandspreading

Welllocolized

ThedegreeofnecrosisMild

Severe

第65頁‘metastaticabscess’‘chronicabscess’‘furuncle’癤‘carbuncle’癰‘ulcer’潰瘍‘sinus’竇道‘fistula’瘺管第66頁(IV)Hemorrhagicinflammation出血性炎Muchmoresevereorveryintenseinjurieswouldcausethevascularleakareevenlarge,renderingnotonlythepassageofthelargestplasmaproteinmoleculesbuttheRBC,suchasincertainintenseinfectiousdiseasee.g.plague鼠疫,anthrax炭疽,leptospirosis鉤端螺旋體病,andepidemichemorrhagicfever流行性出血熱etc.

第67頁VISequelaeofAcuteInflammation

(I)

ResolutionandHealing(II)ToDelayRecoverResistanceisloworthorough

treatmentcannotbemadeSomekindsofacuteinflammationmaytransformationintochronicinflammation.

(e.g.chronicappendicitis)Somekindsofchronicinflammationaredelayrecovery.(e.g.chronicbronchitis,chronichepatitis)

(III)ToSpread第68頁(III)ToSpread1.Localspreade.g.abscess→sinus,fistulanephrotuberculosis腎結(jié)核

→ureter,bladderTB2.Lymphaticspreade.g.primarycomplex原發(fā)綜合征3.Vascularspread

第69頁3.Vascularspread(1)bacteremia菌血癥bacteriaenterblood,notoxin(2)toxemia毒血癥toxinabsorbinblood,nobacteria(3)septicemia敗血癥

bacteremia+toxemia(4)pyemia膿毒血癥thespecificsepticemiaduetopyococcusformingofmultiplemicroabscess(embolicabscess)

第70頁SectionIIIChronicInflammation

TheCausesandClassificationofChronic

Inflammation病程長，起病緩；增生為主；淋巴細(xì)胞、漿細(xì)胞浸潤Itmightstartasanacuteonewhichistransformedintochronic,or,itmaybechronicfromtheonset.Inthelatterinstance,itdependsmainlyonthenatureoftheinflammatorystimulus.3majoraspectcanbeindicated:

i.

Persistentlowvirulent毒力低旳細(xì)菌感染infections,

suchas

chronicgastritisduetoHPinfectionand

tuberculosisduetotuberclebacillus.

ii.

Prolongedexposuretonon-degradablematerial,

suchassilica硅,etc.

iii.Autoimmunediseases自身免疫疾病andallograft

rejection變態(tài)反映第71頁Accordingtothefeatureofchronicinflammation,itmaybeclassified2typesasnonspecificandspecificchronicinflammation(granulomatousinflammation肉芽腫性炎).

第72頁TheTypesof