分析报告ppt课件.ppt

Inpeopleacclimatedtohighaltitudes theconcentrationof2 3 diphosphoglycerate 2 3 DPG inthebloodisincreased whichallowstheseindividualstodeliveralargeramountofoxygentotissuesunderconditionsofloweroxygentension InitiallygivenhighdoseO2throughmaskElectrontransportBecausetherearemanymoreoxygenmoleculespresentinagivenvolumewhenunderpressure hyperbaricoxygendissolvesinthebloodinfargreateramountsenablingittobetransportedtothecells Hyperbaricoxygen HBO alsohelpsridhaemoglobinofthetenaciousCOmolecules freeingitupfornormaluseoncemore Theactualamountofoxygenmoleculesatapressureof3ata 20msw inafixedvolumeisequalto3timestheamountatthesurface Incasesofcarbonmonoxidepoisoning itnormallytakesoverfourhoursfortheamountofCOinthebodytofallbyonehalf duringwhichtimethetissuesarehypoxicduetoreplacementofO2HbwithCOHb Hyperbaricoxygenat3atareducesthisto20minutes duringwhichtimetheextraoxygendissolvedinthebloodalleviateshypoxia Prostaglandinsactinamannersimilartothatofhormones bystimulatingtargetcellsintoaction differfromhormonesinthattheyactlocally neartheirsiteofsynthesis andtheyaremetabolizedveryrapidlythesameprostaglandinsactdifferentlyindifferenttissues Hemostasis Thrombosis HemophiliaBethA BouchardBIOC212 BiochemistryofHumanDiseaseSpring2005 HEMOSTASIS 1 INITIATIONVesselwall endothelialcellsandsubendothelialcomponents2 LOCALIZATIONPlatelets circulatingcellularelements3 PROPAGATION AMPLIFICATIONPlasmacoagulationproteins factors 4 TERMINATIONPlasmacoagulationproteininhibitors5 ELIMINATIONFibrinolyticsystem BLOODCOAGULATION BLOODCOAGULATION CONT Deficienciesinallofthefactors exceptfactorXII leadtoableedingtendencyintheaffectedindividualDescribedasa waterfall or cascade sequenceofzymogen pro enzyme toenzymeconversions witheachenzymeactivatingthenextzymogenintheseqeunceActivatedfactorenzymesaredesignatedwithan a e g factorXa Commonconstituentsofcoagulationcomplexes VitaminK dependent VKD zymogen Ca2 Appropriatemembranesurface activatedplatelets VIIIa IXacomplex Va Xacomplex subendothelialcells typicallyfibroblasts TF VIIacomplex Proteincofactor Commonconstituentsofcoagulationcomplexes VitaminK dependent VKD zymogen Ca2 Appropriatemembranesurface activatedplatelets VIIIa IXacomplex Va Xacomplex subendothelialcells typicallyfibroblasts TF VIIacomplex Proteincofactor FunctionalDomainsoftheVitaminK dependentZymogens Gamma g carboxyglutamicacid VITAMINK Groupofrelated fatsolublecompounds whichdifferinthenumberofside chainisoprenoidunitsPlantderived vitaminK1 andsynthesizedbyintestinalbacteria vitaminK2 ThereducedformofvitaminK2 vitaminKH2 isrequiredforthepost translational gamma carboxylationofseveralproteinsinvolvedinbloodclotting FormationofGlaresiduessubsequenttoproteinsynthesis post translational VitaminKdeficiency DeficiencyofvitaminKisrarebecauseofitswidedistributioninnature anditsproductionbyintestinalbacteriaFoundinindividualswithliverdiseaseandfatmalabsorption itisassociatedwithbleedingdisordersNewborninfants especiallypreemies arealsoatrisk PlacentaisinsufficientinthetransferofmaternalvitaminK ConcentrationofcirculatingvitaminKdropsimmediatelyafterbirth anditrecoversuponabsorptionoffood GutofthenewbornissterileThus newbornsaregivenaninjectionofvitaminKfollowingbirth Commonconstituentsofcoagulationcomplexes VitaminK dependent VKD zymogen Proteincofactor Ca2 Appropriatemembranesurface activatedplatelets VIIIa IXacomplex Va Xacomplex subendothelialcells typicallyfibroblasts TF VIIacomplex Relevanceofcomplexformationanditsconstituents Commonconstituentsofcoagulationcomplexes VitaminK dependent VKD zymogen Proteincofactor Ca2 Appropriatemembranesurface activatedplatelets VIIIa IXacomplex Va Xacomplex subendothelialcells typicallyfibroblasts TF VIIacomplex Expressanionicphospholipidsandmembranereceptorsforcoagulationproteins Inplatelets theexpressionofthismembranesurfaceisactivation dependent ThrombinCleavesFibrinogenActivatesPlateletsActivatesprocofactors FVandFVIII Activateszymogens FVII FXIandFXIII IntrinsicPathwayofBloodCoagulation NofactorsextrinsictothebloodareinvolvedClinicaltesttoassessthefunctionalityofthispathwayistheactivatedpartialthromboplastintime aPTT KaolinandcephalinareaddedtothetestplasmasampleThenormalrangeis 30 50seconds variesslightlydependingonthelaboratory ProlongationsintheaPTTareobservedindeficienciesoffactorsXI IX VIII X andV prothrombin orfibrinogen Usedtotestforcommoncongenitalhemophilias deficienciesinIX VIII orXI andtomonitorheparintreatment ExtrinsicPathwayofBloodCoagulation Extrinsicreferstotissuefactor whichisexpressedonsubendothelialcellsClinicaltesttoassessthefunctionalityofthispathwayistheprothrombintime PT LipidatedtissuefactorisaddedtotestplasmasampleThenormalrangeis 10 15seconds variesslightlydependingonthelaboratory ProlongationsinthePTareobservedindeficienciesoffactorsVII X V prothrombin orfibrinogen Usedtotestfortherarecongenitaldeficienciesinthesefactors MoreoftenitisusedtodiagnoseacquiredbleedingdisordersresultingfromvitaminKdeficiency oralanticoagulants e g warfarin andliverdisease ThrombinTime TT Inthistest thrombinisaddedtoplasmaThenormalrangeis 10 15seconds variesslightlydependingonthelaboratory ProlongationsintheTTareobservedincongenitalfibrinogendeficiencyoracquiredfibrinogendeficiencyresultingfromconsumptionoffibrinogeninDIC disseminatedintravascularcoagulation ormayoccurfollowingtreatmentwithfibrinolyticdrugs HemophiliasAandB HemophiliasAandBarecausebydeficienciesinfactorsVIIIorIX respectivelyAffect 1in10 000malesInheritedasarecessiveX linkedtrait Momwouldbeanunaffectedcarrier TreatedbyadministrationoffactorVIIIorfactorIXconcentratesRecombinantfactorVIIIorXIGenetherapytrials HEMOSTASIS CONT 1 INITIATIONVesselwall endothelialcellsandsubendothelialcomponents2 LOCALIZATIONPlatelets circulatingcellularelements3 PROPAGATION AMPLIFICATIONPlasmacoagulationproteins factors 4 TERMINATIONPlasmacoagulationproteininhibitors5 ELIMINATIONFibrinolyticsystem INHIBITORS INHIBITORS cont FIBRINOLYSIS FIBRINOLYSIS CONT Bleedingdisorderscanspanthespectrumfromweepingbloodvesselstofull fledgedinternalandexternalhemorrhage Geneticdefects plateletabnormalitiesbloodvesselwallabnormalitiesclottingfactordeficiencies hemophilias excessclotbreakdown fibrinolysis Acquireddefects liverdisease siteofclottingfactorsynthesis vitaminKdeficiencyautoimmunedisease plateletdestruction trauma Bleedingdisorderscanspanthespectrumfromweepingbloodvesselstofull fledgedinternalandexternalhemorrhage Treatedbyfactorreplacement Thrombosiscanbemanifestedasatransient short termorepisodiceventinindividualswithchronicorrecurringclotting Itisthemajorcauseofbothstrokeandheartattacks Geneticdefects clottingfactorINHIBIT