严重肝病引起以代谢紊乱为基础神经福建肝病医院

Hepatic Encephalopathy 福州白湖亭医院肝病科,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,Definition (2),Subclinical or latent HE diagnosed only by precise mental tests or EEG, no obvious clinical and biochemical abnormalities,Incidence/prevalence,Universal feature of acute liver failure 50%70% in chronic hepatic failure Difficult to estimate,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,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,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,Pathogenesis (2),Postulated factors/mechanisms: Ammonnia neurotoxicity Synergistic neurotoxins Excitatory inhibitory neurotransmitters and plasma amino acid imbalance hypothesis -Aminobutyric acid（GABA）/BZ hypothesis,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,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,Synergistic neurotoxins,Ammonia Mercaptans (硫醇) Short-chain fatty acids,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,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,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,- 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,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,Clinical manifestation,Clinically, HE manifests diverse signs and symptoms. Early forms, quite subtle changes in personality or level of performance. As HE advances, a disturbance of consciousness, impaired intellectual function, neuromuscular abnormalities, mood changes, inversion of the sleep cycle, and slowed reaction time. Day-night reversal is often an early manifestation.,Clinical manifestation,Criteria for clinical stages Personality and mental changes Asterixis Abnormal EEG patterns,Clinical Grading of HE,Clinical Grading of HE,Laboratory and other tests,Serum ammonia Elevation of serum ammonia: 60%80% particularly in chronic HE (with portosystemic shunting) Electroencephalogram (EEG) Severe slowing with frequencies in the theta and delta Evoked potentials Variation, lack of specificity and sensitivity,Reitan trail-making test,Psychometric tests -Number connection test,Writing chart,Psychometric tests -Digit symbol test,Diagnosis and differential diagnosis,Diagnosis,Patients with severe liver disease and/or portal hypertension, portosystemic shunting Mental changes: confusion, somnolence, coma Factors precipitating or aggravating HE exist Severely impaired liver function and/or hyperammonemia Flapping tremor and typical EEG changes,Diagnosis,Recognition of the latent and/or subcli