肝功能損害與Sepsis管向東

重癥病人肝臟功能狀態(tài)的判斷管向東當(dāng)前第1頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝臟功能?當(dāng)前第2頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝臟的生理功能當(dāng)前第3頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(dāng)前第4頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(dāng)前第5頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝功能狀態(tài)的判斷當(dāng)前第6頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)HepaticFailureDefinition:Lossoffunctionallivercellmassbelowacriticallevelresultsinliverfailure(acuteorcomplicatingachronicliverdisease)Resultsin:hepaticencephalopathy&Coma,Jaundice,cholestasis,ascites,bleeding,renalfailure,deathAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.當(dāng)前第7頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)HepaticFailureProductionofEndogenousToxins&DrugmetabolicFailureBileAcids,Bilirubin,Prostacyclins,NO,Toxicfattyacids,Thiols,Indol-phenolmetabolitesThesetoxinscausefurthernecrosis/apoptosisandaviciouscycleDetrimentaltorenal,brainandbonemarrowfunction;resultsinpoorvasculartoneAndresT.Blei.PathophysiologyofBrainEdemainFulminantHepaticFailure,Revisited.MetabolicBrainDisease,2001;16:Nos.1/2.當(dāng)前第8頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)ICU內(nèi)

如何迅速判斷重癥病人肝臟功能?當(dāng)前第9頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（一）意識(shí)狀態(tài)清醒？譫妄？昏睡、昏迷？原因：肝性腦病腦水腫其他當(dāng)前第10頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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.當(dāng)前第11頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝性腦病發(fā)病機(jī)制氨中毒學(xué)說(shuō)GABA/苯二氮卓類受體復(fù)合物學(xué)說(shuō)支鏈氨基酸和假神經(jīng)遞質(zhì)學(xué)說(shuō)5-羥色胺學(xué)說(shuō)鋅/錳學(xué)說(shuō)W.J.Cash,P.Mcconville,etal.CurrentconceptsintheassessmentandtreatmentofHepaticEncephalopathy.QJMed2010;103:9–16.當(dāng)前第12頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(dòng)力學(xué)異常代謝紊亂：電解質(zhì)/酸堿平衡紊亂當(dāng)前第13頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（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(dāng)前第14頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)凝血因子減少M(fèi)arcelLevi,StevenMOpal.CriticalCare2006,10:222TESTRESULTSCAUSEPT延長(zhǎng)，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(zhǎng)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(zhǎng)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當(dāng)前第15頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)血小板減少M(fèi)arcelLevi,StevenMOpal.Coagulationabnormalitiesincriticallyillpatients.CriticalCare2006,10:222當(dāng)前第16頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（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(dāng)前第17頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(dāng)前第18頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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當(dāng)前第19頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)乳酸&急性肝臟衰竭WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63當(dāng)前第20頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)乳酸&預(yù)后WilliamBernal,NoraDonaldson,etal.Bloodlactateasanearlypredictorofoutcomeinparacetamolinducedacuteliverfailure:acohortstudy.Lancet2002;359:558–63當(dāng)前第21頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)乳酸&發(fā)病率、死亡率(肝葉切除術(shù)后)預(yù)測(cè)發(fā)病率和死亡率IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8當(dāng)前第22頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)乳酸與ICU住院時(shí)間IzuruWatanabe,ToshihikoMayumi,etal.Hyperlactemiacanpredicttheprognosisofliverresection.Shock.2007Jul;28(1):35-8當(dāng)前第23頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（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(dāng)前第24頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（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當(dāng)前第25頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(xiǎn)ChulsooPark,ChehaoHsu,etal.SevereIntraoperativeHyperglycemiaIsIndependentlyAssociatedWithSurgicalSiteInfectionAfterLiverTransplantation.Transplantation2009;87:1031–1036WalliaA,ParikhND,MolitchME.Posttransplanthyperglycemiaisassociatedwithincreasedriskofliverallograftrejection.Transplantation.2010Jan27;89(2):222-6.當(dāng)前第26頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（六）肝酶學(xué)DufourDR,LottJA,etal.ClinChem2000;46(12):2027-49.當(dāng)前第27頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(pán)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.當(dāng)前第28頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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.當(dāng)前第29頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(zhǎng)(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(chǔ)備功能）當(dāng)前第30頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)血氨血氨AlisonS.Clay,BryanE.Hainline.HyperammonemiaintheICU.CHEST2007;132:1368–1378當(dāng)前第31頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（七）序貫臟器損傷腎臟功能障礙呼吸功能障礙血流動(dòng)力學(xué)異常感染AnneM.Larson.Diagnosisandmanagementofacuteliverfailure.CurrentOpinioninGastroenterology2010,26:214–221.當(dāng)前第32頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)1、肝腎綜合征－發(fā)病機(jī)制AndresCardenas.HepatorenalSyndrome:ADreadedComplicationofEnd-StageLiverDisease.AmJGastroenterol2005;100:460-467當(dāng)前第33頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝腎綜合征－實(shí)驗(yàn)室檢查ElaineM.Fisher,DianeK.Brown.HepatorenalSyndrome.AACNAdvancedCriticalCare2010;21:2,165–184當(dāng)前第34頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)2、肝肺綜合征－發(fā)病機(jī)制RobertoRodríguez-Roisin,MichaelJ.Krowka.HepatopulmonarySyndrome—ALiver-InducedLungVascularDisorder.NEnglJMed2008;358:2378-87.Normalalveolarventilationandpulmonarybloodflow當(dāng)前第35頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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.當(dāng)前第36頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)肝肺綜合征診斷參考alveolar–arterialoxygengradientliverdiseaseand/orportalhypertensionintrapulmonaryvasculardilatationUlfHempricha,PeterJ.Papadakosa,BurkhardLachmannCurrentOpinioninAnaesthesiology2010,23:133–138當(dāng)前第37頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)3、血流動(dòng)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當(dāng)前第38頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)血流動(dòng)力學(xué)改變－循環(huán)系統(tǒng)表現(xiàn)S?renM?ller,JensHHenriksen.Cardiopulmonarycomplicationsinchronicliverdisease.WorldJGastroenterol2006January28;12(4):526-538當(dāng)前第39頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)4、感染免疫功能受損感染風(fēng)險(xiǎn)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當(dāng)前第40頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)4.其他判斷方法代謝呼吸試驗(yàn)影像學(xué)檢查當(dāng)前第41頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)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(píng)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(zhǎng)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當(dāng)前第42頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)影像學(xué)檢查B超、CT、MR核素：HepatobiliaryScintigraphy－評(píng)估術(shù)后肝衰，尤肝實(shí)質(zhì)剩余量不明時(shí)99MTc-GSAScintigraphy－術(shù)前肝臟儲(chǔ)備，術(shù)后肝臟再生其它：1HNMRspectroscopicstudy－移植術(shù)后肝功能評(píng)估WilmardeGraaf,RoelofJ.Bennink,etal.JNuclMed2010;51:742–752WilmardeGraaf,KrijnP.vanLienden,etal.JGastrointestSurg2010;14:369–378PratimaTripathi,LakshmiBala,etal.JGastrointestinLiverDisSeptember2009;18;3,329-336,當(dāng)前第43頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)評(píng)分系統(tǒng)Child-Pugh-TurcotteMELDBioCliMscore當(dāng)前第44頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（一）評(píng)分系統(tǒng)-CTPJuanF.Gallegos-Orozco,HugoE.Vargas.LiverTransplantation:FromChildtoMELD.MedClinNAm93(2009)931–950當(dāng)前第45頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)（二）評(píng)分系統(tǒng)-MELD當(dāng)前第46頁(yè)\共有52頁(yè)\編于星期一\13點(diǎn)評(píng)分系統(tǒng)-MELDShahidM.Malik,JawadAhmad