医学教学课件：BLOOD血液

BLOOD【血液】2ObjectivesAfterstudyingthispart,youshouldbeableto:describethecomponentsofblood,theirorigins,andtheroleofhemoglobinintransportingoxygeninredbloodcells.understandthemolecularbasisofbloodgroupsandthereasonsfortransfusionreactions.delineatetheprocessofhemostasisthatrestrictsbloodlosswhenvesselsaredamaged,andtheadverseconsequencesofintravascularthrombosis.understandthebasisofdiseasestateswherecomponentsofthebloodareabnormal,dysregulated,orboth.3Plasma（血浆）BloodCellsRedBloodCells(RBC)orErythrocytes（红细胞）WhiteBloodCells(WBC)orLeucocytes（白细胞）Platelets(PLT)orThrombocytes（血小板）Componentsofblood5PlasmaThefluidportionoftheblood,theplasma,isaremarkablesolutioncontaininganimmensenumberofions,inorganicmolecules,andorganic

moleculesthatareintransittovariouspartsofthebodyoraidinthetransportofothersubstancesNormalplasmavolumeisabout5%ofbodyweight,orroughly3500mLina70-kgmanPlasmaclotsonstanding,remainingfluidonlyifananticoagulantisaddedIfwholebloodisallowedtoclotandtheclotisremoved,theremainingfluidiscalledserumSerumhasessentiallythesamecompositionasplasma,exceptthatitsfibrinogenandclottingfactorsII,V,andVIIIhavebeenremovedandithasahigherserotonincontentbecauseofthebreakdownofplateletsduringclotting6SystemforNamingBlood-ClottingFactorsFactorNamesIFibrinogenIIProthrombinIIIThromboplastinIVCalciumVProaccelerin,labilefactor,acceleratorglobulinVIIProconvertin,SPCA,stablefactorVIIIAntihemophilicfactor(AHF),antihemophilicfactorA,antihemophilicglobulin(AHG)IXPlasmathromboplasticcomponent(PTC),Christmasfactor,antihemophilicfactorBXStuart–ProwerfactorXIPlasmathromboplastinantecedent(PTA),antihemophilicfactorCXIIHagemanfactor,glassfactorXIIIFibrin-stabilizingfactor,Laki–LorandfactorHMW-KHigh-molecular-weightkininogen,FitzgeraldfactorPre-KaPrekallikrein,FletcherfactorKaKallikreinPLPlateletphospholipid7SomeoftheProteinsSynthesizedbytheLiver:PhysiologicFunctionsandPropertiesNamePrincipalFunctionBindingCharacteristicsSerumorPlasmaConcentrationAlbuminBindingandcarrierprotein;osmoticregulatorHormones,aminoacids,steroids,vitamins,fattyacids4500–5000mg/dLOrosomucoidUncertain;mayhavearoleininflammationTrace;risesininflammationα1-AntiproteaseTrypsinandgeneralproteaseinhibitorProteasesinserumandtissuesecretions1.3–1.4mg/dLα-FetoproteinOsmoticregulation;bindingandcarrierproteinaHormones,aminoacidsFoundnormallyinfetalbloodα2-MacroglobulinInhibitorofserumendoproteasesProteases150–420mg/dLAntithrombin-IIIProteaseinhibitorofintrinsiccoagulationsystem1:1bindingtoproteases17–30mg/dLCeruloplasminTransportofcopperSixatomscopper/mol15–60mg/dLC-reactiveproteinUncertain;hasroleintissueinflammationComplementC1q<1mg/dL;risesininflammationFibrinogenPrecursortofibrininhemostasis200–450mg/dLHaptoglobinBinding,transportofcell-freehemoglobinHemoglobin1:1binding40–180mg/dLHemopexinBindstoporphyrins,particularlyhemeforhemerecycling1:1withheme50–100mg/dLTransferrinTransportofironTwoatomsiron/mol3.0–6.5mg/dLApolipoproteinBAssemblyoflipoproteinparticlesLipidcarrierAngiotensinogenPrecursortopressorpeptideangiotensinIIProteins,coagulationfactorsII,VII,IX,XBloodclotting20mg/dLAntithrombinC,proteinCInhibitionofbloodclottingInsulinlikegrowthfactorIMediatorofanaboliceffectsofgrowthhormoneIGF-IreceptorSteroidhormone-bindingglobulinCarrierproteinforsteroidsinbloodstreamSteroidhormones3.3mg/dLThyroxine-bindingglobulinCarrierproteinforthyroidhormoneinbloodstreamThyroidhormones1.5mg/dLTransthyretin(thyroid-bindingprealbumin)CarrierproteinforthyroidhormoneinbloodstreamThyroidhormones25mg/dL11Plasmaincludeswater,ions,proteins,nutrients,hormones,wastes,etc.Thehematocrit（血细胞比容）

isa

rapidassessment

ofbloodcomposition.

Itisthepercentofthe

bloodvolumethatis

composedofRBCs

(redbloodcells).

thevolumeofredbloodcellsasapercentageofcentrifugedwholeblood M:40~50% F:37~48%Hematocrit（packedcellvolume,血细胞比容）InternationalCouncilforStandardizationinHaematology(ICSH)Recommendationsfor"SurrogateReference"MethodforthePackedCellVolume13BoneMarrowIntheadult,redbloodcells,manywhitebloodcells,andplateletsareformedinthebonemarrowInthefetus,bloodcellsarealsoformedintheliverandspleen,andinadultssuchextramedullaryhematopoiesismayoccurindiseasesinwhichthebonemarrowbecomesdestroyedorfibrosedChangesinredbonemarrowcellularityinvariousboneswithage14NormalValuesfortheCellularElementsinHumanBloodCellCells/μL(average)ApproximateNormalRangePercentageofTotalWhiteCellsTotalwhitebloodcells90004000–11,000…Granulocytes

Neutrophils54003000–600050–70

Eosinophils275150–3001–4

Basophils350–1000.4Lymphocytes27501500–400020–40Monocytes540300–6002–8Erythrocytes

Females4.8×106……

Males5.4×106……Platelets300,000200,000–500,000…15Developmentofvariousformedelementsofthebloodfrombonemarrowcells16Whitebloodcells(Leucocytes)

（白细胞）17Platelets(Thrombocytes)血小板Plateletsaresmall,granulatedbodiesthataggregateatsitesofvascularinjuryTheylacknucleiandare2–4μmindiameterThereareabout300,000/μLofcirculatingblood,andtheynormallyhaveahalf-lifeofabout4daysThemegakaryocytes,giantcellsinthebonemarrow,formplateletsbypinchingoffbitsofcytoplasmandextrudingthemintothecirculationBetween60and75%oftheplateletsthathavebeenextrudedfromthebonemarrowareinthecirculatingblood,andtheremainderaremostlyinthespleenSplenectomycausesanincreaseintheplateletcount(thrombocytosis)18PhysiologicalpropertiesofplateletsAdhesion19PhysiologicalpropertiesofplateletsAggregation20PhysiologicalpropertiesofplateletsReleaseorsecretion21PhysiologicalpropertiesofplateletsContraction22Redbloodcells(Erythrocytes)（红细胞）Theredbloodcells(erythrocytes)carryhemoglobininthecirculationTheyarebiconcavedisksthataremanufacturedinthebonemarrowInmammals,theylosetheirnucleibeforeenteringthecirculationInhumans,theysurviveinthecirculationforanaverageof120daysTheaveragenormalredbloodcellcountis5.4million/μLinmenand4.8million/μLinwomenThenumberofredcellsisalsoconvenientlyexpressedasthehematocrit,orthepercentageoftheblood,byvolume,thatisoccupiedbyerythrocytes.Eachhumanredbloodcellisabout7.5μmindiameterand2μmthick,andeachcontainsapproximately29pgofhemoglobinTherearethusabout3×1013redbloodcellsandabout900gofhemoglobininthecirculatingbloodofanadultman23Humanredbloodcellsandfibrinfibrils24Redcellformationanddestruction25RoleoftheSpleenThespleenisanimportantbloodfilterthatremovesagedorabnormalredcellsItalsocontainsmanyplateletsandplaysasignificantroleintheimmunesystemAbnormalredcellsareremovediftheyarenotasflexibleasnormalredcellsandconsequentlyareunabletosqueezethroughtheslitsbetweentheendothelialcellsthatlinethesplenicsinuses26HemoglobinThered,oxygen-carryingpigmentintheredbloodcellsofvertebratesishemoglobin,aproteinwithamolecularweightof64,45027ReactionsofHemoglobin28HemoglobinintheFetusThebloodofthehumanfetusnormallycontainsfetalhemoglobin(hemoglobinF)ItsstructureissimilartothatofhemoglobinAexceptthattheβchainsarereplacedbyγchains;thatis,hemoglobinFisα2γ2Fetalhemoglobinisnormallyreplacedbyadulthemoglobinsoonafterbirth29BloodTypesThemembranesofhumanredcellscontainavarietyofbloodgroupantigens,whicharealsocalledagglutinogens(凝集原)ThemostimportantandbestknownofthesearetheAandBantigens,buttherearemanymore30AntigensoftheABOsystemonthesurfaceofredbloodcells31SummaryofABOSystemBloodTypeAgglutininsinPlasmaFrequencyinUnitedStates%PlasmaAgglutinatesRedCellsofType:OAnti-A,anti-B45A,B,ABAAnti-B41B,ABBAnti-A10A,ABABNone4None32TheRhGroupAsidefromtheantigensoftheABOsystem,thoseoftheRhsystemareofthegreatestclinicalimportanceTheRhfactor,namedfortherhesusmonkeybecauseitwasfirststudiedusingthebloodofthisanimal,isasystemcomposedprimarilyoftheC,D,andEantigens,althoughitactuallycontainsmanymoreUnliketheABOantigens,thesystemhasnotbeendetectedintissuesotherthanredcellsDisbyfarthemostantigeniccomponent,andthetermRh-positiveasitisgenerallyusedmeansthattheindividualhasagglutinogenDTheDproteinisnotglycosylated,anditsfunctionisunknownTheRh-negativeindividualhasnoDantigenandformstheanti-DagglutininwheninjectedwithD-positivecellsTheRhtypingserumusedinroutinebloodtypingisanti-DserumEighty-fivepercentofCaucasiansareD-positiveand15%areD-negative;over99%ofAsiansareD-positiveUnliketheantibodiesoftheABOsystem,anti-DantibodiesdonotdevelopwithoutexposureofaD-negativeindividualtoD-positiveredcellsbytransfusionorentranceoffetalbloodintothematernalcirculationD-negativeindividualswhohavereceivedatransfusionofD-positiveblood(evenyearspreviously)canhaveappreciableanti-DtitersandthusmaydeveloptransfusionreactionswhentransfusedagainwithD-positiveblood33HemolyticDiseaseoftheNewborn34HemostasisHemostasisistheprocessofformingclotsinthewallsofdamagedbloodvesselsandpreventingbloodlosswhilemaintainingbloodinafluidstatewithinthevascularsystemAcollectionofcomplexinterrelatedsystemicmechanismsoperatestomaintainabalancebetweencoagulationandanticoagulation35Summaryofreactionsinvolvedinhemostasis36TheClottingMechanism37AnticlottingMechanismsThetendencyofbloodtoclotisbalancedinvivobyreactionsthatpreventclottinginsidethebloodvessels,breakdownanyclotsthatdoform,orbothThesereactionsincludetheinteractionbetweentheplatelet-aggregatingeffectofthromboxaneA2andtheantiaggregatingeffectofprostacyclin,whichcausesclotstoformatthesitewhenabloodvesselisinjuredbutkeepsthevessellumenfreeofclot38ExamplesofDiseasesDuetoDeficiencyofClottingFactorsDeficiencyofFactor:ClinicalSyndromeCauseIAfibrinogenemia无纤维蛋白原血症Depletionduringpregnancywithprematureseparationofplacenta;alsocongenital(rare)IIHypoprothrombinemia(hemorrhagictendencyinliverdisease)低凝血酶原血症Decreasedhepaticsynthesis,usuallysecondarytovitaminKdeficiencyVParahemophilia副血友病CongenitalVIIHypoconvertinemiaCongenitalVIIIHemophiliaA(classichemophilia)甲型血友病CongenitaldefectduetovariousabnormalitiesofthegeneonXchromosomethatcodesforfactorVIII;diseaseisthereforeinheritedasasex-linkedcharacteristicIXHemophiliaB(Christmasdisease)CongenitalXStuart–ProwerfactordeficiencyCongenitalXIPTAdeficiencyCongenitalXIIHagemantraitCongenital39AnticlottingMechanismsAntithrombinIIIisacirculatingproteaseinhibitorthatbindstoserineproteasesinthecoagulationsystem,blockingtheiractivityasclottingfactors.Thisbindingisfacilitatedbyheparin,anaturallyoccurringanticoagulantthatisamixtureofsulfatedpolysaccharides.TheclottingfactorsthatareinhibitedaretheactiveformsoffactorsIX,X,XI,andXIITheendotheliumofthebloodvesselsalsoplaysanactiveroleinpreventingtheextensionofclots.Allendothelialcellsexceptthoseinthecerebralmicrocirculationproducethrombomodulin,athrombin-bindingprotein,ontheirsurfaces.Incirculatingblood,thrombinisaprocoagulantthatactivatesfactorsVandVIII,butwhenitbindstothrombomodulin,itbecomesananticoagulantinthatthethrombomodulin–thrombincomplexactivatesproteinC.ActivatedproteinC(APC),alongwithitscofactorproteinS,inactivatesfactorsVandVIIIandinactivatesaninhibitoroftissueplasminogenactivator,increasingtheformationofplasminPlasmin(fibrinolysin)istheactivecomponentoftheplasminogen(fibrinolytic)system40ThefibrinolyticsystemanditsregulationbyproteinC41AnticoagulantsHeparinisanaturallyoccurringanticoagulantthatfacilitatestheactionofantithrombinIII.Low-molecular-weightfragmentshavebeenproducedfromunfractionatedheparin,andtheseareseeingincreasedclinicalusebecausetheyhavealongerhalf-lifeandproduceamorepredictableanticoagulantresponsethanunfractionatedheparin.ThehighlybasicproteinprotamineformsanirreversiblecomplexwithheparinandisusedclinicallytoneutralizeheparinInvivo,aplasmaCa2+levellowenoughtointerferewithbloodclottingisincompatiblewithlife,butclottingcanbepreventedinvitroifCa2+isremovedfromthebloodbytheadditionofsubstancessuchasoxalates,whichforminsolublesaltswithCa2+,orchelatingagents,whichbindCa2+Coumarinderivatives(香豆素类)suchasdicumarolandwarfarinarealsoeffectiveanticoagulants.TheyinhibittheactionofvitaminK,whichisanecessarycofactorfortheenzymethatcatalyzestheconversionofglutamicacidresiduestoγ-carboxyglutamicacidresidues.Sixoftheproteinsinvolvedinclottingrequireconversionofanumberofglutamicacidresiduestoγ-carboxyglutamicacidresiduesbeforebeingreleasedintothecirculation,andhenceallsixarevitaminK-dependent.TheseproteinsarefactorsII(prothrombin),VII,IX,andX,proteinC,andproteinS42SummaryBloodcells;plasmaBloodcellsariseinthebonemarrowandaresubjecttoregularrenewal;themajorityofplasmaproteinsaresynthesizedbytheliverHemoglobin;fetalhemoglobin;mutatedformsofhemoglobinleadtoredcellabnormalitiesandanemiaBloodgroupsystemsHemostasisClottingmechasnismAnticlottingmechanismsAnticoagulants43Whichofthefollowingstatementsiscorrect?ADamagedtissuereleasesasubstancecalledtissuefibrinogen,whichismainlycomposedofphospholipidsBDamagetothevesselwallinitiateswhatiscalledtheintrinsicpathwayCTheactivationofproteincoagulationfactorplusthereleaseofplateletthromboplastineventuallyleads