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HEPATIC ENCEPHALOPATHY Dr. Bindu Mohandas M-5 unit SYNONYMS Portosystemic encephalophathy Hepatic coma Incidence: 71% in cirrhosis DEFINITION Hepatic Encephalopathy is a neuropsychatric syndrome caused by liver disease, characterised by disturbances in conciousness level & behaviour, personality changes, fluctuating neurological signs, asterixis & distinctive EEG changes. TYPES Acute/ Subacute Reversible Chronic Progressive leading to irreversible coma & death Factors Precipitating hepatic encephalopathy Increased Protein Load (nitrogen) – GI bleeding, excessive dietary protein, uremia, constipation Drugs – Sedatives, Antidepressants Dehydration – Diuretics, paracentesis Trauma – including surgery Electrolyte imbalance – hypokalemia, alkalosis, hypovolemia Large binge of alcohol ETIOPATHOGENESIS Abnormality in nitrogen metabolism by urease producing bacteria in bowel. Accumulation of ammonia, octapamine aminoacid, fatty acid, mercaptans. Carried to liver by portal circulation. Fail to get detoxified due to hepatocellular disease/ Porto systemic shunting of blood. Enters the systemic circulation. Crosses the blood brain barrier. Accumulates in brain. Ammonia induced alteration in astrocyte glutamine & glutamate concentrations. Altered neurotransmission & cerebral oedema. CLINICAL FEATURES Apathy, inability to concentrate, confusion, disorientation, drowsiness, slurring of speech derangement of conciousness Altered sleep rhythm Increased psychomotor activity Progressive drowsiness, stupor & coma Focal / generalised seizures Exaggeration of DTR Asterixis Constructional aparaxia Fetor hepaticus Inability to perform simple arithmatic tasks & change in handwriting. Clinical grading of hepatic encephalopathy Stage Mental Status Grade I Poor conc, slurred speech, mild confusion disordered sleep rhythm Grade II Asterixis EEG +/- Usually normal Drowsy but arousable, lethargic, moderate confusion + Abnorm al Grade III Marked confusion, sleepy but responds to pain & voice + Abnorm al Grade IV Coma- unconscious, non responsive - Abnorm al INVESTIGATIONS EEG – Shows high voltage, slow wave forms reduced alpha rhythm & increased delta activity. Elevation of serum ammonia No pathognomonic liver function abnormality CT Brain & CSF analysis – Normal USG Abdomen MRI scan in stage IV shows cerebral oedema MANAGEMENT Treat/Remove the precipitating causes Dietary protein restriction Lactulose (15-30ml 8th hourly) or Lactitol Neomycin (1-4g 4-6 hourly) or Ampicillin i.v mannitol Avoid drugs – sedatives, diuretics Liver transplantation – defenite Rx The use of levodopa, bromocriptine, ketoanalogues of aminoacid & i-v infusion of aminoacids, haemoperfusion – role is unclear. PROGNOSIS * Hepatic encephalopathy is associated with short survival in cirrhotic patients * Factors worsening the prognosis are 1. male sex 2. Increased levels of S. bilirubin, alkaline phosphatase, Potassium, BUN 3. Reduced albumin and prothrombin activity. DIFFERENTIAL DIAGNOSIS Subdural haematoma Drug or alcohol intoxication Delirium tremens Wernicke’s encephalopathy Primary psychiatric disorders Hypoglycemia Neurological Wilson’s disease SOURCE OF INFORMATION www.google.com www.pubmed.com Harrison’s internal medicine Davidson’s Principle of Medicine Alagappan’s practical manual T H A N K Y O U