精品论文严重肝病引起的以代谢紊乱为基础的神经课件

Hepatic Encephalopathy 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 1 Universal feature of acute liver failure 1 50%70% in chronic hepatic failure 1 Difficult to estimate Etiology 1Fulminant hepatic failure acute severe viral hepatitis, drug/toxin, acute fatty liver of pregnancy Due to acute hepatocellular necrosis 1Chronic 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) 4 Toxic materials derived from nitrogeneous substrate in the gut and bypass the liver 4 HE is caused by several factors act synergistically 4 Several putative gut-derived toxins identified Pathogenesis (2) Postulated factors/mechanisms: 1 Ammonnia neurotoxicity 1 Synergistic neurotoxins 1 Excitatory inhibitory neurotransmitters and plasma amino acid imbalance hypothesis 1 -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 v Elevation of ammonia: detected in 60%80% v Absolute concentration of ammonia, ammonia metabolites in blood or cerebrospinal fluids, correlates only roughly with the presence or severity of HE v Few cases: within normal range Synergistic neurotoxins v Ammonia v Mercaptans (硫醇) v 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 4 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 4 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: 3 More AAAs enter into blood-brain barrier and CNS 3 Decreased synthesis of normal neurotransmitters 3Enhanced 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): 2 Principal inhibitory neurotransmitters 2 Generated in the gut by bacteria 2 Bypasses the diseased or shunted liver 2Increased blood-brain barrier permeability Pathohistology 1 Brain may be normal or cerebral edema Particularly in fulminant heptic failure Cerebral edema is likely the secondly changes 1 In patients with chronic liver disease Astrocytes: increase in number and enlargement 1 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 v Personality and mental changes v Asterixis v Abnormal EEG patterns Clinical Grading of HE GradeSymptomsSignEEG Abnormalities I-ProdromeAltered sleep patterns Fluctuating mood- euphoria,depression Inappropriate behavior Apathy Loss of affect Writing difficult Constructional apraxia Asterixis may be present May be present II-Mild HEMild confusion Disorientation Drowsiness（嗜睡） Asterixis(easily elicitated) Ataxia（共济失调 ） Fetor hepaticus肝臭 Abnormal Slower rhythms Clinical Grading of HE GradeSymptomsSignEEG Abnormalities III- Moderate HE Marked confusion Arousable from sleep Responsive Asterixis Rigidity of limbs Hyperflexia Clonus Grasping and sucking reflexes Babinski Moderate IV-ComaUnconsciousness Unresponsive to stimuli Flaccid limbs Diminished reflexes No muscle tone significant Laboratory and other tests v Serum ammonia Elevation of serum ammonia: 60%80% particularly in chronic HE (with portosystemic shunting) v Electroencephalogram (EEG) Severe slowing with frequencies in the theta and delta v 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 4 Patients with severe liver disease and/or portal hypertension, portosystemic shunting 4 Mental changes: confusion, somnolence, coma 4 Factors precipitating or aggravating HE exist 4 Severely impaired liver function and/or hyperammonemia 4 Flapping tremor and typical EEG changes Diagnosis + Recognition of the latent and/or subclinical HE Important for view of the prevalence of cirrhosis + In the absence of characteristic features Abnormal neuropsychiatric function: Number connection test Digit symbol tests Block design Visual reaction times Differential diagnosis 4 Hypoglycemia（低血糖） 4 Uremia 4 Diabetic ketoacidosis（糖尿病酮症酸中毒） 4 Nonketotic hyperosmolar syndrome（非酮症高渗综合症 ） 4 Subdural hematoma（硬膜下血肿） 4 Cerebrospinal infection （脑脊髓感染） Treatment The goals of therapy vTo treat the underlying liver disease and improve mental. vThe most important initial aspects of care are to diagnose the condition properly, exclude other causes of encephalopathy, and search for precipitating factors 一、Identification and treatment of precipitating factors vThese precipitating events may be readily apparent or subtle. Therefore, detailed discussions and a careful assessment of changes in laboratory values are necessary. vSupportive care Correction of fluid, electrolyte, glucose, acid-alkaline abnormalities Management of cerebral edema, bacteremia 二、Decreasing nitrogen load and ammonia productions and absorption of enteric toxins 4Decreasing ammonia productions 3Dietary protein restriction 3Bowel cleaning(clysis 灌肠, catharsis 导泻) 3Nonabsorbable disaccharides 3 Antibiotics 3eradication of Hp 4Increasing ammonia metabolisms Dietary protein restriction lRestriction of dietary protein at the time of acute HE with subsequent increments to assess clinical tolerance is a classic cornerstone of therapy lProtein restriction: 0.81.0g/kg.d l Vegetable and dairy sources are preferable to animal protein lA positive nitrogen balance positive efects Bowel cleaning l Clysis l Laxative (e.g. magnesium citrate 硫酸镁) Notes: all enemas must be neutral or acidic to reduce ammonia absorption Nonabsorbable disaccharides Lactulose （乳果糖） l Synthetic disaccharide l First-line pharmacological treatment l Release lactic and acetic acids by colonic bacteria l Decreasing stool pH to about 5.5 l Reduce portion of ammonia and its absorption l Effective in 80% of patients l Cause 23 soft stool/d Antibiotics lNeomycin（新霉素）: 24g/D Litter is absorbed Impaired hearing or deafness ( long term use) Long term use (1 month) is not advisable l Metronidozol（甲硝唑）: 0.2g qid as effective as neomycin l Rifaximin