肝功能損害與管向東演示文稿當前1頁，總共47頁。（優(yōu)選）肝功能損害與管向東當前2頁，總共47頁。肝臟的生理功能當前3頁，總共47頁。肝臟的生理功能（一）代謝功能糖類：肝糖原貯存、分解、糖異生脂類：脂肪、膽固醇及磷脂蛋白質(zhì)：血清總蛋白、白蛋白血漿凝血因子幾乎全部在肝臟合成當前4頁，總共47頁。肝臟的生理功能（二）分泌和排泄功能（三）生物轉(zhuǎn)化：解毒作用（四）免疫防御當前5頁，總共47頁。肝功能狀態(tài)的判斷當前6頁，總共47頁。HepaticFailureDefinition:Lossoffunctionallivercellmassbelowacriticallevelresultsinliverfailure(acuteorcomplicatingachronicliverdisease)Resultsin:hepaticencephalopathy&Coma,Jaundice,cholestasis,ascites,bleeding,renalfailure,deathAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.當前7頁，總共47頁。HepaticFailureProductionofEndogenousToxins&DrugmetabolicFailureBileAcids,Bilirubin,Prostacyclins,NO,Toxicfattyacids,Thiols,Indol-phenolmetabolitesThesetoxinscausefurthernecrosis/apoptosisandaviciouscycleDetrimentaltorenal,brainandbonemarrowfunction;resultsinpoorvasculartoneAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.當前8頁，總共47頁。ICU內(nèi)

如何迅速判斷重癥病人肝臟功能?當前9頁，總共47頁。（一）意識狀態(tài)清醒？譫妄？昏睡、昏迷？原因：肝性腦病腦水腫其他當前10頁，總共47頁。腦水腫機制滲透性異常血氨、谷氨酰胺腦血流減慢血管舒張、腦代謝減慢AndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.當前11頁，總共47頁。肝性腦病發(fā)病機制氨中毒學說GABA/苯二氮卓類受體復合物學說支鏈氨基酸和假神經(jīng)遞質(zhì)學說5-羥色胺學說鋅/錳學說W.J.Cash,P.Mcconville,etal.CurrentconceptsintheassessmentandtreatmentofHepaticEncephalopathy.QJMed2010;103:9–16.當前12頁，總共47頁。其他原因內(nèi)環(huán)境異常------由肝功能異常導致:組織灌注不足：局部/系統(tǒng)血流動力學異常代謝紊亂：電解質(zhì)/酸堿平衡紊亂當前13頁，總共47頁。（二）凝血功能障礙凝血因子產(chǎn)生減少血漿凝血因子幾乎全部在肝臟合成MarcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222當前14頁，總共47頁。凝血因子減少MarcelLevi,StevenMOpal.CriticalCare2006,10:222TESTRESULTSCAUSEPT延長，APTT正常VII因子缺乏輕度VitK缺乏少量VitK拮抗劑PT正常，APTT延長VII、IX、XI因子缺乏使用非小分子肝素抑制劑抗體和/或抗磷脂抗體XII因子和前激肽釋放酶缺乏PT、APTT均延長X、V、II因子缺乏VitK嚴重缺乏VitK拮抗劑全部凝血因子缺乏當前15頁，總共47頁。血小板減少MarcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222當前16頁，總共47頁。（三）乳酸主要在肝臟代謝（>90%）糖酵解產(chǎn)物NicolaosF.Madias.Lacticacidosis.KidneyInternational,Vol.29(1986),752-774.DanielDeBacker.Lacticacidosis.IntensiveCareMed(2003)29:699–702當前17頁，總共47頁。乳酸水平升高的原因氧需求增加組織缺氧肝衰竭藥物毒物特殊疾病:糖尿病NicolaosF.Madias.Lacticacidosis.KidneyInternational,Vol.29(1986),752-774.當前18頁，總共47頁。乳酸&膿毒癥乳酸清除率—早期提示組織缺氧程度并與死亡率相關（severesepsisandsepticshock）H.BryantNguyen,EmanuelP.Rivers,etal.Earlylactateclearanceisassociatedwithimprovedoutcomeinseveresepsisandsepticshock.CritCareMed2004;32:1637–1642當前19頁，總共47頁。乳酸&急性肝臟衰竭WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63當前20頁，總共47頁。乳酸&預后WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63當前21頁，總共47頁。乳酸&發(fā)病率、死亡率(肝葉切除術后)預測發(fā)病率和死亡率IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8當前22頁，總共47頁。乳酸與ICU住院時間IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8當前23頁，總共47頁。（四）酸堿平衡酸中毒:

乳酸堿中毒:

低白蛋白血癥（堿化血漿）Georg-ChristianFunk,DanielDoberer1,eral.Equilibriumofacidifyingandalkalinizingmetabolicacid–basedisordersincirrhosis.LiverInternational2005:25:505–512當前24頁，總共47頁。（五）糖代謝高血糖：胰島素耐受（與肝臟疾病嚴重程度相關）低血糖：肝臟利用糖原障礙，糖酵解受損AparajitaDey,KarthikeyanChandrasekaran.HyperglycemiaInducedChangesinLiver:InvivoandInvitroStudies.CurrentDiabetesReviews,2009,5,67-78Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology2010,26:214–221當前25頁，總共47頁。肝功能狀態(tài)的判斷糖代謝：嚴重高血糖與手術部位(Surgicalsiteinfection)感染密切相關高血糖增加術后移植物排斥風險ChulsooPark,ChehaoHsu,etal.SevereIntraoperativeHyperglycemiaIsIndependentlyAssociatedWithSurgicalSiteInfectionAfterLiverTransplantation.Transplantation2009;87:1031–1036WalliaA,ParikhND,MolitchME.Posttransplanthyperglycemiaisassociatedwithincreasedriskofliverallograftrejection.Transplantation.2010Jan27;89(2):222-6.當前26頁，總共47頁。（六）肝酶學DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.當前27頁，總共47頁。分類標志物部位肝細胞完整性AST肝、心、骨骼肌、腎、腦、紅細胞ALT肝膽汁淤滯堿性磷酸酶骨骼、小腸、肝、胎盤谷氨酰轉(zhuǎn)移酶與堿性磷酸酶水平相關（六）肝酶學DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.當前28頁，總共47頁。肝酶學肝酶升高程度與肝細胞損傷程度成正相關（限于急性肝損傷）慢性肝損傷、肝癌和肝衰竭患者的轉(zhuǎn)氨酶不能真實反映其肝臟損害的程度。（滯后性）EdoardoG.Giannini,RobertoTesta,VincenzoSavarino.CMAJ2005;172(3):367-79DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.當前29頁，總共47頁。蛋白質(zhì)蛋白質(zhì)代謝：血清總蛋白：90%在肝臟合成白蛋白：全部在肝臟合成急性肝損害、局灶性肝損害:二者多正?！哺未鷥斈芰?、清蛋白半衰期長(17-21天）〕延遲性肝損害:二者均下降（反映肝實質(zhì)細胞儲備功能）當前30頁，總共47頁。血氨血氨AlisonS.Clay,BryanE.Hainline.HyperammonemiaintheICU.CHEST2007;132:1368–1378當前31頁，總共47頁。（七）序貫臟器損傷腎臟功能障礙呼吸功能障礙血流動力學異常感染AnneM.Larson.Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology2010,26:214–221.當前32頁，總共47頁。1、肝腎綜合征－發(fā)病機制AndresCardenas.HepatorenalSyndrome:ADreadedComplicationofEnd-StageLiverDisease.AmJGastroenterol2005;100:460-467當前33頁，總共47頁。肝腎綜合征－實驗室檢查ElaineM.Fisher,DianeK.Brown.HepatorenalSyndrome.AACNAdvancedCriticalCare2010;21:2,165–184當前34頁，總共47頁。2、肝肺綜合征－發(fā)病機制RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed2008;358:2378-87.Normalalveolarventilationandpulmonarybloodflow當前35頁，總共47頁。肝肺綜合征－發(fā)病機制毛細血管擴張通氣/血流失調(diào)肺內(nèi)分流RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed2008;358:2378-87.當前36頁，總共47頁。肝肺綜合征診斷參考alveolar–arterialoxygengradientliverdiseaseand/orportalhypertensionintrapulmonaryvasculardilatationUlfHempricha,PeterJ.Papadakosa,BurkhardLachmannCurrentOpinioninAnaesthesiology2010,23:133–138當前37頁，總共47頁。3、血流動力學改變－發(fā)病機制血管舒張因子釋放S?renM?ller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538當前38頁，總共47頁。血流動力學改變－循環(huán)系統(tǒng)表現(xiàn)S?renM?ller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538當前39頁，總共47頁。4、感染免疫功能受損感染風險增加病原菌：細菌，真菌，合并感染感染部位：肺47%，血26%，尿23%AnneM.Larson.CurrentOpinioninGastroenterology2010,26:214–221JavierVaquero,JuliePolson,etal.InfectionandtheProgressionofHepaticEncephalopathyinAcuteLiverFailure.Gastroenterology2003;125:755–764當前40頁，總共47頁。4.其他判斷方法代謝呼吸試驗影像學檢查當前41頁，總共47頁。代謝呼吸試驗13C-phenylalaninebreathtests-苯丙氨酸羥化酶活性13C-galactosebreathtests-半乳糖激酶活性上述兩種可判斷肝硬化程度并與Child–Turcotte–Pugh評分密切相關13C-methioninebreathtest-肝臟線粒體氧化功能13C-caffeinebreathtest-HBV相關性纖維變性以及長期拉米夫定治療后肝功能的改善13C-methacetinbreathtest-急\慢性肝臟損害Y.ILAN.Reviewarticle:theassessmentofliverfunctionusingbreathTests.AlimentPharmacolTher2007:26,1293–1302