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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.

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Presentation on theme: "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."— Presentation transcript:

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 NH 3 Am. J Clin. Nutr. 26, , 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, , 1973

5 The Krebs-Henseleit cycle A amino acid deamination or deamidation B and C amino acids transamination CO 2 +NH 3 Carbomyl phosphate Aspartic acid citrulline ornithine Arginino- succinic acid arginine urea Am. J Clin. Nutr. 26, , 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

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

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 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

13 Poorly absorbed Disaccharides and soluble fiber 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 Lactulose, Lactitol, Lactose 作用機轉

14 Poorly absorbed Disaccharides and soluble fiber 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 可溶性纖維 果膠 Soluble Fiber, Pectin

15 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 MPSTVPDF MPST BASAL WEEKS 0246 Uribe; Gastroenterology 1985;88:901-7

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 Uribe; Gastroenterology 1985;88:901-7

17 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 Weber; Gastroenterology 1985;89: Stool componentsNitrogen intake and excretion

18 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:

19 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:

20 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

21 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

22 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

23 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

24 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, , 1991

25 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

26 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 –B 12 store decrease –Vitamin B 6 do not accurately reflect body body store –low total serum folate levels due to hypoalbuminemia

27 鋅 Zinc Trace 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

28 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

29 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)

30 Chromium - Glucose tolerance factor Trace 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

31 營養治療方式 Specific nutritional treatment modalities Gabuzda; Am.J Clin Nutr 23: ,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

32 營養對肝病患者之利益 Nutritional Benefit in liver disease patients McCullough; Seminars in Liver Disease Vol 11 no


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