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飲食與肝性腦病變

飲食與肝性腦病變. 膳食蛋白質與 ammonia 蛋白質的變化性 腸道氨的產生 膳食上非氨之影響因素 熱量 : 氮 比值 與油脂 Poorly absorbed disaccharides 與可溶性纖維 Free fatty acids Tryptophan and serotonin GABA and other Neuroactive substances. 龐振宜 藥師. 肝性腦病變的病理因素. Ammonia 的神經毒性 多重協同性 neurotoxins 虛擬 神經傳導物質 / 血漿氨基酸不平衡 GABA 神經過度傳導

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飲食與肝性腦病變

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  1. 飲食與肝性腦病變 • 膳食蛋白質與 ammonia • 蛋白質的變化性 • 腸道氨的產生 • 膳食上非氨之影響因素 • 熱量:氮 比值 與油脂 • Poorly absorbed disaccharides 與可溶性纖維 • Free fatty acids • Tryptophan and serotonin • GABA and other Neuroactive substances 龐振宜 藥師

  2. 肝性腦病變的病理因素 • Ammonia 的神經毒性 • 多重協同性neurotoxins • 虛擬神經傳導物質/血漿氨基酸不平衡 • GABA神經過度傳導 • Banzodiazepine augmentation of GABAergic neurotransmission

  3. Substances tested for effect on blood NH3 Am. J Clin. Nutr. 26, 916-925, 1973

  4. Principal reaction in degradation of Amino Acids produces NH3 Glycine glyoxylic acid + NH3 Serine pyruvic acid + NH3 Threonine -Ketobutyric acid + NH3 Glutamine glutamic acid + NH3 Histidine urocanic acid Phenylalanine + oxaloacetic acid phenylpyruvic acid + aspartic acid Valine + -ketoglutaric acid -ketoglutaric acid + aspartic acid Tryptophan N-formylkynurenine alanine + kynurenine Proline -pyrroline-5-carboxylic acid glutamic semialdehyde glutamic acid Arginine ornithin + urea Am. J Clin. Nutr. 26, 916-925, 1973

  5. The Krebs-Henseleit cycle A amino acid deamination or deamidation B and C amino acids transamination CO2+NH3 Carbomyl phosphate Aspartic acid citrulline Arginino- succinic acid ornithine arginine urea Am. J Clin. Nutr. 26, 916-925, 1973

  6. 蛋白質的變化性protein variability • 比較酪蛋白含血肉類增加 ammonia 造成 CNS 症狀 Bessman; J. Clin Invest 1958 • Milk and cheese diet 改善心智功能降低 blood ammonia Fenton; Lancet 1966 • Milk rather than meat less HE and survival longer in dogs Condon; Am J. Surg 1971 • 植物性蛋白質較肉類或動物性蛋白質為佳 Rudman;Am. J. Clin Nutr 1973

  7. 膳食蛋白質氨基酸組成Amino Acid residues in Dietary Proteins Am J of Surg. 107-114 1971

  8. Treatment of chronic PSE with vegetable and animal protein Diets Uribe: Dig.Dis and Sci vol 27, 1109-1116

  9. 膳食上非氨之影響因素Factors other than Ammonia production influenced by diet • Potentially adverse effects of aromatic A.A. (phenylanaline, tyrosine, tryptophan) • Beneficial effect of BCAA • the content of methionine and conversion to mercaptans • lactose in “milk protein” diets significant therapeutic effects

  10. 膳食上非氨之影響因素Factors other than Ammonia production influenced by diet • Meat highest conc of AAA • Lowest conc of BCAA • Milk Lowest conc of AAA • Highest conc of BCAA • fish was intermediate • Vegetable protein diets to improve HE is probably not related to the BCAA:AAA Ratio

  11. 植物性與動物性膳食對慢性肝腦病變治療之比較Treatment of chronic PSE with vegetable and animal protein diet Uribe; Dig Dis and Sci Vol 27 No. 12 1982

  12. 植物性與動物性膳食對慢性肝腦病變治療之比較Treatment of chronic PSE with vegetable and animal protein diet Clinical efficacy Uribe; Dig Dis and Sci Vol 27 No. 12 p 1109-1115, 1982

  13. 熱量:氮 比值Calorie : Nitrogen Ratio • Increasing the calorie to nitrogen ratio in the diet increase the utilization of dietary protein • Consumption of carbohydrate inhibit glucagon secretion reduce gluconeogenesis and production of ammonia • High carbohydate:protein ratio favorable impact on ammonia metabolism • Protein meal was supplemented with glucose stimulated the uptake of ammonia by muscle • Hyperglucagonemia cause hyperammonemia

  14. Poorly absorbed Disaccharides and soluble fiber Lactulose, Lactitol, Lactose作用機轉 • Acidic intracolonic environment trap ammonia in its ionized form and permit its evacuation in the stool • fermentable carbohydrate source to the bacteria flora alter their metabolism of nitrogen and increase nitrogen incorporation into intestine bacteria • metabolizable dietary fiber increase fecal nitrogen excretion be found in the increased bacterial fraction of stool • caused an average of 3.5 gm less nitrogen to enter the portal system

  15. Poorly absorbed Disaccharides and soluble fiber 可溶性纖維 果膠 Soluble Fiber, Pectin • no acidification of stool • Increased fecal excretion of nitrogen that was primary contained in the bacterial fraction of stool • inhibit ureolysis within colon cause reduction of the urea production rate

  16. 植物性膳食併用車前草纖維Psyllium Plantago對肝性腦病變與糖尿病的利益 MPST VPDF BASAL VPDF MPST WEEKS 0 2 4 6 Uribe; Gastroenterology 1985;88:901-7

  17. 植物性膳食併用車前草纖維Psyllium Plantago對肝性腦病變與糖尿病的利益 Uribe; Gastroenterology 1985;88:901-7

  18. 植物性膳食對肝硬化患者的氮代謝Effects of vegetable Diets on nitrogen metabolism in cirrhotic subjects Stool components Nitrogen intake and excretion Weber; Gastroenterology 1985;89:538-44

  19. 植物性與動物性膳食對伴有腦病變之慢性肝硬化比較植物性與動物性膳食對伴有腦病變之慢性肝硬化比較 Bianchi; J. Internal Medicine 1993;233:385-392

  20. 植物性與動物性膳食對伴有腦病變之慢性肝硬化比較植物性與動物性膳食對伴有腦病變之慢性肝硬化比較 Bianchi; J. Internal Medicine 1993;233:385-392

  21. 植物性膳食的問題The problem of vegetable protein diet • Patient compliance • Palatability • Easy satiety • Anorexia, unable to ingest sufficient amount of vegetable to bring their protein intake g/kg body weight • High-fiber diet Reduced the absorption of calcium, zinc, and magnesium minerals • Limited the clinical feasibility of treatment

  22. Tryptophan and Serotonin • Normal diet contain approximately 1 g/day of tryptophan • easily traverses the BBB • increased brain uptake of tryptophan is associated with increased serotonin turnover in the brain • High carbohydrate diet compete with tryptophan for albumin binding sites • BCAA enriched formulations competition between BCAA and free AAA for entry across the BBB

  23. 肝病營養不良Liver disease malnutrition • Muscle Wasting • significantly less ammonia uptake and had higher brain uptake of ammonia • Protein Metabolism • Abnormal BCAA:AAA ratio enhance catabolism or decrease anabolism • Zinc • Poor dietary intake, reduced intestinal absorption and increased urinary loss • influence multiple aspects of ammonia mechanism • derangement of brain neurotransmitter metabolism

  24. 肝病營養評估Assessment of nutritional status in liver disease • Low levels of circulating protein (plasma albumin) • muscle mass and subcutaneous fat stores (triceps and subscapular skinfold, midarm muscle circumference) • visceral protein stores (albumin, transferrin, prealbumin, retinol binding protein) • creatinine-height index • immune status • nitrogen balance, blood urea nitrogen, serum alpha-amino nitrogen, and plasma amino acids

  25. 肝病營養不良之病因Etiology of malnutrition in patients with liver disease Munoz; Seminars in liver Disease vol 11 No.4, 278-291, 1991

  26. 肝病營養不良之重要因素Potential Causes of Malnutrition in Liver Disease • Decreased quality and quantity of food • Disease related • Anorexia, nausea and vomiting • Iatrogenic • Hospitalization related • Unpalatable diets • Purgation and neomycin enteropathy • Impaired nutrition digestion and absorption • Pancreatic and bile salt deficiency • Enteropathy • Increased energy requirements • Energy cost of alcohol metabolism • Stressful complications • Accelerated protein breakdown • Protein Oxidation • Inefficient protein synthesis

  27. 肝病微量營養素缺乏Micronutrients deficiency in liver disease • Fat-soluble vitamins • low vitamin A serum levels • vitamin D deficiency • hyperlipidemia despite subnormal vitamin E store • prolong the prothrombin time in the absence of true vitamin K deficiency • Water soluble vitamins • B12 store decrease • Vitamin B6 do not accurately reflect body body store • low total serum folate levels due to hypoalbuminemia

  28. 鋅 ZincTrace Metals In liver disease • Stress hormones and cytokines elevated depressing absorption • 70% loosely bound to albumin influence bioavailability and tissue distribution of zinc • Depress in white blood cells, pancreatic juice, liver and testes

  29. 鋅 缺乏表徵Functional consequences of Zinc deficiency • Neurosensory defects • Cognitive dysfunction • Impaired night vision, retina function, and macular degeneration • Depressed appetite and taste sensation • Skin lesions • Hypogonadism • Immune dysfunction • Altered protein metabolism and depressed wound healing • Worse hepatic encephalopathy through increasing ammonia levels

  30. 硒 Selenium Trace Metals In liver disease • Decreased by 17% in non cirrhotics and by 48% in cirrhotic alcoholics • 43% of the patients with primary biliary cirrhosis below the control range Major function is its contribution to oxidant defenses (glutathione peroxidase and selenoprotein P)

  31. Chromium - Glucose tolerance factorTrace Metals In liver disease • Peripheral insulin resistance and glucose intolerance is seen in a variety of types of liver disease • Increased loss observed after a variety of stress and trauma states • Cause a syndrome of hyperglycemia, peripheral insulin resistance, glucose intolerance, and neuropathy

  32. 營養治療方式Specific nutritional treatment modalities Gabuzda; Am.J Clin Nutr 23:479-487,1970 • Low protein diet • reduce renal plasma flow and glomerular filtration • beta-adrenergic blockade accelerates protein oxidation • decrease plasma catecholamines • increasing protein requirement • adversely affecting glucagon metabolism and • hepatic metabolic activity

  33. 營養對肝病患者之利益Nutritional Benefit in liver disease patients McCullough; Seminars in Liver Disease Vol 11 no.4 265-77 1991

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