肝功能损害与Sepsis管向东资料

肝功能损害与Sepsis管向东文档ppt肝脏的生理功能肝脏的生理功能（一）代谢功能糖类：肝糖原贮存、分解、糖异生脂类：脂肪、胆固醇及磷脂蛋白质：血清总蛋白、白蛋白血浆凝血因子几乎全部在肝脏合成肝脏的生理功能（二）分泌和排泄功能（三）生物转化：解毒作用（四）免疫防御肝功能状态的判断HepaticFailureDefinition:Lossoffunctionallivercellmassbelowacriticallevelresultsinliverfailure(acuteorcomplicatingachronicliverdisease)Resultsin:hepaticencephalopathy&Coma,Jaundice,cholestasis,ascites,bleeding,renalfailure,deathAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.HepaticFailureProductionofEndogenousToxins&DrugmetabolicFailureBileAcids,Bilirubin,Prostacyclins,NO,Toxicfattyacids,Thiols,Indol-phenolmetabolitesThesetoxinscausefurthernecrosis/apoptosisandaviciouscycleDetrimentaltorenal,brainandbonemarrowfunction;resultsinpoorvasculartoneAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.ICU内

如何迅速判断重症病人肝脏功能?（一）意识状态清醒？谵妄？昏睡、昏迷？原因：肝性脑病脑水肿其他脑水肿机制渗透性异常血氨、谷氨酰胺脑血流减慢血管舒张、脑代谢减慢AndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.肝性脑病发病机制氨中毒学说GABA/苯二氮卓类受体复合物学说支链氨基酸和假神经递质学说5-羟色胺学说锌/锰学说W.J.Cash,P.Mcconville,etal.CurrentconceptsintheassessmentandtreatmentofHepaticEncephalopathy.QJMed;103:9–16.其他原因内环境异常------由肝功能异常导致:组织灌注不足：局部/系统血流动力学异常代谢紊乱：电解质/酸碱平衡紊乱（二）凝血功能障碍凝血因子产生减少血浆凝血因子几乎全部在肝脏合成MarcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222凝血因子减少MarcelLevi,StevenMOpal.CriticalCare2006,10:222TESTRESULTSCAUSEPT延长，APTT正常VII因子缺乏轻度VitK缺乏少量VitK拮抗剂PT正常，APTT延长VII、IX、XI因子缺乏使用非小分子肝素抑制剂抗体和/或抗磷脂抗体XII因子和前激肽释放酶缺乏PT、APTT均延长X、V、II因子缺乏VitK严重缺乏VitK拮抗剂全部凝血因子缺乏血小板减少MarcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222（三）乳酸主要在肝脏代谢（>90%）糖酵解产物NicolaosF.Madias.Lacticacidosis.KidneyInternational,Vol.29(1986),752-774.DanielDeBacker.Lacticacidosis.IntensiveCareMed(2003)29:699–702乳酸水平升高的原因氧需求增加组织缺氧肝衰竭药物毒物特殊疾病:糖尿病NicolaosF.Madias.Lacticacidosis.KidneyInternational,Vol.29(1986),752-774.乳酸&脓毒症乳酸清除率—早期提示组织缺氧程度并与死亡率相关（severesepsisandsepticshock）H.BryantNguyen,EmanuelP.Rivers,etal.Earlylactateclearanceisassociatedwithimprovedoutcomeinseveresepsisandsepticshock.CritCareMed2004;32:1637–1642乳酸&急性肝脏衰竭WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63乳酸&预后WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63乳酸&发病率、死亡率(肝叶切除术后)预测发病率和死亡率IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8乳酸与ICU住院时间IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8（四）酸碱平衡酸中毒:

乳酸碱中毒:

低白蛋白血症（碱化血浆）Georg-ChristianFunk,DanielDoberer1,eral.Equilibriumofacidifyingandalkalinizingmetabolicacid–basedisordersincirrhosis.LiverInternational2005:25:505–512310×(ascites:0ifabsentormedicallycontrolledand1ifuncontrolled)+0.肝酶升高程度与肝细胞损伤程度成正相关（限于急性肝损伤）Jan27;89(2):222-6.Cardiopulmonarycomplicationsinchronicliverdisease.SevereIntraoperativeHyperglycemiaIsIndependentlyAssociatedWithSurgicalSiteInfectionAfterLiverTransplantation.Papadakosa,BurkhardLachmannCurrentOpinioninAnaesthesiology,23:133–138ClinChem2000;46(12):2027-49.Earlylactateclearanceisassociatedwithimprovedoutcomeinseveresepsisandsepticshock.肝功能损害与Sepsis管向东文档pptAACNAdvancedCriticalCare;21:2,165–184WorldJGastroenterol2006January28;12(4):526-538（五）糖代谢高血糖：胰岛素耐受（与肝脏疾病严重程度相关）低血糖：肝脏利用糖原障碍，糖酵解受损AparajitaDey,KarthikeyanChandrasekaran.HyperglycemiaInducedChangesinLiver:InvivoandInvitroStudies.CurrentDiabetesReviews,,5,67-78Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology,26:214–221肝功能状态的判断糖代谢：严重高血糖与手术部位(Surgicalsiteinfection)感染密切相关高血糖增加术后移植物排斥风险ChulsooPark,ChehaoHsu,etal.SevereIntraoperativeHyperglycemiaIsIndependentlyAssociatedWithSurgicalSiteInfectionAfterLiverTransplantation.Transplantation;87:1031–1036WalliaA,ParikhND,MolitchME.Posttransplanthyperglycemiaisassociatedwithincreasedriskofliverallograftrejection.Transplantation.Jan27;89(2):222-6.（六）肝酶学DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.分类标志物部位肝细胞完整性AST肝、心、骨骼肌、肾、脑、红细胞ALT肝胆汁淤滞碱性磷酸酶骨骼、小肠、肝、胎盘谷氨酰转移酶与碱性磷酸酶水平相关（六）肝酶学DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.肝酶学肝酶升高程度与肝细胞损伤程度成正相关（限于急性肝损伤）慢性肝损伤、肝癌和肝衰竭患者的转氨酶不能真实反映其肝脏损害的程度。（滞后性）EdoardoG.Giannini,RobertoTesta,VincenzoSavarino.CMAJ2005;172(3):367-79DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.蛋白质蛋白质代谢：血清总蛋白：90%在肝脏合成白蛋白：全部在肝脏合成急性肝损害、局灶性肝损害:二者多正常〔肝代偿能力强、清蛋白半衰期长(17-21天）〕延迟性肝损害:二者均下降（反映肝实质细胞储备功能）血氨血氨AlisonS.Clay,BryanE.Hainline.HyperammonemiaintheICU.CHEST2007;132:1368–1378（七）序贯脏器损伤肾脏功能障碍呼吸功能障碍血流动力学异常感染AnneM.Larson.Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology,26:214–221.1、肝肾综合征－发病机制AndresCardenas.HepatorenalSyndrome:ADreadedComplicationofEnd-StageLiverDisease.AmJGastroenterol2005;100:460-467肝肾综合征－实验室检查ElaineM.Fisher,DianeK.Brown.HepatorenalSyndrome.AACNAdvancedCriticalCare;21:2,165–1842、肝肺综合征－发病机制RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed;358:2378-87.Normalalveolarventilationandpulmonarybloodflow肝肺综合征－发病机制毛细血管扩张通气/血流失调肺内分流RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed;358:2378-87.肝肺综合征诊断参考alveolar–arterialoxygengradientliverdiseaseand/orportalhypertensionintrapulmonaryvasculardilatationUlfHempricha,PeterJ.Papadakosa,BurkhardLachmannCurrentOpinioninAnaesthesiology,23:133–1383、血流动力学改变－发病机制血管舒张因子释放SørenMøller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538血流动力学改变－循环系统表现SørenMøller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-5384、感染免疫功能受损感染风险增加病原菌：细菌，真菌，合并感染感染部位：肺47%，血26%，尿23%AnneM.Larson.CurrentOpinioninGastroenterology,26:214–221JavierVaquero,JuliePolson,etal.InfectionandtheProgressionofHepaticEncephalopathyinAcuteLiverFailure.Gastroenterology2003;125:755–7644.其他判断方法代谢呼吸试验影像学检查代谢呼吸试验13C-phenylalaninebreathtests-苯丙氨酸羟化酶活性13C-galactosebreathtests-半乳糖激酶活性上述两种可判断肝硬化程度并与Child–Turcotte–Pugh评分密切相关13C-methioninebreathtest-肝脏线粒体氧化功能13C-caffeinebreathtest-HBV相关性纤维变性以及长期拉米夫定治疗后肝功能的改善13C-methacetinbreathtest-急\慢性肝脏损害Y.ILAN.Reviewarticle:theassessmentofliverfunctionusingbreathTests.AlimentPharmacolTher2007:26,1293–1302影像学检查B超、CT、MR核素：HepatobiliaryScintigraphy－评估术后肝衰，尤肝实质剩余量不明时99MTc-GSAScintigraphy－术前肝脏储备，术后肝脏再生其它：1HNMRspectroscopicstudy－移植术后肝功能评估WilmardeGraaf,RoelofJ.Bennink,etal.JNuclMed;51:742–752WilmardeGraaf,KrijnP.vanLienden,etal.JGastrointestSurg;14:369–378PratimaTripathi,LakshmiBala,etal.JGastrointestinLiverDisSeptember;18;3,329-336,SørenMøller,JensHHenriksen.慢性肝损伤、肝癌和肝衰竭患者的转氨酶不能真实反映其肝脏损害的程度。免疫功能受损感染风险增加AlimentPharmacolTher2007:26,1293–13022007Jul;28(1):35-8Theriskscoresforindividualpatientswerecalculatedusingthefollowingequation:支链氨基酸和假神经递质学说InfectionandtheProgressionofHepaticEncephalopathyinAcuteLiverFailure.Posttransplanthyperglycemiaisassociatedwithincreasedriskofliverallograftrejection.MedClinNAm93()931–950Lacticacidosis.LiverTranspl13:822-828,2007.InfectionandtheProgressionofHepaticEncephalopathyinAcuteLiverFailure.MarcelLevi,StevenMOpal.