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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/14,*,单击此处编辑母版文本样式,第二级,单击此处编辑母版标题样式,2020/11/14,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/14,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/14,*,严重肝病引起以代谢紊乱为基础神经福建肝病医院,严重肝病引起以代谢紊乱为基础神经福建肝病医院严重肝病引起以代谢紊乱为基础神经福建肝病医院Definition(1)Hepatic encephalopathy(HE),It represents a reversible decrease in neurological function,based upon the disorder of metabolism which is caused by severe decompensated liver disease.,严重肝病引起的以代谢紊乱为基础的神经、精神综合征。主要临床表现为意识障碍、行为失常和昏迷2020/11/142,严重肝病引起以代谢紊乱为基础神经福建肝病医院严重肝病引起以代,Definition(1),Hepatic encephalopathy(HE),It represents a reversible decrease in neurological function,based upon the disorder of metabolism which is caused by severe decompensated liver disease.,严重肝病引起的以代谢紊乱为基础的神经、精神综合征。主要临床表现为意识障碍、行为失常和昏迷,2020/11/14,2,Definition(1)Hepatic enceph,Definition(2),Subclinical or latent HE,diagnosed only by precise mental tests or EEG,no obvious clinical and biochemical abnormalities,2020/11/14,3,Definition(2)Subclinical or l,Incidence/prevalence,Universal feature of acute liver failure,50%70%in chronic hepatic failure,Difficult to estimate,2020/11/14,4,Incidence/prevalence 2020/11/1,Etiology,Fulminant hepatic failure,acute severe viral hepatitis,drug/toxin,acute fatty liver of pregnancy,Due to acute hepatocellular necrosis,Chronic liver disease,cirrhosis of all types,surgically induced portal-systemic shunts,primary liver cancer,Due to one or more potentially reversible precipitating factors,2020/11/14,5,Etiology Fulminant hepatic fai,Common precipitating factor,Deterioration in hepatic function,Drugs,Sedatives,potentially hepatotoxic,agents,Gastrointestinal bleeding,Excessive dietary protein,Uremia/azotemia,Infection,Constipation,Anesthesia and surgery,Hypoxia,Diuretics,hypokalemia,Alkalosis,hypovolemia,Nitrogenous,Encephalopathy,Non-Nitrogenous,Encephalopathy,2020/11/14,6,Common precipitating factorDet,2020/11/14,7,2020/11/147,Pathogenesis(1),Toxic materials derived from nitrogeneous substrate in the gut and bypass the liver,HE is caused by several factors act synergistically,Several putative gut-derived toxins identified,2020/11/14,8,Pathogenesis(1)Toxic materia,Pathogenesis(2),Postulated factors/mechanisms:,Ammonnia neurotoxicity,Synergistic neurotoxins,Excitatory inhibitory neurotransmitters and plasma amino acid imbalance hypothesis,-Aminobutyric acid（GABA）/BZ hypothesis,2020/11/14,9,Pathogenesis(2)Postulated fac,2020/11/14,10,2020/11/1410,Ammonia neurotoxicity,Over production and/or hypoeccrisis,Poor hepato-cellular function:incomplete metabolism,Portal-systemic encephalopathy:bypass,Ammonia intoxication,Interfere with cerebral metabolism:,Depletion of glutamic acid,aspartic acid and ATP,Depression cerebral blood flow and oxygen,consumption,2020/11/14,11,Ammonia neurotoxicity Over pro,Ammonia neurotoxicity,Elevation of ammonia:detected in 60%80%,Absolute concentration of ammonia,ammonia metabolites in blood or cerebrospinal fluids,correlates only roughly with the presence or severity of HE,Few cases:within normal range,2020/11/14,12,Ammonia neurotoxicity Elevatio,Synergistic neurotoxins,Ammonia,Mercaptans,(硫醇),Short-chain fatty acids,2020/11/14,13,Synergistic neurotoxins Ammoni,Excitatory inhibitory neurotransmitter&plasma amino acids imbalance,Neurotransmission:,Mediated by both excitatory and inhibitory neurotransmitters,Their synthesis controlled by brain concentration of the precursor amino acids,2020/11/14,14,Excitatory inhibitory neurotra,Increased aromatic amino acids(AAAs),Tyrosine,（酪氨酸）,Phenylalanine,（苯丙氨酸）,Tryptophan,（色氨酸,Due to the failure of hepatic deamination,Decreased branched-chain amino acids(BCAAs),Valine,（缬氨酸）,Leucine,（亮氨酸）,Isoleucine,（异亮氨酸）,Due to increased metabolism by skeletal muscle and kidneys or increased insulin,Excitatory inhibitory neurotransmitter&plasma amino acids imbalance,2020/11/14,15,Increased aromatic amino acid,Imbalance of plasma amino acid:,More AAAs enter into blood-brain barrier and CNS,Decreased synthesis of normal neurotransmitters,Enhanced synthesis of false neurotransmitters,Octopamine(苯乙醇胺)Tryptophan(,-羟酪胺),Excitatory inhibitory neurotransmitter&plasma amino acids imbalance,2020/11/14,16,Imbalance of plasma amino acid,-Aminobutyric acid hypothesis,-Aminobutyric acid(GABA):,Principal inhibitory neurotransmitters,Generated in the gut by bacteria,Bypasses the diseased or shunted liver,Increased blood-brain barrier permeability,2020/11/14,17,-Aminobutyric acid hypothesi,2020/11/14,18,2020/11/1418,Pathohistology,Brain may be normal or cerebral edema,Particularly in fulminant heptic failure,Cerebral edema is likely the secondly changes,In patients with chronic liver disease,Astrocytes:increase in number and enlargement,In a very long-standing case,Thin cortex,loss of neurons fibers,laminar,necrosis,pyramidal tracts demyelination,2020/11/14,19,Pathohistology Brain may be no,2020/11/14,20,2020/11/1420,Clinical manifestation,Clinically,HE manifests diverse signs and symptoms.,Early forms,
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