肝功能損害與sepsis管向東

重癥病人肝臟功能狀態(tài)的判斷管向東精選課件肝臟功能?精選課件肝臟的生理功能精選課件肝臟的生理功能（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精選課件肝臟的生理功能（二）分泌和排泄功能（三）生物轉(zhuǎn)化：解毒作用（四）免疫防御精選課件肝功能狀態(tài)的判斷精選課件HepaticFailureDefinition:Lossoffunctionallivercellmassbelowacriticallevelresultsinliverfailure(acuteorcomplicatingachronicliverdisease)Resultsin:hepaticencephalopathy&Coma,Jaundice,cholestasis,ascites,bleeding,renalfailure,deathAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.精選課件HepaticFailureProductionofEndogenousToxins&DrugmetabolicFailureBileAcids,Bilirubin,Prostacyclins,NO,Toxicfattyacids,Thiols,Indol-phenolmetabolitesThesetoxinscausefurthernecrosis/apoptosisandaviciouscycleDetrimentaltorenal,brainandbonemarrowfunction;resultsinpoorvasculartoneAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.精選課件ICU內(nèi)

如何迅速判斷重癥病人肝臟功能?精選課件（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精選課件腦水腫機(jī)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.精選課件肝性腦病發(fā)病機(jī)制氨中毒學(xué)說GABA/苯二氮卓類受體復(fù)合物學(xué)說支鏈氨基酸和假神經(jīng)遞質(zhì)學(xué)說5-羥色胺學(xué)說鋅/錳學(xué)說W.J.Cash,P.Mcconville,etal.CurrentconceptsintheassessmentandtreatmentofHepaticEncephalopathy.QJMed2010;103:9–16.精選課件其他原因內(nèi)環(huán)境異常------由肝功能異常導(dǎo)致:組織灌注不足：局部/系統(tǒng)血流動力學(xué)異常代謝紊亂：電解質(zhì)/酸堿平衡紊亂精選課件（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精選課件凝血因子減少M(fèi)arcelLevi,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(yán)重缺乏VitK拮抗劑全部凝血因子缺乏精選課件血小板減少M(fèi)arcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222精選課件（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精選課件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.精選課件乳酸&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(guān)（severesepsisandsepticshock）H.BryantNguyen,EmanuelP.Rivers,etal.Earlylactateclearanceisassociatedwithimprovedoutcomeinseveresepsisandsepticshock.CritCareMed2004;32:1637–1642精選課件乳酸&急性肝臟衰竭WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63精選課件乳酸&預(yù)后WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63精選課件乳酸&發(fā)病率、死亡率(肝葉切除術(shù)后)預(yù)測發(fā)病率和死亡率IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8精選課件乳酸與ICU住院時間IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8精選課件（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精選課件（五）糖代謝高血糖：胰島素耐受（與肝臟疾病嚴(yán)重程度相關(guān)）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精選課件肝功能狀態(tài)的判斷糖代謝：嚴(yán)重高血糖與手術(shù)部位(Surgicalsiteinfection)感染密切相關(guān)高血糖增加術(shù)后移植物排斥風(fēng)險ChulsooPark,ChehaoHsu,etal.SevereIntraoperativeHyperglycemiaIsIndependentlyAssociatedWithSurgicalSiteInfectionAfterLiverTransplantation.Transplantation2009;87:1031–1036WalliaA,ParikhND,MolitchME.Posttransplanthyperglycemiaisassociatedwithincreasedriskofliverallograftrejection.Transplantation.2010Jan27;89(2):222-6.精選課件（六）肝酶學(xué)DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.精選課件分類標(biāo)志物部位肝細(xì)胞完整性AST肝、心、骨骼肌、腎、腦、紅細(xì)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(guān)（六）肝酶學(xué)DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.精選課件肝酶學(xué)肝酶升高程度與肝細(xì)胞損傷程度成正相關(guān)（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(shí)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.精選課件蛋白質(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:二者多正常〔肝代償能力強(qiáng)、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(shí)質(zhì)細(xì)胞儲備功能）精選課件血氨血氨AlisonS.Clay,BryanE.Hainline.HyperammonemiaintheICU.CHEST2007;132:1368–1378精選課件（七）序貫臟器損傷腎臟功能障礙呼吸功能障礙血流動力學(xué)異常感染AnneM.Larson.Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology2010,26:214–221.精選課件1、肝腎綜合征－發(fā)病機(jī)制AndresCardenas.HepatorenalSyndrome:ADreadedComplicationofEnd-StageLiverDisease.AmJGastroenterol2005;100:460-467精選課件肝腎綜合征－實(shí)驗(yàn)室檢查ElaineM.Fisher,DianeK.Brown.HepatorenalSyndrome.AACNAdvancedCriticalCare2010;21:2,165–184精選課件2、肝肺綜合征－發(fā)病機(jī)制RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed2008;358:2378-87.Normalalveolarventilationandpulmonarybloodflow精選課件肝肺綜合征－發(fā)病機(jī)制毛細(xì)血管擴(kuò)張通氣/血流失調(diào)肺內(nèi)分流RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed2008;358:2378-87.精選課件肝肺綜合征診斷參考alveolar–arterialoxygengradientliverdiseaseand/orportalhypertensionintrapulmonaryvasculardilatationUlfHempricha,PeterJ.Papadakosa,BurkhardLachmannCurrentOpinioninAnaesthesiology2010,23:133–138精選課件3、血流動力學(xué)改變－發(fā)病機(jī)制血管舒張因子釋放S?renM?ller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538精選課件血流動力學(xué)改變－循環(huán)系統(tǒng)表現(xiàn)S?renM?ller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538精選課件4、感染免疫功能受損感染風(fēng)險增加病原菌：細(xì)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精選課件4.其他判斷方法代謝呼吸試驗(yàn)影像學(xué)檢查精選課件代謝呼吸試驗(yàn)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(guān)13C-methioninebreathtest-肝臟線粒體氧化功能13C-caffeinebreathtest-HBV相關(guān)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精選課件影像學(xué)檢查B超、CT、MR核素：HepatobiliaryScintigraphy－評估術(shù)后肝衰，尤肝實(shí)質(zhì)剩余量不明時99MTc-GSAScintigraphy－術(shù)前肝臟儲備，術(shù)后肝臟再生其它：1HNMRspectroscopicstudy－移植術(shù)后肝功能評估WilmardeGraaf,RoelofJ.Bennink,etal.JNuclMed2010;51:742–752WilmardeGraaf,KrijnP.vanLienden,etal.JGastrointestSurg2010;14:369–378PratimaTripathi,LakshmiBala,etal.JGastrointestinLiverDisSeptember2009;18;3,329-336,精選課件評分系統(tǒng)Child-Pugh-TurcotteMELDBioCliMscore精選課件（一）評分系統(tǒng)-CTPJuanF.Gallegos-Orozco,HugoE.Vargas.LiverTransplantation:FromChildtoMELD.MedClinNAm93(2009)931–950精選課件（二）評分系統(tǒng)-MELD精選課件評分系統(tǒng)-MELDShahidM.Mal