1 / 37

Hepatic encephalopathy

Hepatic encephalopathy. a potentially-reversible neuropsychiatric abnormality in the setting of liver failure, whether chronic (as in cirrhosis), or acute. Section 1 Hepatic insufficiency. Etiology of Hepatic failure. 1. biological 2. physical and chemical 3. inherital(congenital)

darcyc
Download Presentation

Hepatic encephalopathy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Hepatic encephalopathy a potentially-reversible neuropsychiatric abnormality in the setting of liver failure, whether chronic (as in cirrhosis), or acute

  2. Section 1 Hepatic insufficiency

  3. Etiology of Hepatic failure 1. biological 2. physical and chemical 3. inherital(congenital) 4. immunol 5. nutritional

  4. Hepatic function & dysfunctions 1. metabolism: 2. secreting & excreting: 3. detoxication & defense 4. coagulation 5. affecting other organ hepatic encephalophcy

  5. Clinical Manifestations of Cirrhosis

  6. Impact of Hepatic Encephalopathy on survival in 1402 cirrhotic patients

  7. Section 2 hepatic encephalopathy a potentially-reversible neuropsychiatric abnormality in the setting of liver failure

  8. Part 1 Etiology and classification of HE

  9. Major types of hepatic encephalophcy ①Acute fulminant type: hepatic necrosis ②Chronic recurrent type: cirrhosis Type A (=acute) : HE associated with ALF Type B (=bypass): portal-systemic shunting without associated intrinsic liver disease Type C (=cirrhosis): cirrhosis 1998 in Vienna,

  10. Clinical presentation Coma Drowsiness Confusion Sleeping disorder Apathy Childishness Hepatic coma = HE？

  11. Chronic hepatic encephalopathy ①prodromal ~: mood & behavior ②precoma ~: drowsy, asterixis ③stuporous ~: speaking and obeying simple commands ④coma ~: no response to painful stimuli

  12. Part 2 pathogenesis of HE

  13. Pathogenesis Multifarious toxins → Dysfunction of CNS (No obvious morphological change) Several hypotheses to uncover the mystery

  14. 1. NH3 intoxication Normal: plasma NH3 < 100μg％ 80~90％ of patient: ↑2~3 folds (200~500 μg％）

  15. Blood NH3 configuration • NH3 NH4+ • 2% 98% pH  pH

  16. (1) NH3 increased in HE

  17. Clearing Generation Urea syntheses↓ Intestinal NH3↑ liver Blood NH3↑ Via collateral↑ Renal backflow NH3↑ Muscle production↑ Syntheses with NH3↓ The reasons of NH3↑

  18. UREOGENESIS AMMONIA Aspartic acid Citrulline UREA CYCLE Ornithine Arginine Ureogenesis takes place in the liver and is essential for ammonia detoxification UREA

  19. (2) NH3 toxicity on CNS NH3↑interferes with ① cerebrocellular energy: ？ ② neurotransmitter imbalance ③ neurocellular membrane ion transferring

  20. Glucose choline NADH NAD+ ⑥ AcetylCoA acetylcholine Pyruvate Lactic acid ⑥ Oxaloacetat CoA ⑦ Citrate ⑥ Succinate NADH NAD+ ① α-ketoglutatrate GABA ⑦ NADH NH3 ② ATP ADP NAD+ ③ Glutamate Glutamine ④ ⑤ NH3 Energy metabolism & Neurotransmitter in HE

  21. Balance of exiting & inhibition

  22. Mercaptan(metheonine) NH3 Indole(tryptophan) Phenol(tyrosine, tyramine) monoamine Short chain fatty acid Synergistic effect of neurotoxin neurotoxin cerebral energy cerebral cell respiration Na+ pump neural impulse delivery synapse intoxication decayed products of enteric bacteria

  23. 2. False neurotransmitter(FNT) & plasma amino acid imbalance Serious liver disease， BCAA/AAA ratio ↓ < 1( Nor > 3 ) → ? CNS disorder BCAA: branchchainamino acid AAA：aromatic amino acid leucine, isoleucine, and valine / Tryptophan, Tyrosine , phenylalanine

  24. Liver deactivation↓ uptake & utilizing BCAA↑in tissue insulin↑ glucagon ↑ Protein decomposed↑ in muscle & liver Blood NH3↑ glyconeogenesis↓ AAA↑ (1) Causes of plasma amino acid imbalance

  25. (2) FNT formation phenylalanine Tyrosine phenylalamine tyramine MAO decarboxylation  ? in liver BBB in brain Tyrosine hydrogenase β- hydrogenase dopa β -phenylethanolamine、 octpamine ↑ （FNT） NE dopamine

  26. CHOHCH2NH2 HO CHOHCH2NH2 HO phenylethanolamine noradrenaline HO CHCH2NH2 CHOHCH2NH2 HO HO octopamine dopamine Comparison between TNT and FNT

  27. NT ARAS maintains consciousness through NT

  28. AAA ↑ BCAA tryptophan ↑ (3) plasma amino acid imbalance and FNT formation glutamine antiport FNT ? tryptamine 5-HT blood BBB

  29. 3. GABA alteration and HE 1. GABA↑: Originated from gut and brain 2. Affinity of GABA to its receptor ↑ 3. Synergistic allosteric effect of other:

  30. transferaminase decarboxygenase succinic acid semialdehyde GABA Glutamatic acid － + NH3 ↑ NH3↑ early stage late stage GABA alteration

  31. 4. Comprehensive view BloodBrain Intestine GABA ↑ → GABA↑ ATP↓ NH3 ↑ → GA↓, Ach↓ ↓ Glutamine↑ Glucagon→ AAA↑ → AAA↑→FNT Insulin → BCAA↓

  32. Part 3 Precipitating factors 1. Toxins produced in intestine↑ 2. Permeability of blood – brain barrier↑ 3. Increased sensitivity of brain to toxins by hypoxia, fluid and electrolytes abnormalities, infection, hypnotics etc

  33. Part 4 Principle of prevent & treatment (1) protect hepatic cell (2) decrease NH3 : benzoate, lactulose (3) restore plasma amino acid balance (4) increase normal neurotransmitter

  34. What are they doing?

  35. Thanks!

More Related