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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HepticEcephlopahy福州白湖亭医院肝病科

1Definition(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

2Definition(2)SubclinicalorlatentHEdiagnosedonlybyprecisementaltestsorEEG,noobviousclinicalandbiochemicalabnormalities

3Incidence/prevalenceUniversalfeatureofacuteliverfailure50%~70%inchronichepaticfailureDifficulttoestimate

4EtiologyFulminanthepaticfailureacutesevereviralhepatitis,drug/toxin,acutefattyliverofpregnancyDuetoacutehepatocellularnecrosisChronicliverdiseasecirrhosisofalltypes,surgicallyinducedportal-systemicshunts,primarylivercancerDuetooneormorepotentiallyreversibleprecipitatingfactors

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7Pathogenesis(1)ToxicmaterialsderivedfromnitrogeneoussubstrateinthegutandbypasstheliverHEiscausedbyseveralfactorsactsynergisticallySeveralputativegut-derivedtoxinsidentified

8Pathogenesis(2)Postulatedfactors/mechanisms:AmmonnianeurotoxicitySynergisticneurotoxinsExcitatoryinhibitoryneurotransmittersandplasmaaminoacidimbalancehypothesisγ-Aminobutyricacid（GABA）/BZhypothesis

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10AmmonianeurotoxicityOverproductionand/orhypoeccrisisPoorhepato-cellularfunction:incompletemetabolismPortal-systemicencephalopathy:bypassAmmoniaintoxicationInterferewithcerebralmetabolism:Depletionofglutamicacid,asparticacidandATPDepressioncerebralbloodflowandoxygenconsumption

11AmmonianeurotoxicityElevationofammonia:detectedin60%~80%Absoluteconcentrationofammonia,ammoniametabolitesinbloodorcerebrospinalfluids,correlatesonlyroughlywiththepresenceorseverityofHEFewcases:withinnormalrange

12SynergisticneurotoxinsAmmoniaMercaptans(硫醇)Short-chainfattyacids

13Excitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalanceNeurotransmission:MediatedbybothexcitatoryandinhibitoryneurotransmittersTheirsynthesiscontrolledbybrainconcentrationoftheprecursoraminoacids

14Increasedaromaticaminoacids(AAAs)Tyrosine（酪氨酸）Phenylalanine（苯丙氨酸）Tryptophan（色氨酸〕DuetothefailureofhepaticdeaminationDecreasedbranched-chainaminoacids(BCAAs)Valine（缬氨酸）Leucine（亮氨酸）Isoleucine（异亮氨酸）DuetoincreasedmetabolismbyskeletalmuscleandkidneysorincreasedinsulinExcitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalance

15Imbalanceofplasmaaminoacid:MoreAAAsenterintoblood-brainbarrierandCNSDecreasedsynthesisofnormalneurotransmittersEnhancedsynthesisoffalseneurotransmittersOctopamine(苯乙醇胺)Tryptophan(-羟酪胺)Excitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalance

16γ-Aminobutyricacidhypothesisγ-Aminobutyricacid(GABA):PrincipalinhibitoryneurotransmittersGeneratedinthegutbybacteriaBypassesthediseasedorshuntedliverIncreasedblood-brainbarrierpermeability

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18PathohistologyBrainmaybenormalorcerebraledemaParticularlyinfulminanthepticfailureCerebraledemaislikelythesecondlychangesInpatientswithchronicliverdiseaseAstrocytes:increaseinnumberandenlargementInaverylong-standingcaseThincortex,lossofneuronsfibers,laminarnecrosis,pyramidaltractsdemyelination

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20ClinicalmanifestationClinically,HEmanifestsdiversesignsandsymptoms.Earlyforms,quitesubtlechangesinpersonalityorlevelofperformance.AsHEadvances,adisturbanceofconsciousness,impairedintellectualfunction,neuromuscularabnormalities,moodchanges,inversionofthesleepcycle,andslowedreactiontime.Day-nightreversalisoftenanearlymanifestation.

21ClinicalmanifestationCriteriaforclinicalstagesPersonalityandmentalchangesAsterixisAbnormalEEGpatterns

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23ClinicalGradingofHE

24ClinicalGradingofHE

25LaboratoryandothertestsSerumammoniaElevationofserumammonia:60%~80%particularlyinchronicHE(withportosystemicshunting)Electroencephalogram(EEG)SevereslowingwithfrequenciesinthethetaanddeltaEvokedpotentialsVariation,lackofspecificityandsensitivity

26Reitantrail-makingtestPsychometrictests----Numberconnectiontest

27WritingchartPsychometrictests----Digitsymboltest

28Diagnosisanddifferentialdiagnosis

29DiagnosisPatientswithsevereliverdiseaseand/orportalhypertension,portosystemicshuntingMentalchanges:confusion,somnolence,comaFactorsprecipitatingoraggravatingHEexistSeverelyimpairedliverfunctionand/orhyperammonemiaFlappingtremorandtypicalEEGchanges

30DiagnosisRecognitionofthelatentand/orsubclinicalHEImportantforviewoftheprevalenceofcirrhosisIntheabsenceofcharacteristicfeaturesAbnormalneuropsychiatricfunction:NumberconnectiontestDigitsymboltestsBlockdesignVisualreactiontimes

31DifferentialdiagnosisHypoglycemia（低血糖）UremiaDiabeticketoacidosis（糖尿病酮症酸中毒）Nonketotichyperosmolarsyndrome（非酮症高渗综合症）Subduralhematoma（硬膜下血肿）Cerebrospinalinfection（脑脊髓感染）

32Treatment

33ThegoalsoftherapyTotreattheunderlyingliverdiseaseandimprovemental.Themostimportantinitialaspectsofcarearetodiagnosetheconditionproperly,excludeothercausesofencephalopathy,andsearchforprecipitatingfactors

34一、IdentificationandtreatmentofprecipitatingfactorsTheseprecipitatingeventsmaybereadilyapparentorsubtle.Therefore,detaileddiscussionsandacarefulassessmentofchangesinlaboratoryvaluesarenecessary.SupportivecareCorrectionoffluid,electrolyte,glucose,acid-alkalineabnormalitiesManagementofcerebraledema,bacteremia

35二、DecreasingnitrogenloadandammoniaproductionsandabsorptionofenterictoxinsDecreasingammoniaproductionsDietaryproteinrestrictionBowelcleaning(clysis灌肠,catharsis导泻)NonabsorbabledisaccharidesAntibioticseradicationofHpIncreasingammoniametabolisms

36DietaryproteinrestrictionRestrictionofdietaryproteinatthetimeofacuteHEwithsubsequentincrementstoassessclinicaltoleranceisaclassiccornerstoneoftherapyProteinrestriction:0.81.0g/kg.dVegetableanddairysourcesarepreferabletoanimalproteinApositivenitrogenbalancepositiveefects

37BowelcleaningClysisLaxative(e.g.magnesiumcitrate硫酸镁)Notes:allenemasmustbeneutraloracidictoreduceammoniaabsorption

38NonabsorbabledisaccharidesLactulose（乳果糖）SyntheticdisaccharideFirst-linepharmacologicaltreatmentReleaselacticandaceticacidsbycolonicbacteriaDecreasingstoolpHtoabout5.5ReduceportionofammoniaanditsabsorptionEffectivein80%ofpatientsCause2~3softstool/d

39AntibioticsNeomycin（新霉素）:2~4g/DLitterisabsorbedImpairedhearingordeafness(longtermuse)Longtermuse(>1month)isnotadvisableMetronidozol（甲硝唑）:0.2gqidaseffectiveasneomycinRifaximin（利福昔明）

40IncreasingammoniametabolismsL-Ornithine-L-asparagicacid（L-鸟氨酸-L-天冬氨酸）Benzoate（苯甲酸盐），Phenylaceticacid（苯乙酸）Zinc(锌)Potassiumglutamate(谷氨酸钾)，sodiumglutamate(谷氨酸钠)Arginine(精氨酸)

41三、DrugsthataffectneurotransmissionAdministrationofBCAAsOralorparenteraladministrationL-dopa（左旋多巴）Precursoroftheneurotransmitternorepinephrinedopaminepenetrateblood-brainbarrierIncreasethenormalneurotransmitter

42四、GABA/BZreceptorantagonistsFlumazenil（氟马西尼）andothers:mayhaveatherapwuticroleinselectedpatientsAformalrecommendationontheuseofthesedrugscannotbemadeonthebasisofevidence-baseddata

43LivertransplantationUltimateanswertotheproblemofchronicHE

44SummaryKeyissuesoftheHEtopicClinicalmanifestations------ClinicalstagesofHEDiagnosisanddifferentialdiagnosisFactorsprecipitatingand/oraggravatingHE