严重肝病引起的以代谢紊乱为基础的神经福建肝病医院课件

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1、HepticEcephlopahy福州白湖亭医院肝病科Definition(1)Hepaticencephalopathy(HE)Itrepresentsareversibledecreaseinneurologicalfunction,baseduponthedisorderofmetabolismwhichiscausedbyseveredecompensatedliverdisease.严重肝病引起的以代谢紊乱为基础的神经、精神综合征。主要临床表现为意识障碍、行为失常和昏迷Definition(2)SubclinicalorlatentHEdiagnosedonlyby

2、precisementaltestsorEEG,noobviousclinicalandbiochemicalabnormalitiesIncidence/prevalenceUniversalfeatureofacuteliverfailure50%~70%inchronichepaticfailureDifficulttoestimateEtiologyFulminanthepaticfailureacutesevereviralhepatitis,drug/toxin,acutefattyliverofpregnancyDuetoacutehepatocellularn

3、ecrosisChronicliverdiseasecirrhosisofalltypes,surgicallyinducedportal-systemicshunts,primarylivercancerDuetooneormorepotentiallyreversibleprecipitatingfactorsPathogenesis(1)ToxicmaterialsderivedfromnitrogeneoussubstrateinthegutandbypasstheliverHEiscausedbyseveralfactorsactsynergisticallySev

4、eralputativegut-derivedtoxinsidentifiedPathogenesis(2)Postulatedfactors/mechanisms:AmmonnianeurotoxicitySynergisticneurotoxinsExcitatoryinhibitoryneurotransmittersandplasmaaminoacidimbalancehypothesisγ-Aminobutyricacid（GABA）/BZhypothesisAmmonianeurotoxicityOverproductionand/orhypoeccrisisPo

5、orhepato-cellularfunction:incompletemetabolismPortal-systemicencephalopathy:bypassAmmoniaintoxicationInterferewithcerebralmetabolism:Depletionofglutamicacid,asparticacidandATPDepressioncerebralbloodflowandoxygenconsumptionAmmonianeurotoxicityElevationofammonia:detectedin60%~80%Absoluteconce

6、ntrationofammonia,ammoniametabolitesinbloodorcerebrospinalfluids,correlatesonlyroughlywiththepresenceorseverityofHEFewcases:withinnormalrangeSynergisticneurotoxinsAmmoniaMercaptans(硫醇)Short-chainfattyacidsExcitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalanceNeurotransmission:Mediat

7、edbybothexcitatoryandinhibitoryneurotransmittersTheirsynthesiscontrolledbybrainconcentrationoftheprecursoraminoacidsIncreasedaromaticaminoacids(AAAs)Tyrosine（酪氨酸）Phenylalanine（苯丙氨酸）Tryptophan（色氨酸〕DuetothefailureofhepaticdeaminationDecreasedbranched-chain