HepaticEncephalopathy肝性腦病Definition(1)

Hepaticencephalopathy(HE)Itrepresentsareversibledecreaseinneurologicalfunction,baseduponthedisorderofmetabolismwhichiscausedbyseveredecompensatedliverdisease.嚴(yán)重肝病引起的以代謝紊亂為基礎(chǔ)的神經(jīng)、精神綜合征。主要臨床表現(xiàn)為意識障礙、行為失常和昏迷肝性腦病Definition(2)SubclinicalorlatentHE

diagnosedonlybyprecisementaltestsorEEG,noobviousclinicalandbiochemicalabnormalities

肝性腦病Incidence/prevalence

Universalfeatureofacuteliverfailure

50%~70%inchronichepaticfailureDifficulttoestimate肝性腦病EtiologyFulminanthepaticfailure

acutesevereviralhepatitis,drug/toxin,acutefattyliverofpregnancy

Duetoacutehepatocellularnecrosis

Chronicliverdiseasecirrhosisofalltypes,surgicallyinducedportal-systemicshunts,primarylivercancer

Duetooneormorepotentiallyreversibleprecipitatingfactors肝性腦病CommonprecipitatingfactorDeteriorationinhepaticfunctionDrugs

SedativespotentiallyhepatotoxicagentsGastrointestinalbleedingExcessivedietaryproteinUremia/azotemiaInfectionConstipationAnesthesiaandsurgeryHypoxiaDiuretics

hypokalemia,AlkalosishypovolemiaNitrogenousEncephalopathyNon-NitrogenousEncephalopathy肝性腦病肝性腦病Pathogenesis(1)

ToxicmaterialsderivedfromnitrogeneoussubstrateinthegutandbypasstheliverHEiscausedbyseveralfactorsactsynergisticallySeveralputativegut-derivedtoxinsidentified肝性腦病Pathogenesis(2)Postulatedfactors/mechanisms:

AmmonnianeurotoxicitySynergisticneurotoxinsExcitatoryinhibitoryneurotransmittersandplasmaaminoacidimbalancehypothesisγ-Aminobutyricacid（GABA）/BZhypothesis肝性腦病肝性腦病Ammonianeurotoxicity

Overproductionand/orhypoeccrisis

Poorhepato-cellularfunction:incompletemetabolismPortal-systemicencephalopathy:bypass

AmmoniaintoxicationInterferewithcerebralmetabolism:

Depletionofglutamicacid,asparticacidandATPDepressioncerebralbloodflowandoxygenconsumption

肝性腦病Ammonianeurotoxicity

Elevationofammonia:detectedin60%~80%Absoluteconcentrationofammonia,ammoniametabolitesinbloodorcerebrospinalfluids,correlatesonlyroughlywiththepresenceorseverityofHEFewcases:withinnormalrange肝性腦病Synergisticneurotoxins

AmmoniaMercaptans(硫醇)

Short-chainfattyacids肝性腦病Excitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalanceNeurotransmission:

MediatedbybothexcitatoryandinhibitoryneurotransmittersTheirsynthesiscontrolledbybrainconcentrationoftheprecursoraminoacids肝性腦病

Increasedaromaticaminoacids(AAAs)

Tyrosine（酪氨酸）Phenylalanine（苯丙氨酸）

Tryptophan（色氨酸〕

DuetothefailureofhepaticdeaminationDecreasedbranched-chainaminoacids(BCAAs)

Valine（纈氨酸）

Leucine（亮氨酸）

Isoleucine（異亮氨酸）

DuetoincreasedmetabolismbyskeletalmuscleandkidneysorincreasedinsulinExcitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalance肝性腦病Imbalanceofplasmaaminoacid:MoreAAAsenterintoblood-brainbarrierandCNSDecreasedsynthesisofnormalneurotransmittersEnhancedsynthesisoffalseneurotransmitters

Octopamine(苯乙醇胺)Tryptophan(-羥酪胺)

Excitatoryinhibitoryneurotransmitter&plasmaaminoacidsimbalance肝性腦病γ-Aminobutyricacidhypothesisγ-Aminobutyricacid(GABA):

PrincipalinhibitoryneurotransmittersGeneratedinthegutbybacteriaBypassesthediseasedorshuntedliverIncreasedblood-brainbarrierpermeability肝性腦病肝性腦病Pathohistology

Brainmaybenormalorcerebraledema

ParticularlyinfulminanthepticfailureCerebraledemaislikelythesecondlychangesInpatientswithchronicliverdisease

Astrocytes:increaseinnumberandenlargementInaverylong-standingcase

Thincortex,lossofneuronsfibers,laminarnecrosis

,pyramidaltractsdemyelination肝性腦病肝性腦病Clinicalmanifestation

Clinically,HEmanifestsdiversesignsandsymptoms.Earlyforms,quitesubtlechangesinpersonalityorlevelofperformance.AsHEadvances,adisturbanceofconsciousness,impairedintellectualfunction,neuromuscularabnormalities,moodchanges,inversionofthesleepcycle,andslowedreactiontime.Day-nightreversalisoftenanearlymanifestation.肝性腦病ClinicalmanifestationCriteriaforclinicalstages

PersonalityandmentalchangesAsterixisAbnormalEEGpatterns肝性腦病肝性腦病ClinicalGradingofHEGradeSymptomsSignEEGAbnormalitiesI-ProdromeAlteredsleeppatternsFluctuatingmood-

euphoria,depressionInappropriatebehaviorApathyLossofaffectWritingdifficultConstructionalapraxiaAsterixismaybepresentMaybepresentII-MildHEMildconfusionDisorientationDrowsiness（嗜睡）Asterixis(easilyelicitated)Ataxia（共濟(jì)失調(diào)）Fetorhepaticus肝臭AbnormalSlowerrhythms肝性腦病ClinicalGradingofHEGradeSymptomsSignEEGAbnormalitiesIII-ModerateHEMarkedconfusionArousablefromsleepResponsiveAsterixisRigidityoflimbsHyperflexiaClonusGraspingandsuckingreflexesBabinskiModerateIV-ComaUnconsciousnessUnresponsivetostimuliFlaccidlimbsDiminishedreflexesNomuscletonesignificant肝性腦病Laboratoryandothertests

Serumammonia

Elevationofserumammonia:60%~80%

particularlyinchronicHE(withportosystemicshunting)Electroencephalogram(EEG)

Severeslowingwithfrequenciesinthethetaanddelta

EvokedpotentialsVariation,lackofspecificityandsensitivity肝性腦病

Reitantrail-makingtestPsychometrictests----Numberconnectiontest肝性腦病WritingchartPsychometrictests----Digitsymboltest肝性腦病Diagnosisand

differentialdiagnosis肝性腦病Diagnosis

Patientswithsevereliverdiseaseand/orportalhypertension,portosystemicshuntingMentalchanges:confusion,somnolence,coma

FactorsprecipitatingoraggravatingHEexist

Severelyimpairedliverfunctionand/orhyperammonemia

FlappingtremorandtypicalEEGchanges肝性腦病Diagnosis

Recognitionofthelatentand/orsubclinicalHEImportantforviewoftheprevalenceofcirrhosisIntheabsenceofcharacteristicfeatures

Abnormalneuropsychiatricfunction:NumberconnectiontestDigitsymboltestsBlockdesignVisualreactiontimes肝性腦病Differentialdiagnosis

Hypoglycemia（低血糖）UremiaDiabeticketoacidosis（糖尿病酮癥酸中毒）Nonketotichyperosmolarsyndrome（非酮癥高滲綜合癥）Subduralhematoma（硬膜下血腫）Cerebrospinalinfection（腦脊髓感染）肝性腦病Treatment肝性腦病ThegoalsoftherapyTotreattheunderlyingliverdiseaseandimprovemental.Themostimportantinitialaspectsofcarearetodiagnosetheconditionproperly,excludeothercausesofencephalopathy,andsearchforprecipitatingfactors

肝性腦病一、IdentificationandtreatmentofprecipitatingfactorsTheseprecipitatingeventsmaybereadilyapparentorsubtle.Therefore,detaileddiscussionsandacarefulassessmentofchangesinlaboratoryvaluesarenecessary.SupportivecareCorrectionoffluid,electrolyte,glucose,acid-alkalineabnormalitiesManagementofcerebraledema,bacteremia

肝性腦病二、DecreasingnitrogenloadandammoniaproductionsandabsorptionofenterictoxinsDecreasingammoniaproductionsDietaryproteinrestrictionBowelcleaning(clysis灌腸,catharsis導(dǎo)瀉)NonabsorbabledisaccharidesAntibioticseradicationofHpIncreasingammoniametabolisms肝性腦病DietaryproteinrestrictionRestrictionofdietaryproteinatthetimeofacuteHEwithsubsequentincrementstoassessclinicaltoleranceisaclassiccornerstoneoftherapyProteinrestriction:0.81.0g/kg.dVegetableanddairysourcesarepreferabletoanimalproteinApositivenitrogenbalancepositiveefects肝性腦病BowelcleaningClysisLaxative(e.g.magnesiumcitrate硫酸鎂)

Notes:allenemasmustbeneutraloracidictoreduceammoniaabsorption肝性腦病NonabsorbabledisaccharidesLactulose（乳果糖）

SyntheticdisaccharideFirst-linepharmacologicaltreatmentReleaselacticandaceticacidsbycolonicbacteriaDecreasingstoolpHtoabout5.5ReduceportionofammoniaanditsabsorptionEffectivein80%ofpatientsCause2~3softstool/d肝性腦病AntibioticsNeomycin（新霉素）:2~4g/DLitterisabsorbedImpairedhearingordeafness(longtermuse)Longtermuse(>1month)isnotadvisableMetronidozol（甲硝唑）:0.2gqidaseffectiveasneomycinRifaximin（利福昔明）肝性腦病