肝性腦病英文課件

1、HEPATIC ENCEPHALOPATHYDEFINITIONl Hepatic encephalopathy is a reversible neuro-psychiatric state that complicates severe liver disease (HE).What dose it mean?fully reversible neuropsychiatric abnormalitiesin patients with liver dysfunctionaltered brain function is due to metabolic abnormalities excl

2、usion of unrelated neurologic and/or metabolic abnormalitiesfull reversibility of symptoms after improvement of liver function is considered to be direct proof of this causal relation AETIOLOGYEncephalopathy associated with Cirrhosis and portal hypertensionEncephalopathy associated with portal-syste

3、mic Bypass without hepatocellular diseaseEncephalopathy associated with Acute liver failureConcensus in Hepatic Encephalopathy, WCOG, 2001; in pressHepatic encephalopathy-A complication of cirrhosis of the liver020406080100 120 140 160020406080100Probability of complications (%)Gines et al. Hepatolo

4、gy (1987) 7, 1:122-128MonthsSpectrum of hepatic encephalopathyKey questionsMechanism: clearance of toxins central system - treatmentClinical manifestation: neuro-psychiatric changes - diagnosis and clinical grading PATHOGENETIC MECHANISMAmmonia toxicity theoryGama-aminobutyric aicd and endogenous be

5、nzodiazepines (GABA/BZ ) receptor complex theory False neurotransmitters theory & amino acid imbalance theoryOthers intestine Precipitating factors bacteria/protein GI bleeding infection liver removed hypokalemia and/or alkalosisportal-systemic shunt hypovolemia and/or hypoxia large protein meal

6、 blood-brain barrier constipation drugs(sedatives ) cerebral toxicity hypoglycemia Ammonia intoxication theoryNH3 NH4urea&H+Branched-chain amino acid /Aromatic amino acids 3-3.5 :1 (normal) 1 : 1 (cirrhosis)- the use of branched-chain amino acidAmino acid metabolic imbalance Tyrosine intestinal

7、bacterial decarboxylase L-dopa Tyrosine Phenylalanine Dopamine (Liver) Noradrenaline -Octopamine phenylethanolamine true false Sympathetic transmitter Brain function disturbedFalse neurotransmitterColon: proteinx(Brain)GABA/BZ receptor complex theoryGABA (from intestine produced by bacteria)Endogeno

8、us BZ- the use of benzodiazepine antagonistCLINICAL MANIFESTATION1. Disturbed consciousness: Sleep disturbance(change of sleep pattern to hypersomnia , or drowsiness ) Confusion including delirium Unconscious Clinical features2. Abnormal behavior 3. Intellectual deterioration (cognition)4. Abnormal

9、nerve reflexes Flapping tremor (asterixis)(Cont).Stage 1:Abnormal sleep Abnormal behavior (mood change e.g. euphoria/depression, strange behavior )Altered cognition ( decreased attention and calculation ability)Flapping tremor (+/-) EEG (+/-)Stage 2: Lethargic, Inappropriate behaviorDisorientation a

10、nd memory decreasedFlapping tremor (+), abnormal nerve reflexes(ataxia)EEG (+)Clinical gradingStage 3: Somnolence but can be aroused, marked confusion (delirium) Flapping tremor (+), abnormal nerve reflexes EEG (+)Stage 4: unconsciousness (can not be aroused) abnormal to loss of reflexes(Cont)Sub-cl

11、inical (Minimal) HE (0-1 stage)Clinically inapparent impairment in mental function sufficient to cause disruption in the routine of everyday living frequent in patients with cirrhosisthe state of which can only be detected by psychometric tests and evoked potential examination.Note1. Blood ammonia2.

12、Electroencephalogram(EEG)3. Evoked potentials*4. Psychometric tests*InvestigationDIAGNOSIS AND DIFFERENTIAL DIAGNOSIS Severe liver disease or portal-systemic shunt Neuropsychiatric manifestation Precipitants that induce HE Obvious impaired liver function tests, elevated blood ammonia level, flapping

13、 tremor and typical EEG change indicate the possible diagnosis Exclusion of organic brain diseasesDiagnosisComa induced by other causesDifferential diagnosisTREATMENT1.Identification & correction of the precipitating cause: Precipitating factors Drugs! Electrolyte imbalance hypokalemia/metabolic

14、 alkalosis (diuretics, vomiting, diarrhea, infusion) GI Bleeding Infection Constipation Large protein meal .2. Intervention to reduce the production & absorption of gut-derived ammonia & other toxins:1) Diet: reduce and modify dietary protein and maintain Calorie intake 2) Enemas (mild acid)

15、 and/or purgation3) Lactulose or lactitol4) Inhibition of gut bacteria: Antibiotics: neomycin(oral), metronidazole?5) Modification of colonic flora: probiotics?Modify colonic flora, resulting in displacement of urease-containing bacteria with lactobacillus Cathartic effectLower the colonic pH, resul

16、ting in the formation of nonabsorbable NH4 from NH3 in the colon 3. Stimulation of metabolic ammonia metabolism: 1) Ornithine-aspartate: enhancing the metabolism of ammonia to glutamine 2) Sodium glutamate or potassium glutamate, Arginine? 3) Sodium benzoate(oral): acting with glycine in the colon t

17、o form hippurate which can be excreted in the urine - applied in chronic HE, particularly in those with elevated blood ammonia4. Correct amino acid metabolic imbalance: infusion or oral administration of BCAA (branched-chain amino acid)5. GABA/BZ complex antagonist: flumazenil ( particularly if patient has been given benzodiazepines )6. Other