內(nèi)科學(xué)教學(xué)課件：07 肝性腦病

肝性腦病

HepaticEncephalopathy(HE)OutlineDefinitionClinicaltypesPathogenesisClinicalManifestationandGradingDiagnosisTreatmentPrognosisandPrevention2肝性腦病的定義（過去）稱“肝昏迷hepatic

coma”肝功能衰竭或門體分流引起的中樞神經(jīng)系統(tǒng)神經(jīng)精神綜合征，其主要臨床表現(xiàn)可以從人格改變、行為異常、撲翼樣震顫到出現(xiàn)意識(shí)障礙、昏迷和死亡。最常見與終末期肝硬化。如果肝臟功能衰竭和門體分流得以糾正，則HE可以逆轉(zhuǎn)，但（否則）易于反復(fù)發(fā)作。(內(nèi)科學(xué),供8及7年制,2005,p.521，人衛(wèi)版）(內(nèi)科學(xué),供8及7年制,2010,p.541，人衛(wèi)版）3SeverehepatocellulardysfunctionPortal-systemicshuntingIntrohepaticExtrahepatic4DefinitionHepaticencephalopathy(HE)isacomplex,potentiallyreversibleneuropsychiatricconditionthatoccursasaconsequenceofacuteorchronicliverdisease.Itischaracterizedbychangesofpersonality,consciousness,behaviorandneuromuscularfunctionHepaticencephalopathyisbrainandnervoussystemdamagethatoccursasacomplicationofliverdisorders.Itcausesdifferentnervoussystemsymptomsincludingchangesinreflexes,changesinconsciousness,andbehaviorchangesthatcanrangefrommildtosevere.Hepaticencephalopathyisasyndromeobservedinpatientswithcirrhosis.Hepaticencephalopathyisdefinedasaspectrumofneuropsychiatricabnormalitiesinpatientswithliverdysfunction,afterexclusionofotherknownbraindisease.肝性腦病的新定義晚近，肝性腦病的病因基礎(chǔ)由“嚴(yán)重肝病”修正為“嚴(yán)重的肝臟功能失調(diào)或障礙(dysfunction)”，包括3種主要類型A型：急性肝功能衰竭B型：不伴有內(nèi)在肝病但有嚴(yán)重門體分流C型：慢性肝病/肝硬化6曾經(jīng)用過的肝性腦病的分類Classification急性、慢性、終末期肝性腦病爆發(fā)性肝功能衰竭

(Fulminanthepaticfailure,FHF)門體分流性腦病

(Porto-systemicencephalopathy,PSE)亞臨床性或隱性或輕微型肝性腦病

(Subclinicalorlatentor

minimal

HE)Subtlesignsofhepaticencephalopathyareobservedinnearly70%ofpatientswithcirrhosis.肝性腦病的最新分類2001年有關(guān)肝性腦病的國(guó)際會(huì)議：肝性腦病的最新共識(shí)(ConsensusinHepaticEncephalopathy)A“急性(Acute)”B“分流(Bypass)”C“肝硬化(Cirrhosis)”8ConcensusinHE,WCOG2001TypeA

EncephalopathyassociatedwithAcuteliverfailure(ALFA-HE)TypeBEncephalopathyassociatedwithporto-systemicbypassandnointrinsichepatocellulardiseaseTypeCEncephalopathyassociatedwithcirrhosisorchronicliverdiseaseandportalhypertension9肝性腦病的最新分類

A型肝性腦病

急性肝衰竭相關(guān)的肝性腦病(ALFA-HE)EncephalopathyassociatedwithAcuteliverfailure可替代原用來代表一種急性HE的“暴發(fā)性肝衰竭(FHF)”的術(shù)語maybeusedtoreplacethetermfulminanthepaticfailure(FHF)采用ALFA-HE能夠避免將“急性肝衰竭伴發(fā)的HE”與“慢性肝病伴發(fā)的急性HE”的概念進(jìn)一步混淆。preventanyfurtherconfusionofacuteHEinchronicliverdiseasewithHEinacuteliverfailure.肝性腦病的最新分類

B型肝性腦病

它代表了門體性腦病(PSE)的純粹類型representsthepureformofportal-systemicencephalopathy臨床表現(xiàn)與那些患肝硬化伴腦病的患者類同，但確實(shí)沒有發(fā)現(xiàn)任何實(shí)質(zhì)性肝病ClinicalmanifestationsidenticaltothoseseeninpatientswithcirrhosisandHE臨床罕見rare（先天性血管畸形，門靜脈阻塞，etc>>門體旁路）只有在肝活檢提示正常組織學(xué)特征時(shí)才能診斷這種類型的腦病。shouldonlybediagnosedwhenanormalhistologyonliverbiopsy肝性腦病的最新分類

C型肝性腦病

包括了絕大多數(shù)的HE，即通常意義上的HE。thecategorycoveringthevastmajorityofpatientswithHE能夠糾正過去對(duì)于慢性HE定義的混淆理解correcttheconfusionforunderstandingthepreviousdefinitionof“ChronicHE”肝性腦病的最新分類

C型肝性腦病

C型指發(fā)生在慢性肝病階段的HE，無論其臨床表現(xiàn)是否急性patientsusuallyhaveaverywell-developedporto-systemiccollateralcirculationaswellascirrhosisatthetimeofdiagnosisofHEacuteorchronicepisodemightappear肝性腦病系統(tǒng)命名法類型系統(tǒng)命名亞型亞類A急性肝衰竭相關(guān)肝性腦病

B門體分流相關(guān)肝性腦病,不伴有內(nèi)在肝病

C伴肝硬化門脈高壓和/或門體分流的肝性腦病發(fā)作性肝性腦病有誘因自發(fā)性復(fù)發(fā)性（2次/年）持續(xù)性肝性腦病輕度（1級(jí)）重度（2-4級(jí)）治療依賴輕微肝性腦病CausesofHE(mainlyfromchronicliverdiseases)ViralhepatitisLatestageofschistosomalliverdiseaseAlcoholiccirrohsisDrug-inducedCardiaccirrhosisWilson’sDiseaseHemachromatosisPostportal-systemicshunt(smallpartfromacuteliverdiseasesorFHF)SevereacuteacuteviralhepatitisAcutetoxicliverdamageAcutedrug-inducedliverdisease(others)PrimarylivercancerAcutegestationalfattyliverdiseaseSeverebiliaryinfectionPortalthrombosisCausesofHE肝性腦病的病因(大部分由慢性肝病引起)肝炎肝硬化晚期血吸蟲性肝病酒精性肝硬化慢性藥物性肝病心源性肝硬化肝豆?fàn)詈俗冃?Wilson’sDisease)血色病門體分流術(shù)后(小部分見于急性肝病或FHF)重癥急性病毒性肝炎急性中毒性肝病急性藥物性肝病(更少見)原發(fā)性肝癌急性妊娠期脂肪肝嚴(yán)重膽道感染門靜脈血栓形成CommonprecipitantsofhepaticencephalopathyIncreasednitrogenloadGastrointestinalbleedingExcessdietaryproteinAzotemiaConstipationElectrolyteimbalanceHyponatremiaHypokalemiaMetabolicalkalosis/acidosisHypoxiaHypovolemiaDrugsNarcotics,tranquilizers,sedativesdiureticsMiscellaneousInfectionSurgerySuperimposedacuteliverdiseaseProgressiveliverdiseaseTransjugularintrahepaticportal-systemicshunt(TIPS)肝性腦病的常見誘因

Commonprecipitants(PSE常有)上消化道出血感染過量排鉀利尿大量放腹水高蛋白飲食飲酒安眠鎮(zhèn)靜藥物麻醉藥物便秘尿毒癥外科手術(shù)創(chuàng)傷etc18GeneralPathogenesisofHEBasis

Liverfunctionfailureand/orPSshuntMulti-dysfunctionofmetabolismnitrogenoussubstances

LiverDisease

+BrainDisease

=HepaticencephalopathyXGeneralPathogenesisofHE

肝性腦病的發(fā)病機(jī)制概論病理生理基礎(chǔ) 肝細(xì)胞功能衰竭and/or門體分流肝病(內(nèi)因)腦病(結(jié)果) (誘因)多方面的代謝紊亂，多種因素綜合作用的結(jié)果nitrogenoussubstances

UnderstandingofthepathogenesisofHEisbasedonthreepostulates

Thecausativemetabolictoxins(usuallynitrogenoussubstances)mostlikelyoriginateintheintestine.Becauseofportal-systemicshunts,thesetoxicsubstancesbypasstheliver,wheretheynormallyaremetabolized.Afterbypassingtheliver,thesetoxicsubstancescrosstheblood-brainbarrierandexertdirectorindirectneurotoxiceffectsonthecentralnervoussystem.Nosingleagentfulfillsallthreecriteria;thereforethepathogenesisofhepaticencephalopathyisbelievedtobemulti-factorial.

SeveralprocessesarethoughttohaveacausativeroleAccumulationoftoxinsinthebrain.Toxinsfromtheintestinescrosstheblood-brainbarrieratthelevelofendothelialcellsthatlinethecapillariesinthebrain.Theblood-brainbarrierinpatientswithhepaticencephalopathyisdisturbed,possiblybythetoxiceffectsofammonia.Analterationinplasmaaminoacidcomposition.Thisleadstoaccumulationof"false"neurotransmittersinthebrain.Increasesinneuroinhibitorysubstances,manganese,monoamines,orendogenousopiates.DiagrammaticPresentationLiverdiseasesMetabolismDetoxication

Intra/Extra-hepaticPSShunt

EnterogenicToxinsand/orNeuroactivesubstancesinsystemiccirculationConcentration

and/or

unbalancedChangesinBBBpermeabilityAbnormalinCNSprecipitants肝性腦病的發(fā)病機(jī)制圖示肝病代謝、解毒

肝內(nèi)外門體分流

體循環(huán)血中(腸源性)毒性和/或神經(jīng)活性物質(zhì)濃度和/或比例失調(diào)血腦屏障通透性改變中樞神經(jīng)系統(tǒng)異常25precipitantsPathogenesisofHE:

InteractionofvariousfactorsDisturbedliverfunctionNeurotoxinaminoacidimbalanceSwellinganddistributedfunctionofastrogliaChangesinNeurotransmittersChangesintheBBBChangesinpost-synapticreceptors26發(fā)病機(jī)制(pathogenesis)氨中毒學(xué)說(ammoniaintoxication)假神經(jīng)遞質(zhì)學(xué)說(falseneurotransmitterhypothesis)氨基酸失衡學(xué)說(aminoacidimbalance)

-氨基丁酸（GABA)及其受體的作用

(thegamma-amino-butyricacid/benzodiazepinesreceptorcomplex)協(xié)同作用學(xué)說

(synergisticactionsofmultipletoxins)……27發(fā)病機(jī)制

氨中毒學(xué)說（100多年的歷史）氨的形成：腸道(為主)、腎和骨骼肌氨的清除：尿素合成，谷氨酸和谷氨酰胺合成，腎排泄尿素和NH4+腸道pH的影響氨對(duì)中樞神經(jīng)系統(tǒng)的毒性：干擾能量代謝氨增高的原因及影響因素：(肝性腦病發(fā)生的誘因)28氨中毒學(xué)說(ammoniaintoxication)血氨增高的原因(causesofincreasedbloodammonia)氨生成增加(increasedsynthesis)腸道產(chǎn)氨(intestinal)↑

出血、腸粘膜淤血水腫、細(xì)菌叢生、氮質(zhì)血癥肌肉產(chǎn)氨(muscular)↑

躁動(dòng)、抽搐等使肌肉活動(dòng)增加。腺苷酸分解↑腎臟產(chǎn)氨(renal)↑

腎功能障礙29氨中毒學(xué)說(ammoniaintoxication)causesofincreasedbloodammoniaincreasedsynthesisintestinalproduction↑Muscularproduction↑Renalproduction↑2.reductioninabsorptionofammonia1.鳥氨酸循環(huán)障礙琥珀酰精氨酸精氨酸鳥氨酸瓜氨酸酶氨+CO2氨甲酰磷酸鹽尿素肝嚴(yán)重受損，底物,ATP,酶活性2.門--體分流氨繞過肝臟2.血氨清除減少（reductioninabsorptionofammonia)31proteinNH3NH3ureaNormalmetabolismLiverfailureproteinNH3NH3urea×BloodNH3↑proteinNH3NH3urea×BloodNH3↑ShuntingCirculation↑LiverfailureproteinNH3NH3urea×BloodNH3↑NH3↑↑LiverfailureShuntingCirculation氨對(duì)腦組織的毒性作用

(detrimentaleffectofammoniaonCNS)

干擾腦能量代謝disturbingenergymetabolism干擾腦內(nèi)神經(jīng)遞質(zhì)disturbingcerabralneutrotransmitter干擾神經(jīng)細(xì)胞膜離子轉(zhuǎn)運(yùn)disturbingmembraneiontransport36氨對(duì)腦組織的毒性作用

(detrimentaleffectofammoniaonCNS)

增加腦水腫（A型HE，即爆發(fā)性肝衰時(shí)）BrainedemaAlzheimer氏II型星形細(xì)胞增生（PSE時(shí)）改變基因表達(dá)Alzheimer’stypeIIastrocytosis線粒體通透性轉(zhuǎn)變(MPT)Mitochondrialpermeabilitychanges371.干擾腦能量代謝NADHNADNH3NH3

-酮戊二酸谷氨酸谷氨酰胺ATP（2）NADH消耗過多，呼吸鏈遞氫受阻，ATP產(chǎn)生（3）ATP消耗過多。（1）進(jìn)入三羧酸循環(huán)的

-酮戊二酸，ATP產(chǎn)生38ATP

encephalopathy?39草酰乙酸琥珀酸檸檬酸α-酮戊二酸谷氨酸↓谷氨酰胺↑＋NH3↑ATPNADHNAD＋NH3↑丙酮酸乙酰輔酶A乙酰膽堿↓膽堿＋NH3↑×γ-氨基丁酸↑NH3↑×2.干擾腦內(nèi)神經(jīng)遞質(zhì)—a神經(jīng)介質(zhì)成分改變2b腦內(nèi)神經(jīng)遞質(zhì)異常興奮性遞質(zhì)(excitingneurotransmitters)↓抑制性遞質(zhì)(inhibitingneurotransmitters)↑腦功能抑制disturbedbrainfunction3.干擾神經(jīng)細(xì)胞膜離子轉(zhuǎn)運(yùn)氨可干擾神經(jīng)細(xì)胞膜上的鈉泵的活性，影響復(fù)極后期膜的離子轉(zhuǎn)運(yùn)，使膜電位變化和興奮性異常。氨與鉀離子有競(jìng)爭(zhēng)作用，影響在神經(jīng)細(xì)胞膜內(nèi)外的正常分布，從而干擾神經(jīng)的傳導(dǎo)活動(dòng)。細(xì)胞Na+-K+-ATP酶Na+Na+K+K+NH342增加腦水腫，星形細(xì)胞功能異常

NH3谷氨酸谷氨酰胺↑

（ATP）谷氨酰胺合成酶（星形細(xì)胞）43AmmoniaandastrocytosisAmmonia-->Glutamine(Gln)Glutaminesynthetase(GS):anastroglia-specificenzyme.InHEresultingfromacuteliverfailure:OsmoticactionofGlninalargedegreeresponsibleforcerebraledemaandedema-associateddisturbanceofcerebralbloodflowandionichomeostasis.44AlzheimertypeⅡastrocytes45Ammonia:centralinpathogenesisofHEAlzheimertypeIIastrocytosisoccursin:HumanPSEbrainBrainsofinfantswithhyperammonemiaduetoureacycleenzymopathiesBrainsofratewithurease-inducedhyperammonemiaCulturesratastrocytesexposedammonia46改變基因表達(dá)星形細(xì)胞谷氨酸鹽載體(GLT-1)星形細(xì)胞結(jié)構(gòu)蛋白膠質(zhì)纖維酸性蛋白外周型苯二氮卓受體水通道4（水通道4可能與高血氨狀態(tài)下的星形膠質(zhì)細(xì)胞的水腫有關(guān)）47線粒體通透性轉(zhuǎn)變（MPT）

線粒體內(nèi)膜對(duì)小溶質(zhì)通透性增加（離子<1500Da分子）氨→上調(diào)外周型BZ受體(PBR)→自由基產(chǎn)生（氧和亞硝基）→氧化/亞硝化應(yīng)激→MPT→線粒體功能障礙谷氨酰胺也可直接誘導(dǎo)培養(yǎng)的星狀細(xì)胞發(fā)生MPT，也能形成自由基。結(jié)果：線粒體內(nèi)膜電位消除線粒體基質(zhì)出現(xiàn)膠體滲透性腫脹氧化磷酸化缺陷ATP合成停止自由基產(chǎn)生大腦功能發(fā)生障礙48假性神經(jīng)遞質(zhì)學(xué)說(FNThypothesis)假性神經(jīng)遞質(zhì)

(falseneurotransmitter,FNT)

49HOHOCHOHCH2NH2CHOHCH2NH2HOCHOHCH2NH2HOHOCH2CH2NH2HOHOCHOHCH2NH2CHOHCH2NH2HOCHOHCH2NH2HOHOCH2CH2NH2去甲腎上腺素noradrenaline苯乙醇胺phenylethanolamine多巴胺dopamine羥苯乙醇胺octopamineFNT形成的機(jī)制(mechanismofFNTsynthesis)52gutliverbrainNormalmetabolism酪胺苯乙胺TyraminephenylethylamineTyrosinephenylalanine酪氨酸苯丙氨酸酪胺苯乙胺MAOTyrosinetyraminephenylalaninephenylethylamineLiverfailureTyraminephenylethylanine酪胺苯乙胺TyrasinetyraminephenylalaninephenylethylamineLiverFailure肝衰竭Shunting門-體分流Tyraminephenylethylamine↑↑酪胺苯乙胺酪胺苯乙胺TyrasinetyraminephenylalaminephenylethylamineLiverfailure

肝衰竭Shunting門-體分流Octopaminephenylethanolamine

羥苯乙醇胺苯乙醇胺酪氨酸苯丙氨酸酪胺苯乙胺-羥化酶FNT↑replacingNNT（取代）Disturbingneurotransmission神經(jīng)沖動(dòng)傳遞受阻Encephalopathy腦病部位？FNT引起腦病的機(jī)制(possiblemechanismleadingtoencephalopathy)FNT取代NNT的部位網(wǎng)狀結(jié)構(gòu)上行激動(dòng)系統(tǒng)昏迷紋狀體撲翼樣震顫Whenhealthy：支鏈氨基酸/芳香族氨基酸=3.0～3.5branchedaa/aromaticaa

（BCAA)(AAA)Whenliverfailure:BCAA↓/AAA↑＝0.6～1.2氨基酸不平衡（Aminoacidimbalance）芳香族AA(AromaticAA，catalysedinliver)

支鏈AA(BranchedAA，catalysedinskeletalmus)

血漿氨基酸失衡學(xué)說

(aminoacidimbalancehypothesis)氨基酸失衡的機(jī)制(pathogenesisofAAimbalance)liverfailure肝衰竭胰高血糖素glucagon↑c(diǎn)atabolism↑胰島素insulin↑utilizationBCAA↑AAAcatabolism↓bloodAAA↑BloodBCAA↓氨基酸失衡引起腦病的機(jī)制(detrimentaleffectofaaimbalanceonencephalopathy)61苯乙胺苯乙醇胺脫羧-羥化酪胺羥苯乙醇胺脫羧-羥化AAA↑BCAA↓血腦屏障5-羥色氨酸5-羥色胺↑羥化脫羧多巴多巴胺↓去甲腎上腺素↓×××苯丙aa酪aa色aa氨基酸失衡引起腦病的機(jī)制1.CerebralFNT↑2.CerebralNNT↓3.Cerebral5-HT↑5-HT既是抑制性介質(zhì)，又是假性神經(jīng)介質(zhì)！63detrimentaleffectofaaimbalanceonencephalopathy氨基酸失衡引起腦病的機(jī)制1.CerebralFNT↑2.CerebralNNT↓3.Cerebral5-HT↑(inhibitoryandFNT)5-HT既是抑制性介質(zhì)，又是假性神經(jīng)介質(zhì)！γ-氨基丁酸學(xué)說GABA/benzodiazepines(BZ)receptorcomplexandhepaticencephalopathy65GABA:mostimportantinhibitoryneurotransmitter是最主要的抑制性神經(jīng)介質(zhì)

Whenliverfailure，GABAergic↑：1.IncreasedGABAinbloodandbrain腸道來源GABA在肝內(nèi)清除

&bypass

BBB對(duì)GABA的通透性↑GABAinbrain↑2.post-synapticreceptors

腦突觸后膜GABA受體↑

66Cl-Cl-Cl-Cl-R囊泡GABAGABA作用示意圖HE-relatedGABA-Areceptor,aBZreceptor,barbituratereceptorandachlorideionospherecomposeofaGABA/BZreceptorcomplex,resultingintheincreasedinhibitoryGABAergictoneafteractivationbyGABA,BZorbarbiturates.Ammonia:centralinpathogenesisofHEPathologyofHETheliveritselfThecentralnervoussystemWhenFHFCerebraledemaWhenPSEAstrocytosis原漿性星型細(xì)胞肥大增多Thinnercerebrallayer大腦皮質(zhì)薄Disappearofneuronsandfibers神經(jīng)元及神經(jīng)纖維消失71ClinicalManifestationEncephalopathy腦病表現(xiàn)Hepatopathy肝病表現(xiàn)Hepaticcomplications肝病并發(fā)癥的表現(xiàn)ClinicalManifestationofHEwide,complicated,individualizedFromsubclinicaltoclinicalAcute,chronic,acute-on-chronic,terminalAccompanyimgdiseasesMental,intellectualandbehavioralchangesNeuro-skeletalsystemfetorhepaticus肝性腦病的臨床表現(xiàn)癥狀譜廣、復(fù)雜且個(gè)體差異大亞臨床－－臨床急性、慢性、慢性基礎(chǔ)上的急性、終末期伴隨疾病意識(shí)、智力、行為性格神經(jīng)肌肉系統(tǒng)肝臭fetorhepaticus737475ClinicalfeaturesofliverdiseaseandcomplicationsOfliverdisease肝病表現(xiàn)：肝功能減退（黃疸、肝臭、出血傾向）和門脈高壓癥（腹水、脾大和脾功能亢進(jìn)）Ofitscomplications肝病并發(fā)癥的表現(xiàn)：食管-胃底曲張靜脈破裂出血、自發(fā)性腹膜炎、嚴(yán)重的電解質(zhì)紊亂、肝腎綜合征等76ClinicalfeaturesofHE認(rèn)知、精神和運(yùn)動(dòng)障礙睡眠障礙：血漿褪黑素分泌時(shí)相紊亂注意力持續(xù)時(shí)間縮短性格改變行為改變撲翼樣震顫，肌針攣智能改變（對(duì)時(shí)空、人物概念模糊，言語、書寫困難，算術(shù)緩慢或錯(cuò)誤等）意識(shí)障礙（昏睡、淺昏迷、深昏迷甚至死亡）77ClinicalfeaturesofHEcognitive,mental,anddiskineticchangesSleepingdisturbanceConcentration/orientationPersonalcharacteristicsBehavioralchangesFlappyingtremor（asterixis）IntellectualchangesGradingsofHE79撲擊（翼）樣震顫

（flappingtremor或asterixis）為HE患者最具特征的神經(jīng)系統(tǒng)體征。檢查方法：囑患者兩臂伸直，手指分開，可見到掌指關(guān)節(jié)和腕關(guān)節(jié)快速的屈曲和伸展運(yùn)動(dòng)，呈撲翼樣抖動(dòng)，同時(shí)手向外側(cè)偏斜，有時(shí)甚至累及肘關(guān)節(jié)、肩關(guān)節(jié)、頸部和面頜部。GradingSystemforHEOther

Tests

用于肝性腦病的輔助檢查肝功能常規(guī)檢查血氨(慢性腦病)： 靜脈10-35mol/L， 動(dòng)脈0.5-2倍腦電圖(EEG)：波、波、三相波、波腦地形圖誘發(fā)電位：VEP、AEP、SEP臨界視覺閃爍頻率（CFF）81用于肝性腦病的輔助檢查心理智能測(cè)驗(yàn)簡(jiǎn)易智力測(cè)試(psychometrictests)數(shù)字連接試驗(yàn)(numberconnectiontest)年齡、教育、視力、環(huán)境現(xiàn)代神經(jīng)影像學(xué)技術(shù)CTMRIMRS（磁共振波譜分析）PET（正電子發(fā)射斷層掃描）Sensitivity?Specificity?82Electrocerebrography腦電圖肝性腦病分級(jí)腦電圖表現(xiàn)0級(jí)正常

波節(jié)律1級(jí)不規(guī)則的本底活動(dòng)（

和θ節(jié)律）2級(jí)持續(xù)的θ波，偶有

波3級(jí)普遍的θ波，一過性的含有棘波和慢波的多相綜合波4級(jí)持續(xù)的

波，大量的含有棘波和慢波的綜合波腦電圖診斷特異性不強(qiáng)腦電圖對(duì)MHE和1級(jí)HE的診斷價(jià)值較小EEGspectrumanalysis光譜分析肝性腦病分級(jí)平均優(yōu)勢(shì)波頻率(c/s)θ波比例(%)

波比例(%)功效(μV2)0≥6.4<35<701≥6.4≥35<702<6.4<703<6.4≥70≥2504<6.4≥70<250Cerebro-topography腦地形圖腦地形圖能把各種頻率的改變部位、范圍及其量的差別，用彩色圖形客觀地顯示出來數(shù)字連接試驗(yàn)

Numberconnectiontest(NCT)NCTA NCTB87Base-lineNCTdataofthecontrolgroup

(meanandstandarddeviationinseconds)

NCTA NCTB n MeanSD MeanSD Wholegroup 31.6 11.8 78.7 33.424918~30years 23.2 7.0 55.2 15.2 8131~40years 29.2 8.9 72.626.8 5241~50years 34.8 10.3 84.127.1 4651~60years 38.1 10.3 95.228.6 39>60years 45.0 11.9 121.940.0 31Bluecollar 35.1 11.9 92.536.0130Whitecollar 27.9 10.8 63.622.6 108Schoolgrade1 43.3 11.4 117.635.852Schoolgrade2 31.2 9.9 75.423.5127Schoolgrade3 23.8 8.0 56.019.370 WeissenbornK.etal88175cirrhoticpatients

353normalcontrol

ResultsofNCTageControl Cirrhotic Abnormal(％) no.score(xs)no.score(xs)#

25~34 8226.78.82435.614.6 10(41.7)35~44 7634.212.73247.218.6 15(46.9)45~54 7439.813.84955.715.4 24(48.9)55~64 6952.713.53874.515.8 19(50.0)≥65 5569.914.83289.716.1 17(53.1)

合計(jì) 35647.813.217578.418.3 85(48.6)

CirrhoticgroupNCTwassignificantlylongerthanthatinnormalcontrolgroupinallagegroups.(P<0.05~0.002)

聶玉強(qiáng)等中華消化雜志2001;21(4):67789韋氏成人智力量表

IntellectualquotienttestIQ(WAIS)

語言

information 常識(shí)

comprehension 理解

arithmetic 算術(shù)

similarity 相似性

digitspan 數(shù)字廣度

vocabulary 詞匯 操作

digitsymbol

數(shù)字符號(hào)

picturecompletion 填圖

blockdesign

木塊圖

picturearrangement 圖片排列

objectassembly 圖象組合90

Digitsymboltest

91Neuro-electro-physiologicaltests

神經(jīng)生理測(cè)定視覺誘發(fā)電位

Visualevokedpotentials(VEPs)腦干聽覺誘發(fā)電位Brainstemauditory-evokedpotentials(BAEPs)軀體感覺誘發(fā)電位Somatosensory-evokedpotentials(SSEPs)

較心理智能檢測(cè)更客觀不受年齡和教育的影響不需要訓(xùn)練敏感性高于心理智能檢測(cè)需要復(fù)雜儀器臨界視覺閃爍頻率CFF通過視覺功能的變化，判定視網(wǎng)膜膠質(zhì)細(xì)胞的病變，間接反映大腦膠質(zhì)星狀細(xì)胞腫脹和神經(jīng)傳導(dǎo)功能障礙檢測(cè)MHE的常規(guī)方法，可定量不受文化程度、年齡、職業(yè)等影響易受藥物、疲勞等干擾92MRIC型肝性腦病患者M(jìn)RI檢查提示腦水腫Hepatology.2006Apr;43(4):698-706

T1-加權(quán)MRI蒼白球高信號(hào)與門體性肝性腦病的發(fā)生有相關(guān)性

JGastroenterolHepatol.2006May;21(5):902-7

MRS磁共振波譜分析AprotonmagneticresonancespectrumillustratingthedifferentpeaksandinparticulartheGlx(glutamate/glutamine)peakwhichisincreasedinthepatientswithoverthepaticencephalopathy(NAA:N-acetylaspartate;Cho:choline;Cr:creatine).Currentandfutureapplicationsofmagneticresonanceimagingandspectroscopyofthebraininhepaticencephalopathy

WorldJGastroenterol.2006May21;12(19):2969-78

MRS檢測(cè)的代謝異常與神經(jīng)精神異常相關(guān)治療后MRS可恢復(fù)正常該技術(shù)可客觀地檢測(cè)患者，并評(píng)價(jià)不同治療手段對(duì)患者是否有效。95PETPositronemissiontomography(PET)analysesofahealthypersonanda47-year-oldalcoholiccirrhoticpatientwithmildhepaticencephalopathy.Thebloodflowthroughthebrain(i.e.,cerebralbloodflow[CBF])differsonlyminimallybetweenthetwosubjects.However,thecerebralmetabolicrateforammonia(CMRA)andthepermeabilitysurfaceareaproduct(PS)-ameasureoftheextenttowhichammoniacanpasstheblood-brainbarrierandenterthebrain,

aresignificantlyincreasedinthealcoholicpatient,asindicatedbythewiderdistributionandenhancedbrightnessofthelightareas.DiagnosisofHE基于臨床，用排除法Based

clinicalfindings,withthemethod

ofexclusionMainsuggestiveevidence主要依據(jù)：嚴(yán)重肝病和/或門體分流、腦病、誘因Significantreference重要參考價(jià)值：血氨、撲翼樣震顫、EEG、誘發(fā)電位Psychometrictest簡(jiǎn)易智力測(cè)試數(shù)字連接試驗(yàn)CFF臨界視覺閃爍頻率9798PracticalstepsfordiagnosisEncephalopathy,yesorno?

Ifyes,isitHE?Excludetheothercauses

Clinicalgrading,acute,and/orchronic

Minimal(subclinical)HE?99診斷的實(shí)際操作當(dāng)肝病患者出現(xiàn)相關(guān)神經(jīng)系統(tǒng)癥狀時(shí)，首先要確定有無腦病存在

如果有腦病，則要明確是否為肝性腦病

除外其他原因引起的腦病進(jìn)一步明確肝性腦病的臨床分級(jí)、急性或慢性，肝性腦病誘因和肝病病因100癥狀型肝性腦病的診斷肝硬化、肝癌、暴發(fā)性肝功能衰竭、門體分流術(shù)后和TIPS術(shù)后的患者如出現(xiàn)神經(jīng)、精神功能紊亂，應(yīng)考慮肝性腦病的可能性。如患者出現(xiàn)睡眠節(jié)律改變、認(rèn)知障礙、定向力和意識(shí)活動(dòng)障礙、精神錯(cuò)亂、昏睡或昏迷等癥狀，伴有撲翼樣震顫、明顯肝功能損害、血氨升高或腦電圖典型改變，結(jié)合患者的病史和有肝性腦病的誘因存在，則肝性腦病的診斷可以成立。101Minimal

HE診斷標(biāo)準(zhǔn)存在能引起MHE的疾病如肝硬化或先天性的門體分流臨床檢查精神狀態(tài)正常,無明顯的肝性腦病癥狀通過神經(jīng)心理學(xué)測(cè)試以及神經(jīng)生理學(xué)檢查發(fā)現(xiàn)異常排除能引起神經(jīng)學(xué)異常的其它因素如飲酒、視力障礙等很重要！！職業(yè)作業(yè)的要求！Differential

Diagnosis

肝性腦病的鑒別診斷代謝性：低鈉、低血糖、糖尿病性酮癥和高滲性昏迷、缺氧、尿毒癥、Wilson病中毒性：酒精、藥物(尤鎮(zhèn)靜劑)、重金屬顱內(nèi)病變：出血、缺血、占位、炎癥感染、癲癇功能性精神病102肝性腦病的發(fā)病機(jī)制圖示肝病代謝、解毒

肝內(nèi)外門體分流

體循環(huán)血中(腸源性)毒性和/或神經(jīng)活性物質(zhì)濃度和/或比例失調(diào)血腦屏障通透性改變中樞神經(jīng)系統(tǒng)異常104precipitantsTreatment

in

GeneralEarlyrecognitionandprompttreatmentNospecificeffectivetherapyyetComprehensiveTxPrimarydiseasesPrecipitatingfactorsSupportiveTxDecreasetheproductionandabsorptionofenterogenictoxinsIncreasethecatabolismofthosefactorsCorrecttheimbalanceofaaaothers肝性腦病的治療–總論

Treatment

in

GeneralEarlyrecognitionandprompttreatment尚無特效療法針對(duì)病理生理基礎(chǔ)，采取綜合措施治療原發(fā)病去除誘因?qū)ΠY支持治療減少腸內(nèi)毒物生成和吸收促進(jìn)有毒物質(zhì)的代謝清除糾正氨基酸代謝的紊亂其它106TreatmentofHEBasedonSupportivemeasuresCorrectionofprimarydiseasesCorrectionofprecipitatingfactorsAdministrationofmedicationthatdecreasetheproduction/absorptionoftoxinsorantagonizetheireffectsonbrain107PracticeGuidelines:HETreatmentGoalsProvisionofSupportiveCareIdentificationandRemovalofPrecipitatingFactorsReductionofNitrogenousLoadfromtheGutAssessmentoftheNeedforLongTermTherapyATBlei,JCordoba,thePracticeParametersComitteeoftheAmCollegeofGastroenterolTheAmericanJournalofGastroenterology2001;96(7):1968-1976PracticeGuidelines:HETreatmentOptions(basedonseveral,non-mutuallyexclusiveoptions)NutritionalManagementProtein,BCAA,ZincReductionintheNitrogenousLoadArisingfromtheGUTBowelCleaning;Non-absorbabledisaccharides;antibiotics;othersDrugsthatAffectNeurotransmissionsFlumazenil,bromocriptineManipulationoftheSplanchnicCirculationATBlei,JCordoba,thePracticeParametersComitteeoftheAmCollegeofGastroenterolTheAmericanJournalofGastroenterology2001;96(7):1968-1976HETreatmentPrecipitantsofHEshouldbecorrectedUGIB,infection,Hydro-electrolytes,acid-base,CautiousinMentaldrugs,alcoholTreatmentstodecreaseintestinalammoniaproductionDietary:diet,energy,vegetableproteinsEnemaandcatharsis:aceticacid,magnesiumsulfate,lactuloseInhibitbacteria:neomycin,metronidazole,rifaximin,lactulose,lactirol,Reconstructionofintestinalmicroecology肝性腦病的治療--個(gè)論P(yáng)recipitantsofHEshouldbecorrected去除誘因控制UGIB和感染，糾正水鹽酸堿失衡慎用精神抑制類藥物，戒酒Treatmentstodecreaseintestinalammoniaproduction減少腸內(nèi)毒物的生成和吸收飲食：禁食、營(yíng)養(yǎng)能量、植物蛋白(40-60g/L)灌腸和導(dǎo)瀉：醋酸、硫酸鎂、乳果糖抑制細(xì)菌生長(zhǎng)：新霉素、甲硝唑、利福昔明、乳果糖(lactulose)、乳梨醇(lactirol)、重建微生態(tài)蛋白質(zhì)的攝入

(dietary

protein

restriction)有肝性腦病病史者：40－70克/日輕微肝性腦?。翰槐亟车鞍?-2級(jí)肝性腦?。?0克/日,每3-5天增加10克，恢復(fù)后0.8-1.0克/千克體重/天3-4級(jí)肝性腦?。航箯奈改c道補(bǔ)充蛋白質(zhì)，鼻飼或靜脈注射葡萄糖Vegetable

protein112

肝性腦病的治療--個(gè)論

乳果糖(Lactulose)不吸收的雙糖(nonabsorptable

disaccharide)輕瀉劑(滲透壓)

(osmotic

laxative)在結(jié)腸被分解為乳酸和醋酸，使腸腔呈酸性，減少氨的形成和吸收參與抑制其它有害菌群的生長(zhǎng)用法：口服，灌腸劑量控制：每日2－3次稀軟便/15-30ml

tid

s