血液专业知识培训培训课件1

血液血液专业知知识培培训BodyFluid=60%ofBodyWeight(BW)IntracellularFluid2/3,40%ofBWExtracellularFluid1/3,20%ofBWPlasma5%ofBWInterstitialFluid15%ofBW70kgMale,42LInternalenvironment（内环境）2血液专业知识培训ExtracellularFluid1/3,20%ofBWPlasma5%ofBWInterstitialFluid15%ofBWInternalEnvironment3血液专业知识培训4血液专业知识培训Homeostasis（稳态）Homeostasis(from the Greek words for“same”and“steady”):maintenanceofstaticorconstantconditionsintheinternalenvironmentWalterB.Cannonhttp:/www.harvardsquarelibrary.org/unitarians/cannon_walter.html5血液专业知识培训ComponentsofHomeostasis:lConcentrationofO2andCO2lpHoftheinternalenvironmentlConcentrationofnutrientsandwasteproductslConcentrationofsaltandotherelectrolyteslVolumeandpressureofextracellularfluid6血液专业知识培训-RegulationBodyssystemsoperatetogethertomaintainhomeostasis:SkinsystemSkeletalandmuscularsystemCirculatorysystem RespiratorysystemDigestivesystemUrinarysystemNervoussystemEndocrinesystemLymphaticsystemReproductivesystemHowishomeostasisachieved?7血液专业知识培训ComponentsofbloodPlasma（血浆）BloodCellsRedBloodCells(RBC)orErythrocytes（红细胞）WhiteBloodCells(WBC)orLeucocytes（白细胞）Platelets(PLT)orThrombocytes（血小板）8血液专业知识培训9血液专业知识培训10血液专业知识培训11血液专业知识培训12血液专业知识培训13血液专业知识培训Plasmaincludeswater,ions,proteins,nutrients,hormones,wastes,etc.Thehematocrit（血细胞比容）isarapidassessmentofbloodcomposition.ItisthepercentofthebloodvolumethatiscomposedofRBCs(redbloodcells).14血液专业知识培训thevolumeofredbloodcellsasapercentageofcentrifugedwholebloodM:4050%F:3748%Hematocrit（packedcellvolume,血细胞比容）血细胞比容）InternationalCouncilforStandardizationinHaematology(ICSH)RecommendationsforSurrogateReferenceMethodforthePackedCellVolume15血液专业知识培训Physical&chemicalpropertiesofblood1.SpecificGravity（比重）Dependingonhematocrit&proteincompositionWholeblood：1.0501.060Plasma：1.0251.035Redbloodcells：1.09016血液专业知识培训2.Viscosity（粘度）relativeviscosityofwholeblood45dependingonhematocritrelativeviscosityofplasma1.62.4relatedtotheproteincompositionoftheplasma17血液专业知识培训3.OsmoticPressure（渗透压）Theosmoticpressureofasolutiondependsonthenumberofsoluteparticlesinthesolution,NOTontheirchemicalcompositionandsize18血液专业知识培训Plasmaosmoticpressure(300mOsm/L）CrystalloidOsmoticPressure（晶体渗透压）Pressuregeneratedbyallcrystalsubstances,particularlyelectrolytesImportantinmaintainingfluidbalanceacrosscellmembranesColloidOsmoticPressure（胶体渗透压）Osmoticpressuregeneratedbyplasmaproteins,particularlyalbumin.Approximately25mmHg,butimportantinfluidtransferacrosscapillaries19血液专业知识培训4.PlasmapHNormalrange:7.357.45Buffersystems（缓冲系统）:NaHCO3/H2CO3,Pro-Na/Pro,Na2HPO4/NaH2PO4Hb-K/Hb,HbO2-K/HbO2,K2HPO4/KH2PO4,KHCO3/H2CO320血液专业知识培训FunctionsofbloodTransportationO2andCO2Nutrients(glucose,lipids,aminoacids)Wasteproducts(e.g.,metabolites)HormonesRegulationpHBodytemperatureProtectionBloodcoagulationImmunity21血液专业知识培训BodyFluid=60%ofBodyWeight(BW)IntracellularFluid2/3,40%ofBWExtracellularFluid1/3,20%ofBWPlasma5%ofBWInterstitialFluid15%ofBW70kgMale,42LPlasma22血液专业知识培训Water(92%ofplasma)servesastransportmedium;carriesheatProteins(68%ofplasma)Inorganicconstituents(1%ofplasma)e.g.,Na+,Cl-,K+,Ca2+Nutrientsglucose,aminoacids,lipids&vitaminsWasteproductse.g.,nitrogenouswasteslikeureaDissolvedgasesO2&CO2HormonesuComposition23血液专业知识培训Plasmaproteins24血液专业知识培训Albumins（白蛋白）(60-80%ofplasmaproteins)mostimportantinmaintenanceofosmoticbalanceproducedbyliverGlobulins（球蛋白）(1-,2-,-,-)importantfortransportofmaterialsthroughtheblood(e.g.,thyroidhormone&iron)clottingfactorsproducedbyliverexcept-globulinswhichareimmunoglobulins(antibodies)producedbylymphocytesFibrinogen（纤维蛋白原）importantinclottingproducedbyliver25血液专业知识培训Red blood cells(Erythrocytes)（红细胞）26血液专业知识培训StructureBiconcaveNonucleusFeworganellesSmallHemoglobinmolecules27血液专业知识培训uCountRBCcountM:4.05.51012/LF:3.55.01012/LHemoglobin（血红蛋白）M:120160g/LF:110150g/L28血液专业知识培训uPhysiologicalpropertiesPlasticdeformability（可塑变形性）29血液专业知识培训ErythrocyteSedimentationRate(ESR)（红细胞沉降率）ThedistancethatredbloodcellssettleinatubeofbloodinonehourNormalvalueWestergrenmethod（魏氏法，国际血液学标准化委员会推荐魏氏法为标准法）:M:015mm/h，F:020mm/hAnindicationofinflammationwhichincreasesinmanydiseases,suchastuberculosis&rheumatoidarthritisdSuspensionstability（悬浮稳定性）InternationalCouncilforStandardizationinHaematology(ICSH)30血液专业知识培训红细胞叠连（rouleauxformation）31血液专业知识培训Osmoticfragility（渗透脆性）thesusceptibilityofaredbloodcelltobreakapartwhenexposedtosalinesolutionsofalowerosmoticpressurethanthatofthehumancellularfluid32血液专业知识培训Notice that hemolysis begins in the 0.45%tube and is complete in the 0.35%tube.33血液专业知识培训Onlysubstanceswhichactasimpermeantmoleculescanbeusedtomakeisotonicsolutions（等张溶液）.E.g.cellsplacedinanisosmoticsolution（等渗溶液）ofurea(1.9%),apermeantmolecule,willswellandbust.SolutionswhichhavethesamecalculatedosmoticpressurearesaidtobeISOSMOTICbutarenotnecessarilyISOTONIC34血液专业知识培训uFunctionofRBCs 1.TransportofO2andCO22.Buffering35血液专业知识培训uProductionofRBC(Erythropoiesis)36血液专业知识培训HemocytoblaststemcellStemcellbecomescommittedEarlyerythroblastshaveribosomesErythroblastsaccumulateironandhemoglobinNormoblastsejectorganellesReleasedaserythrocyte37血液专业知识培训NutritionalRequirementsforErythropoiesis1.Manyvitamins,minerals,andproteinsarenecessaryfornormalRBCproduction2.Clinically,folicacid（叶酸）,VitB12,andiron（铁）arethemostimportant.Deficienciesofthesefactorsleadtocharacteristicanemias（贫血）38血液专业知识培训39血液专业知识培训Diagramofironkineticsfromironstorestodevelopingredbloodcell(RBC).Ironstoresincludethebonemarrow,reticuloendothelialsystem(liverandspleen)andRBCs.Transferrin(totaliron-bindingcapacityTIBC)transportsiron(Fe)todevelopingerythrocytes.IronisdepositedintheRBC,andtransferrinreturnstostoragesitestobindmoreFefortransport.Lactoferrinisacompetitoroftransferrin;ittakesFethatisfreeandreturnsittostoragesites.Lactoferrinlevelsareelevatedinanemiaofchronicdisease.Increasesininterleukin-1increasethesequestrationofFeinstoragesites.(Hb=hemoglobin)40血液专业知识培训uRegulationofErythropoiesis1.Erythropoietin（促红细胞生成素）2.Hormones:Androgen（雄激素）OthersHypoxia-induciblefactor-1,HIF-141血液专业知识培训Erythropoiesisishormonallyregulated:decreasedoxygendeliverytothekidneycausesthesecretionoferythropoietin,whichactivatesreceptorsinbonemarrow,leadingtoanincreaseintherateoferythropoiesis.42血液专业知识培训averagelifespan=about120daysuDestructionofRBCMacrophagesengulfoldRBCsIronissalvagedHemedegradesintobilirubin43血液专业知识培训Anemia（贫血）Anemiaisdefinedasaqualitativeorquantitativedeficiencyofhemoglobin,aproteinfoundinsideredbloodcells(RBCs)Thethreemainclassesofanemia：excessivebloodloss(acutelysuchasahemorrhageorchronicallythroughlow-volumeloss)excessivebloodcelldestruction(hemolysis)deficientredbloodcellproduction(ineffectivehematopoiesis)44血液专业知识培训Irondeficiencyanemia（缺铁性贫血）（缺铁性贫血）45血液专业知识培训巨幼红细胞性贫血（megaloblasticanemia）46血液专业知识培训47血液专业知识培训Hemolysis（溶血）（溶血）Redbloodcellswithout(leftandmiddle)andwith(right)hemolysis.Notethatthehemolyzedsampleistransparent,becausetherearenocellstoscatterlight.48血液专业知识培训Whitebloodcells(Leucocytes)（白细胞）（白细胞）uTypesofWBC 49血液专业知识培训WBCCount(109/L)%GranulocytesNeutrophils2.07.05070Eosinophils0.020.50.55Basophils00.101Monocytes0.120.838Lymphocytes0.84.02040Total410uWBCcount 50血液专业知识培训LeukopoiesisMyeloblastsbecomeallofthegranularleukocytesMonoblastsbecomemonocytesLymphoblastsbecomelymphocytes51血液专业知识培训52血液专业知识培训Platelets(Thrombocytes)uFormedinthebonemarrowfromcellscalledmegakaryocytesuWithoutnucleus,butcansecreteavarietyofsubstancesunormalvalue:(100300)x109/LuAveragelifespan=714daysuPlayanimportantroleinhemostasis53血液专业知识培训1.AdhesionPlateletsadheretothevesselwallatthesiteofinjuryuPhysiologicalpropertiesofplatelets vonWillebrandfactor,vWF54血液专业知识培训55血液专业知识培训Unifyingmodelofplateletadhesiontocollagenatarterialshear.Twodifferentpathwaysbywhichhumanandmouseplateletsfirmlyadheretocollagenatarterialshearareillustrated.Inboth,themajorityofplateletsareinitiallytetheredtocollagenviaGPIb/IX/Vinteractingwithcollagen-boundVWF(left),althoughaminorityofplateletsinteractdirectlywithcollagenindependentlyofVWF/GPIb/IX/V.Inthefirstpathway(upper),signalingfromGPVIfirstleadstoactivationofintegrins21(GPIa/IIa)andIIb3(GPIIb/IIIa).Activatedintegrinsthenfirmlyattachtheplatelettocollagen,eitherdirectly(21)orviacollagen-boundVWF(IIb3)(right).Inthesecondpathway(lower),plateletsfirstadheretocollagenviaintegrin21,beforeGPVIengagescollagenandinducesactivation.Thesetwopathwaysarelikelytoreinforceeachotherandtheeventsofthrombusformation.Releaseofsecondarymediators(ADPandTxA2)wouldfurtherpotentiatetheseevents(right).(Redrawn from Auger JM,Kuijpers MJ,Senis YA:Adhesion of human and mouse platelets to collagen under shear:a unifying model.FASEB J 2005;19:825-827.)56血液专业知识培训2.AggregationPlateletsadheretooneanother57血液专业知识培训58血液专业知识培训PlateletAggregationPathwayPlateletactivationandcoagulationnormallydonotoccurwithinanintactbloodvessel.Aftervesselwallinjury,platelet-plugformationisinitiatedbytheadherenceofplateletstosubendothelialcollagen.Inhighsheararterialblood,plateletsarefirstsloweddownfromtheirbloodflowvelocitybyinteractingwiththecollagen-boundvonWillebrandfactor(VWF)andsubsequentlystoppedbybindingdirectlytocollagenviatheirglycoproteinreceptorcomplex.TheactivationofthesecollagenreceptorsonplateletsfollowingtheirbindingtocollagenactivatesphospholipaseC(PLC)-mediatedcascades.Thisresultsinamobilizationofcalciumfromthedensetubulasystem.Anincreaseinintracellularcalciumisassociatedwithactivationofseveralkinasesnecessaryformorphologicalchange,thepresentationoftheprocoagulantsurface,thesecretionofplateletgranularcontent,theactivationofglycoproteins,andtheactivationofPhospholipaseA2(PLA2).ActivationofPLA2releasesarachidonicacid(AA),whichisaprecursorforTBXA2synthesis.PTGS1catalyzesthefirststepintheformationofTBXA2fromAA.Thisreactionisirreversiblyblockedbyaspirin,whichalsoleadstotheblockageofplateletaggregationTheseprocessesresultinthelocalaccumulationofmoleculeslikethrombin,TBXA2,andADP,whichareimportantforthefurtherrecruitmentofplateletsaswellastheamplificationofactivationsignalsasdescribedabove.ThesecretedagonistsactivatetheirrespectiveGproteincoupledreceptors:thrombinreceptor(F2R),thomboxaneA2receptor(TBXA2R),andADPreceptors(P2RY1andP2RY12).TheP2RY12receptorcouplestoGi,andwhenactivatedbyADP,inhibitsadenylatecyclase.ThisinteractioncounteractsthestimulationofcAMPformationbyendothelial-derivedprostaglandins,whichalleviatestheinhibitoryeffectofcAMPonIP3-mediatedcalciumrelease.Thienopyridines,aclassoforalantiplateletagents,permanentlyinhibitP2RY12signaling,whichissufficienttoblockplateletactivation.F2R,TBXA2RandP2RY1coupletotheGq-PLC-IP3-Ca2+pathway,inducingshapechangeandplateletaggregation.Inaddition,receptorsignalingthroughG12/13(F2R;TBXA2R)contributestomorphologicalchangesthroughactivationofkinases.Plateletadhesion,cyotoskeletalreorganization,secretion,andamplificationloopsarealldifferentstepstowardstheformationofaplatelet-plug.ThesecascadesresultintheactivationoftheFibrinogenReceptorexpressedonplateletcells.Thisactivationdevelopsbindingsitesforfibrinogen,whicharenotavailableininactiveplatelets.Thebindingoffibrinogenresultsinthelinkageofactivatedplateletsthroughfibrinogenbridges,therebymediatingaggregation.InhibitionofthisreceptorthroughGlycoproteinIIb/IIIainhibitorsblocksplateletaggregationinducedbyanyagonist.59血液专业知识培训InducersofplateletaggregationADPLowdose1streversiblephaseHighdose2ndirreversiblephaseThromboxaneA2(TXA2)CollagenThrombin60血液专业知识培训PhospholipidArachidonicAcidPhospholipaseA2TXA2Cyclo-oxygenasePGG2&PGH2PGI2Prostacyclinsynthase(Vascularendothelium)Thromboxanesynthase(Platelets)AggregationAnti-aggregationContractionRelaxation61血液专业知识培训Plateletinteractionswithagonistsandantagonistsofplateletaggregation,thevesselwall,otherplatelets,andadhesivemacromolecules.Agentsinparenthesespreventtheformationorinhibitthefunctionoftheadjacentagonistsofplateletaggregation.ADP=adenosinediphosphate,VWF=vonWillebrandfactor,cAMP=cyclicadenosinemonophosphate,GP=glycoprotein.62血液专业知识培训3.Releaseorsecretion:PlateletscontainalphaanddensegranulesDensegranules:containingADPorATP,calcium,andserotonin-granules:containingplateletfactor4,PDGF,fibronectin,B-thromboglobulin,vWF,fibrinogen,andcoagulationfactorsVandXIII63血液专业知识培训Schematicdrawingoftheplatelet(topfigure),showingitsalphaanddensegranulesandcanalicularsystem.Thebottomfigureillustratestheplateletsmajorfunctions,includingsecretionofstoredproducts,aswellasitsattachment,viaspecificsurfaceglycoproteins(GP),todenudedepithelium(bottom)andotherplatelets(left).VWF:vonWillebrandfactor;TSP:thrombospondin;PF4:plateletfactor4;PDGF:plateletderivedgrowthfactor;-TG:betathromboglobulin;ADP:adenosinediphosphate;ATP:adenosinetriphosphate.64血液专业知识培训Aschematicrepresentationofselectedplateletresponsestoactivationandthecongenitaldisordersofplateletfunction.AC=adenylylcyclase;BSS=BernardSouliersyndrome;CO=cyclooxygenase;DG=diacylglycerol;G=GTP-bindingprotein;IP3=inositoltrisphosphate;MLC=myosinlightchain;MLCK=myosinlightchainkinase;P2Y1,P2Y12=G-protein-coupledADPreceptors;PAF=plateletactivatingfactor;PGG2/PGH2=prostaglandinarachidonicpathwayintermediates;PIP2=phosphatidylinositolbisphosphate;PKC=proteinkinaseC;PLA2=phospholipaseA2;TK=tyrosinekinase;PLC=phospholipaseC;TS=thromboxanesynthase;TxA2=thromboxaneA2;vWD=vonWillebranddisease;vWF=vonWillebrandfactor.TheRomannumeralsinthecirclesrepresentcoagulationfactorsandyellowPsindicatephosphorylation.(Modified with permission from Rao AK:Congenital disorders of platelet function:disorders of signal transduction and secretion.Am J Med Sci 1998;316:69-76.)65血液专业知识培训4.ContractionClotretraction(血块回缩)66血液专业知识培训5.AdsorptionClottingfactors:I,V,XI,XIII67血液专业知识培训Production ofPlatelets(Thrombocytes)FormationLargemultinucleatedcellsthatpushesagainstthewallofthecapillaryCytoplasmicextensionsstickthroughandseparate68血液专业知识培训ThrombopoietinThrombopoietin(leukemiavirusoncogeneligand,megakaryocytegrowthanddevelopmentfactor),isaglycoproteinhormoneproducedmainlybytheliverandthekidneythatregulatestheproductionofplateletsbythebonemarrowItstimulatestheproductionanddifferentiationofmegakaryocytes,thebonemarrowcellsthatfragmentintolargenumbersofplatelets69血液专业知识培训70血液专业知识培训71血液专业知识培训Hemostasis（止血）Thearrestofbleedingfollowinginjuryandtheresultof3interacting,overlappingmechanisms:Vascularspasm（血管收缩）（血管收缩）Formationofaplateletplug（血小板血栓形成）（血小板血栓形成）Bloodcoagulation(clotting)（血液凝固）（血液凝固）Bleedingtime(出血时间)：9min72血液专业知识培训73血液专业知识培训74血液专业知识培训RoleofvascularendotheliuminhemostasisoVasoconstriction:reducedbloodflowfacilitatescontactactivationofplateletsandcoagulationfactorsoExposureofsub-endothelialbasementmembraneandcollagenoReleaseoftissuethromboplastins(组织因子组织因子)oSynthesisofbasementmembranecomponents,tissuefactor(组织因子组织因子),vWF,plasminogenactivator(纤溶酶原激活物纤溶酶原激活物),antithrombinIII(抗凝血抗凝血酶酶III),thrombomodulin(血栓调节蛋白血栓调节蛋白)75血液专业知识培训Signalingmediatesresponsestodamageinabloodvessel:adjacentendothelialcellsareasourceofsignalsthatinfluenceplateletaggregationandalterbloodflowandclotformationattheaffectedsite.76血液专业知识培训RoleofplateletsinhemostasisReleaseofvasoconstrictingsubstancesFormationoftheplateletplugPromotionofbloodclottingClotretraction77血液专业知识培训ClottingfactorsClottingfactorSynonymsIfibrinogen纤维蛋白原IIprothrombin凝血酶原IIItissuethromboplastin组织因子IVCa2+Vproaccelerin前加速素易变因子VIIproconvertin前转变素稳定因子VIIIantihemophilicfactor抗血友病因子IXplasmathromboplastincomponent血浆凝血活酶XStuart-ProwerfactorXIplasmathromboplastinantecedent血浆凝血活酶前质XIIcontactfactor接触因子XIIIfibrin-stabilizingfactor纤维蛋白稳定因子uBloodcoagulation78血液专业知识培训79血液专业知识培训Theliverplaysacriticalroleinproducingandmodifyingblood-borneproteins,includingthoseusedintheclottingpathway.Moreover,bilesaltsfromtheliverfacilitatetheabsorptionoflipidsinthediet,includingvitaminK,whichisrequiredforthesynthesisofprothrombin.80血液专业知识培训CoagulationfactorsandrelatedsubstancesNumberand/ornameFunctionI(fibrinogen)Formsclot(fibrin)II(prothrombin)Itsactiveform(IIa)activatesI,V,VII,VIII,XI,XIII,proteinC,plateletsTissuefactorCo-factorofVIIa(formerlyknownasfactorIII)CalciumRequiredforcoagulationfactorstobindtophospholipid(formerlyknownasfactorIV)V(proaccelerin,labilefactor)Co-factorofXwithwhichitformstheprothrombinasecomplexVIUnassignedoldnameofFactorVaVII(stablefactor)ActivatesIX,XVIII(antihemophilicfactor)Co-factorofIXwithwhichitformsthetenasecomplexIX(Christmasfactor)ActivatesX:formstenasecomplexwithfactorVIIIX(Stuart-Prowerfactor)ActivatesII:formsprothrombinasecomplexwithfactorVXI(plasmathromboplastinantecedent)ActivatesIXXII(Hagemanfactor)ActivatesfactorXIandprekallikreinXIII(fibrin-stabilizingfactor)CrosslinksfibrinvonWillebrandfactorBindstoVIII,mediatesplateletadhesionprekallikreinActivatesXIIandprekallikrein;cleavesHMWKhigh-molecular-weightkininogen(HMWK)SupportsreciprocalactivationofXII,XI,andprekallikreinfibronectinMediatescelladhesionantithrombinIIIInhibitsIIa,Xa,andotherproteases;heparincofactorIIInhibitsIIa,cofactorforheparinanddermatansulfate(minorantithrombin)proteinCInactivatesVaandVIIIaproteinSCofactorforactivatedproteinC(APC,inactivewhenboundtoC4b-bindingprotein)proteinZMediatesthrombinadhesiontophospholipidsandstimulatesdegradationoffactorXbyZPIProteinZ-relatedproteaseinhibitor(ZPI)DegradesfactorsX(inpresenceofproteinZ)andXI(independently)plasminogenConvertstoplasmin,lysesfibrinandotherproteinsalpha2-antiplasminInhibitsplasmintissueplasminogenactivator(tPA)ActivatesplasminogenurokinaseActivatesplasminogenplasminogenactivatorinhibitor-1(PAI1)InactivatestPA&urokinase(endothelialPAI)plasminogenactivatorinhibitor-2(PAI2)InactivatestPA&urokinase(placentalPAI)cancerprocoagulantPathologicalfactorXactivatorlinkedtothrombosisincancer81血液专业知识培训Explorationofthedetailsoftheclottingpathwayhasyieldeddetailedinformationaboutthesequence,onlyaportionofwhichisrepresentedhere.Notethrombinsinfluenceinthreedifferentdirections.82血液专业知识培训Knowledgethatthrombinplaysacentralroleinclottinghasgenerateddetailedstudiesofthepossiblepathwaysresultinginitsformation:theextrinsicpathwayisthemoreimportantofthetwoundermostcircumstances.83血液专业知识培训Coagulationcascade3processes2pathways84血液专业知识培训85血液专业知识培训Tissuefactorpathway(extrinsic)Followingdamagetothebloodvessel,endotheliumTissueFactor(TF)isreleased,formingacomplexwithFVIIandinsodoing,activatingit(TF-FVIIa).TF-FVIIaactivatesFIXandFX.FVIIisitselfactivatedbythrombin,FXIa,plasmin,FXIIandFXa.TheactivationofFXabyTF-FVIIaisalmostimmediatelyinhibitedbytissuefactorpathwayinhibitor(TFPI).FXaanditsco-factorFVaformtheprothrombinasecomplex,whichactivatesprothrombintothrombin.Thrombinthenactivatesothercomponentsofthecoagulationcascade,includingFVandFVIII(whichactivatesFXI,which,inturn,activatesFIX),andactivatesandreleasesFVIIIfrombeingboundtovWF.FVIIIaistheco-factorofFIXa,andtogethertheyformthetenasecomplex,whichactivatesFX;andsothecyclecontinues.(Tenaseisacontractionoftenandthesuffix-aseusedforenzymes.)86血液专业知识培训Contactactivationpathway(intrinsic)Thecontactactivationpathwaybeginswithformationoftheprimarycomplexoncollagenbyhigh-molecular-weightkininogen(HMWK),prekallikrein,andFXII(Hagemanfactor).PrekallikreinisconvertedtokallikreinandFXIIbecomesFXIIa.FXIIaconvertsFXIintoFXIa.FactorXIaactivatesFIX,whichwithitsco-factorFVIIIaformthetenasecomplex,whichactivatesFXtoFXa.TheminorrolethatthecontactactivationpathwayhasininitiatingclotformationcanbeillustratedbythefactthatpatientswithseveredeficienciesofFXII,HMWK,andprekallikreindonothaveableedingdisorder.87血液专业知识培训FinalcommonpathwayThrombinhasalargearrayoffunctionsItsprimaryroleistheconversionoffibrinogentofibrin,thebuildingblockofahemostaticplug.Inaddition,itactivatesFactorsVIIIandVandtheirinhibitorproteinC(inthepresenceofthrombomodulin),anditactivatesFactorXIII,whichformscovalentbondsthatcrosslinkthefibrinpolymersthatformfromactivatedmonomers.Followingactivationbythecontactfactorortissuefactorpathways,thecoagulationcascadeismaintainedinaprothromboticstatebythecontinuedactivationofFVIIIandFIXtoformthetenasecomplex,untilitisdown-regulatedbytheanticoagulantpathways.88血液专业知识培训89血液专业知识培训FibrinPolymerization Structure of Fibrinogen90血液专业知识培训Adeficiencyofaclottingfactorcanleadtouncontrolledbleeding.VitaminKisacofactorneededforthesynthesisoffactorsII,VII,IX,&Xintheliver.SoadeficiencyofVitaminKpredisposestobleeding.91血液专业知识培训Hemophilia&BolshevikRevolutionhttp:/en.wikipedia.org