20 hepatic enchephalopathy

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20 hepatic enchephalopathy

  1. 1. HEPATIC ENCEPHALOPATHY GAO XIANG Department of Gastroenterology The First Affiliated Hospital
  2. 2. DEFINITION <ul><li>Hepatic encephalopathy is a reversible neuro-psychiatric state that complicates severe liver disease(HE). </li></ul>
  3. 3. AETIOLOGY <ul><li>Encephalopathy associated with C irrhosis and portal hypertension </li></ul><ul><li>Encephalopathy associated with portal-systemic B ypass without hepatocellular disease </li></ul><ul><li>Encephalopathy associated with A cute liver failure </li></ul>Concensus in Hepatic Encephalopathy, WCOG, 2001; in press
  4. 4. Hepatic encephalopathy- A complication of cirrhosis of the liver 0 20 40 60 80 100 120 140 160 0 20 40 60 80 100 Probability of complications (%) Gines et al. Hepatology (1987) 7, 1:122-128 Months
  5. 5. Key questions <ul><li>Mechanism : </li></ul><ul><li>clearance of toxins central system </li></ul><ul><li>--- treatment </li></ul><ul><li>Clinical manifestation: </li></ul><ul><li>neuro-psychiatric changes </li></ul><ul><li>--- diagnosis and clinical grading </li></ul>
  6. 6. PATHOGENETIC MECHANISM <ul><li>Ammonia toxicity theory </li></ul><ul><li>False neurotransmitters theory </li></ul><ul><li>& amino acid imbalance theory </li></ul><ul><li>Gama-aminobutyric aicd and endogenous benzodiazepines (GABA/BZ ) receptor complex theory </li></ul><ul><li>Others </li></ul>
  7. 7. <ul><li>intestinal Precipitating factors </li></ul><ul><li>bacteria/protein  GI bleeding </li></ul><ul><li> infection </li></ul><ul><li>liver removed  hypokalemia and/or alkalosis </li></ul><ul><li>portal-systemic shunt  hypovolemia and/or hypoxia </li></ul><ul><li> large protein meal </li></ul><ul><li>blood-brain barrier  constipation </li></ul><ul><li> drugs(sedatives ) </li></ul><ul><li>cerebral toxicity  hypoglycemia </li></ul>Ammonia intoxication theory NH 3 NH 4 urea & H +
  8. 9. <ul><li>Branched-chain amino acid / Aromatic amino acids </li></ul><ul><li>3-3.5 :1 (normal) </li></ul><ul><li><1 : 1 (cirrhosis) </li></ul><ul><li>------ the use of branched-chain amino acid </li></ul>Amino acid metabolic imbalance
  9. 10. <ul><li>Tyrosine intestinal bacterial decarboxylase </li></ul><ul><li>L-dopa Tyrosine Phenylalanine </li></ul><ul><li>Dopamine (Liver) </li></ul><ul><li>Noradrenaline Octopamine  -phenylethanolamine </li></ul><ul><li>true false </li></ul><ul><li>Sympathetic transmitter </li></ul><ul><li>Brain function disturbed </li></ul>False neurotransmitter Colon: protein x ( Brain )
  10. 11. GABA/BZ receptor complex theory <ul><li>GABA (from intestine produced by bacteria) </li></ul><ul><li>Endogenous BZ </li></ul>--- the use of benzodiazepine antagonist
  11. 12. CLINICAL MANIFESTATION
  12. 13. <ul><ul><ul><li>1. Disturbed consciousness : </li></ul></ul></ul><ul><ul><ul><li>Sleep disturbance </li></ul></ul></ul><ul><ul><ul><li>(change of sleep pattern to hypersomnia , or drowsiness ) </li></ul></ul></ul><ul><ul><ul><li>Confusion including delirium </li></ul></ul></ul><ul><ul><ul><li>Unconscious </li></ul></ul></ul>Clinical features
  13. 14. <ul><ul><ul><li>2. Abnormal behavior </li></ul></ul></ul><ul><ul><ul><li>3. Intellectual deterioration (cognition) </li></ul></ul></ul><ul><ul><ul><li>4. Abnormal nerve reflexes </li></ul></ul></ul><ul><ul><ul><li>Flapping tremor (asterixis) </li></ul></ul></ul>(Cont).
  14. 16. <ul><li>Stage 1: </li></ul><ul><li>Abnormal sleep </li></ul><ul><li>Abnormal behavior </li></ul><ul><li>(mood change e.g. euphoria/depression, strange behavior ) </li></ul><ul><li>Altered cognition ( decreased attention and calculation ability) </li></ul><ul><li>Flapping tremor (+/-) </li></ul><ul><li>EEG (+/-) </li></ul><ul><li>Stage 2: </li></ul><ul><li>Lethargic, </li></ul><ul><li>Inappropriate behavior </li></ul><ul><li>Disorientation and memory decreased </li></ul><ul><li>Flapping tremor (+), abnormal nerve reflexes(ataxia) </li></ul><ul><li>EEG (+) </li></ul>Clinical grading
  15. 17. <ul><li>Stage 3: </li></ul><ul><li>Somnolence but can be aroused, </li></ul><ul><li>marked confusion (delirium) </li></ul><ul><li>Flapping tremor (+), abnormal nerve reflexes </li></ul><ul><li>EEG (+) </li></ul><ul><li>Stage 4: </li></ul><ul><li>unconsciousness (can not be aroused) </li></ul><ul><li>abnormal to loss of reflexes </li></ul>(Con’t)
  16. 19. <ul><li>Sub-clinical ( Minimal ) HE (0-1 stage) </li></ul><ul><li>Clinically inapparent impairment in mental function </li></ul><ul><li>sufficient to cause disruption in the routine of everyday living </li></ul><ul><li>frequent in patients with cirrhosis </li></ul><ul><li>the state of which can only be detected by psychometric tests and evoked potential examination. </li></ul>Note
  17. 20. <ul><ul><ul><li>1. Blood ammonia </li></ul></ul></ul><ul><ul><ul><li>2.Electroencephalogram(EEG) </li></ul></ul></ul><ul><ul><ul><li>3. Evoked potentials* </li></ul></ul></ul><ul><ul><ul><li>4. Psychometric tests* </li></ul></ul></ul>Investigation
  18. 21. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
  19. 22. <ul><ul><ul><li>Severe liver disease or portal-systemic shunt </li></ul></ul></ul><ul><ul><ul><li>Neuropsychiatric manifestation </li></ul></ul></ul><ul><ul><ul><li>Precipitants that induce HE </li></ul></ul></ul><ul><ul><ul><li>Obvious impaired liver function tests, elevated blood ammonia level, flapping tremor and typical EEG change indicate the possible diagnosis </li></ul></ul></ul>Diagnosis
  20. 23. <ul><li>Coma induced by other causes </li></ul>Differential diagnosis
  21. 24. TREATMENT
  22. 25. <ul><li>Identification & correction of the </li></ul><ul><ul><ul><li>precipitating cause: </li></ul></ul></ul><ul><ul><ul><li>Precipitating factors </li></ul></ul></ul><ul><ul><ul><li>Drugs! </li></ul></ul></ul><ul><ul><ul><li>Electrolyte imbalance </li></ul></ul></ul><ul><ul><ul><li>– hypokalemia/metabolic alkalosis </li></ul></ul></ul><ul><ul><ul><li>(diuretics, vomiting, diarrhea, infusion) </li></ul></ul></ul><ul><ul><ul><li>GI Bleeding </li></ul></ul></ul><ul><ul><ul><li>Infection </li></ul></ul></ul><ul><ul><ul><li>Constipation </li></ul></ul></ul><ul><ul><ul><li>Large protein meal </li></ul></ul></ul><ul><ul><ul><li>…… . </li></ul></ul></ul>
  23. 26. <ul><ul><ul><li>2. Intervention to reduce the production & </li></ul></ul></ul><ul><ul><ul><li>absorption of gut-derived ammonia & </li></ul></ul></ul><ul><ul><ul><li>other toxins: </li></ul></ul></ul><ul><ul><ul><ul><li>1) Diet: reduce and modify dietary protein </li></ul></ul></ul></ul><ul><ul><ul><li>and maintain Calorie intake </li></ul></ul></ul><ul><ul><ul><ul><li>2) Enemas (mild acid) and/or purgation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>3) Lactulose or lactitol </li></ul></ul></ul></ul><ul><ul><ul><ul><li>4) Inhibition of gut bacteria: </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Antibiotics: neomycin(oral), </li></ul></ul></ul></ul><ul><ul><ul><ul><li>metronidazone? </li></ul></ul></ul></ul><ul><ul><ul><ul><li>5) Modification of colonic flora: probiotics? </li></ul></ul></ul></ul>
  24. 27. Modify colonic flora, resulting in displacement of urease-containing bacteria with lactobacillus Cathartic effect Lower the colonic pH, resulting in the formation of nonabsorbable NH 4 from NH 3 in the colon
  25. 28. <ul><ul><ul><li>3. Stimulation of metabolic </li></ul></ul></ul><ul><ul><ul><li>ammonia metabolism: </li></ul></ul></ul><ul><ul><ul><li>1) Ornithine-aspartate : enhancing the metabolism of ammonia to glutamine </li></ul></ul></ul><ul><ul><ul><li>2) Sodium glutamate or potassium glutamate, Arginine? </li></ul></ul></ul><ul><ul><ul><li>3) Sodium benzoate(oral): acting with glycine in the colon to form hippurate which can be excreted in the urine </li></ul></ul></ul><ul><ul><ul><ul><li>- applied in chronic HE, particularly in those with elevated blood ammonia </li></ul></ul></ul></ul>
  26. 29. <ul><li>4. Correct amino acid metabolic imbalance: </li></ul><ul><li>infusion or oral administration of BCAA </li></ul><ul><li>(branched-chain amino acid) </li></ul><ul><li>5. GABA/BZ complex antagonist: </li></ul><ul><li>flumazenil ( particularly if patient has been given banzodiazepines ) </li></ul><ul><li>6. Other drugs </li></ul>
  27. 31. <ul><ul><ul><li>7. Miscellaneous treatment </li></ul></ul></ul><ul><ul><ul><ul><li>Prevention and treatment of cerebral edema </li></ul></ul></ul></ul>
  28. 32. <ul><li>8. Temporary hepatic support </li></ul><ul><li>9. Liver transplantation </li></ul>
  29. 33. PROGNOSIS <ul><li>Acute hepatic failure (+++) </li></ul><ul><li>Cirrhosis - with precipitant (++) </li></ul><ul><li>Cirrhosis - portal-systemic shunt (+) </li></ul><ul><li>Cirrhosis - end stage (++++) </li></ul>

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