急性肝功能衰竭診治課件

急性肝功能衰竭1急性肝功能衰竭1急性肝功能衰竭的定義Acuteliverfailure(ALF)isdefinedaslife-threateningliverinjuryintheabsenceofpreexistingliverdiseasewithcoagulopathy(prothrombintime>15secondsorinternationalnormalizedratio[INR]1.5)andhepaticencephalopathy(HE)thatdevelopswithin26weeksofinitialsymptomsTheterm‘‘fulminanthepaticfailure’’(FHF)isusedwhenHEdevelopswithin8weeksofjaundice2急性肝功能衰竭的定義AcuteliverfailureEtiologyofacuteliverfailure3Etiologyofacuteliverfailur44肝性腦病的分期臨床上按神經(jīng)精神癥狀的輕重把肝性腦病分為四期：一期(前驅(qū)期):輕微的神經(jīng)精神癥狀,可表現(xiàn)出欣快、反應(yīng)遲鈍、睡眠節(jié)律的變化。二期(昏迷前期):一期癥狀加重,可出現(xiàn):行為異常、嗜睡、精神錯(cuò)亂.經(jīng)常出現(xiàn)撲翼樣震顫等.三期(昏睡期):有明顯的精神錯(cuò)亂、昏睡、肌張力↑等癥狀.四期(昏迷期):神志喪失,不能喚醒,沒有撲翼樣震顫等.5肝性腦病的分期臨床上按神經(jīng)精神癥狀的輕重把肝性腦病分為四期：肝性腦病分期6肝性腦病分期6肝性腦病發(fā)病機(jī)制

氨中毒學(xué)說假性神經(jīng)遞質(zhì)學(xué)說血漿氨基酸失衡學(xué)說

GABA學(xué)說其他神經(jīng)毒質(zhì)在肝性腦病發(fā)病中的作用7肝性腦病發(fā)病機(jī)制氨中毒學(xué)說7氨中毒(ammoniaintoxication)學(xué)說血氨增高的原因：氨清除不足（主要）圖肝臟合成尿素的鳥氨酸循環(huán)

OCT：鳥氨酸氨基甲酰轉(zhuǎn)移酶

CPS：氨基甲酰磷酸合成酶氨的清除：8氨中毒(ammoniaintoxication)學(xué)說血氨增proteinNH3NH3ureaNormalmetabolism9proteinNH3NH3ureaNormal9Liverfailure肝衰竭proteinNH3NH3urea×BloodNH3↑10LiverfailureproteinNH3NH3ureaLiverfailure肝衰竭proteinNH3NH3urea×血NH3↑ShuntingCirculation門-體分流↑11LiverfailureproteinNH3NH3ureaCerebralEdemaandIntracranialHypertensionHepaticencephalopathyammoniainflammationalteredneurotransmissionpathwayscerebralhemodynamicdysautoregulation12CerebralEdemaandIntracraniaCerebralEdemaandIntracranialHypertensionOthercommontriggersforICPelevation:volumeoverloadhyponatremiaseverehypercarbiasevereacidosisincreasedthoracicandabdominalcompartmentpressures13CerebralEdemaandIntracraniaNeuromonitoringstrategiesInvasiveneuromonitoringstrategiesNoninvasiveneuromonitoringstrategiesserialheadcomputedtomography(CT)transcranialDopplerjugularbulboximetrypupillometry14NeuromonitoringstrategiesInvaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00015AlgorithmforthediagnosticaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00016AlgorithmforthediagnosticaAnnualUpdateinIntensiveCareandEmergencyMedicine201517AnnualUpdateinIntensiveCarIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00018IntensivecaresupportivestraIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00019IntensivecaresupportivestraAKIinALFAcuterenalfailuredevelopsin55–68%ofallpatientswhopresentwithALFandinthevastmajorityofcasesreverseswithresolutionofliverinjuryorwithtransplantationmechanismdirectrenaltoxicityfunctionalimpairmentasseeninthehepatorenalsyndromeMooreK.Renalfailureinacuteliverfailure.EurJGastroenterolHepatol1999;11:967–975.LeitheadJA,FergusonJW,BatesCM,etal.Thesystemicinflammatoryresponsesyndromeispredictiveofrenaldysfunctioninpatientswithnonparacetamol-inducedacuteliverfailure.Gut2009;58:443–449.20AKIinALFAcuterenalfailure2121臨床問題該患者無明顯活動(dòng)性出血征象，監(jiān)測凝血功能：INR3.2，APTT65s，F(xiàn)IB1.2g/L，PLT40109/L需要輸注血制品（血漿、冷沉淀、血小板）以糾正凝血功能障礙？22臨床問題該患者無明顯活動(dòng)性出血征象，監(jiān)測凝血功能：INR3ProthrombinTime,PT23ProthrombinTime,PT232424252526262727凝血功能再平衡健康人VS肝功能不全28凝血功能再平衡健康人VSPeripheral-VeinThrombosisArterialThrombosisPortal-VeinThrombosis：等待肝移植的患者中發(fā)生率8-25%FrancozC,BelghitiJ,VilgrainV,etal.Splanchnicveinthrombosisincandidatesforlivertransplantation:usefulnessofscreeningandanticoagulation.Gut2005;54:691-7.29Peripheral-VeinThrombosisFranHematologicalSupportHb>7.0g/dlINR<6Plateletcount>20109/LFibrinogen>1.0g/lAnnualUpdateinIntensiveCareandEmergencyMedicine201530HematologicalSupportHb>7.0臨床問題對于肝功能衰竭需要進(jìn)行CRRT的患者，監(jiān)測其凝血功能顯著異常（APTT、INR顯著升高），怎樣開展CRRT治療？無抗凝？枸櫞酸抗凝？31臨床問題對于肝功能衰竭需要進(jìn)行CRRT的患者，監(jiān)測其凝血功能該試驗(yàn)共納入71例患者，共更換539次濾器管路。平均的濾器壽命為9(6–16)小時(shí)。其中51例患者接受完全無抗凝CRRT，其濾器壽命為12(7-24)小時(shí)。余下20例患者開始也行無抗凝CRRT，其濾器壽命為7(5-11)小時(shí)，但其后即使予以全身肝素抗凝或局部肝素抗凝使得APTT顯著延長，也并不增加其濾器的壽命32該試驗(yàn)共納入71例患者，共更換539次濾器管路。平均的濾器壽所有43個(gè)濾器壽命均超過24小時(shí)，其中32個(gè)(74%)的濾器壽命達(dá)到72小時(shí)在提前更換濾器的事件中，只有3例是因?yàn)榭傗}/游離鈣>2.5盡管在嚴(yán)重肝功能衰竭患者中進(jìn)行局部枸櫞酸抗凝的CVVHD治療會(huì)造成體內(nèi)枸櫞酸蓄積，但并沒有造成酸堿平衡紊亂及電解質(zhì)紊亂在嚴(yán)重肝功能衰竭患者中進(jìn)行局部枸櫞酸抗凝的血液凈化治療是安全、可行的，但仍有必要密切監(jiān)測總鈣/游離鈣以保障患者安全33所有43個(gè)濾器壽命均超過24小時(shí)，其中32個(gè)(74%)的濾器目的：研究心臟術(shù)后并發(fā)肝、腎功能不全患者進(jìn)行局部枸櫞酸抗凝的CRRT治療的安全性及有效性結(jié)果：共納入15例心臟外科術(shù)后并發(fā)肝、腎功能不全患者，在治療過程中肝酶（AST、ALT）、膽紅素、r-GT均沒有顯著改變。濾器后游離鈣、患者體內(nèi)游離鈣及患者體內(nèi)總鈣/游離鈣水平均穩(wěn)定，未發(fā)現(xiàn)枸櫞酸中毒結(jié)論：在急性肝功能衰竭患者中進(jìn)行局部枸櫞酸抗凝是有效、安全的34目的：研究心臟術(shù)后并發(fā)肝、腎功能不全患者進(jìn)行局部枸櫞酸抗凝的急性肝功能衰竭35急性肝功能衰竭1急性肝功能衰竭的定義Acuteliverfailure(ALF)isdefinedaslife-threateningliverinjuryintheabsenceofpreexistingliverdiseasewithcoagulopathy(prothrombintime>15secondsorinternationalnormalizedratio[INR]1.5)andhepaticencephalopathy(HE)thatdevelopswithin26weeksofinitialsymptomsTheterm‘‘fulminanthepaticfailure’’(FHF)isusedwhenHEdevelopswithin8weeksofjaundice36急性肝功能衰竭的定義AcuteliverfailureEtiologyofacuteliverfailure37Etiologyofacuteliverfailur384肝性腦病的分期臨床上按神經(jīng)精神癥狀的輕重把肝性腦病分為四期：一期(前驅(qū)期):輕微的神經(jīng)精神癥狀,可表現(xiàn)出欣快、反應(yīng)遲鈍、睡眠節(jié)律的變化。二期(昏迷前期):一期癥狀加重,可出現(xiàn):行為異常、嗜睡、精神錯(cuò)亂.經(jīng)常出現(xiàn)撲翼樣震顫等.三期(昏睡期):有明顯的精神錯(cuò)亂、昏睡、肌張力↑等癥狀.四期(昏迷期):神志喪失,不能喚醒,沒有撲翼樣震顫等.39肝性腦病的分期臨床上按神經(jīng)精神癥狀的輕重把肝性腦病分為四期：肝性腦病分期40肝性腦病分期6肝性腦病發(fā)病機(jī)制

氨中毒學(xué)說假性神經(jīng)遞質(zhì)學(xué)說血漿氨基酸失衡學(xué)說

GABA學(xué)說其他神經(jīng)毒質(zhì)在肝性腦病發(fā)病中的作用41肝性腦病發(fā)病機(jī)制氨中毒學(xué)說7氨中毒(ammoniaintoxication)學(xué)說血氨增高的原因：氨清除不足（主要）圖肝臟合成尿素的鳥氨酸循環(huán)

OCT：鳥氨酸氨基甲酰轉(zhuǎn)移酶

CPS：氨基甲酰磷酸合成酶氨的清除：42氨中毒(ammoniaintoxication)學(xué)說血氨增proteinNH3NH3ureaNormalmetabolism43proteinNH3NH3ureaNormal9Liverfailure肝衰竭proteinNH3NH3urea×BloodNH3↑44LiverfailureproteinNH3NH3ureaLiverfailure肝衰竭proteinNH3NH3urea×血NH3↑ShuntingCirculation門-體分流↑45LiverfailureproteinNH3NH3ureaCerebralEdemaandIntracranialHypertensionHepaticencephalopathyammoniainflammationalteredneurotransmissionpathwayscerebralhemodynamicdysautoregulation46CerebralEdemaandIntracraniaCerebralEdemaandIntracranialHypertensionOthercommontriggersforICPelevation:volumeoverloadhyponatremiaseverehypercarbiasevereacidosisincreasedthoracicandabdominalcompartmentpressures47CerebralEdemaandIntracraniaNeuromonitoringstrategiesInvasiveneuromonitoringstrategiesNoninvasiveneuromonitoringstrategiesserialheadcomputedtomography(CT)transcranialDopplerjugularbulboximetrypupillometry48NeuromonitoringstrategiesInvaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00049AlgorithmforthediagnosticaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00050AlgorithmforthediagnosticaAnnualUpdateinIntensiveCareandEmergencyMedicine201551AnnualUpdateinIntensiveCarIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00052IntensivecaresupportivestraIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00053IntensivecaresupportivestraAKIinALFAcuterenalfailuredevelopsin55–68%ofallpatientswhopresentwithALFandinthevastmajorityofcasesreverseswithresolutionofliverinjuryorwithtransplantationmechanismdirectrenaltoxicityfunctionalimpairmentasseeninthehepatorenalsyndromeMooreK.Renalfailureinacuteliverfailure.EurJGastroenterolHepatol1999;11:967–975.LeitheadJA,FergusonJW,BatesCM,etal.Thesystemicinflammatoryresponsesyndromeispredictiveofrenaldysfunctioninpatientswithnonparacetamol-inducedacuteliverfailure.Gut2009;58:443–449.54AKIinALFAcuterenalfailure5521臨床問題該患者無明顯活動(dòng)性出血征象，監(jiān)測凝血功能：INR3.2，APTT65s，F(xiàn)IB1.2g/L，PLT40109/L需要輸注血制品（血漿、冷沉淀、血小板）以糾正凝血功能障礙？56臨床問題該患者無明顯活動(dòng)性出血征象，監(jiān)測凝血功能：INR3ProthrombinTime,PT57ProthrombinTime,PT235824592560266127凝血功能再平衡健康人VS肝功能不全62凝血功能再平衡健康人VSPeripheral-VeinThrombosisArterialThrombosisPortal-VeinThrombosis：等待肝移植的患者中發(fā)生率8-25%FrancozC,BelghitiJ,VilgrainV,etal.Splanchnicveinthrombosisincandidatesforlivertransplantation:usefulnes