Hepatic encephalopathy/ Portal-systemic encephalopathy /hepatic coma Hepatic encephalopathy is a neuropsychiatric syndrome caused by hepatic insufficiency It represents a reversible decrease in neurologic function, based upon the disorder of metabolism which are caused by severe decompensated liver disease “Portal-systemic encephalopathy” - patients with portal hypertension abnormal shunting of blood It occurs most often in patients with cirrhosis but also occur in acute hepatic failure.

Causes: Chronic parenchymal liver disease: Chronic hepatitis: Cirrhosis.  Fulminating hepatic failure: Acute viral hepatitis Drugs Toxins e.g. Wilson’s Disease, CCL4, Surgical Portal-systemic anastomoses, - portacaval shunts, or Transjugular intrahepatic portal-systemic shunting [TIPS]).

Factors precipitating hepatic encephalopathy: Metabolic stress Infection Electrolyte imbalance, especially hypokalemia; Dehydration , Renal failure Diuretic drugs, Disorders that increase gut protein GI bleeding High-protein diet Nonspecific cerebral depressants alcohol, sedatives, analgesics

Pathogenesis Absorbed products – detoxified in Liver PSS – toxic substances enter systemic circulation - Which are toxic to brain Other factors Increase sensitivity to GABA (inhibitory neurotransmitter) Increase circulating levels of endogenous benzodiazepines

Pathogenesis (acute & chronic ) The basic cause is same in both forms but the mechanism is somewhat different Diminished detoxification of toxic intestinal nitrogenous compounds Increased in blood NH3 etc Toxic effect on brain Appearance of abnormal amines in systemic circulation Interference with neurotransmission Dr S Chakradhar

Endotoxins of HE Ammonia Mercaptans - degradation of methionine in the gut Phenols Free fatty acids

Ammonia Production Small intestine: degradation of glutamine produced NH3 Large intestine: Breakdown of Urea and proteins by normal flora Muscles: proportion to muscle work Kidney: increased production when hypokalemia and diuretic therapy Liver: detoxified ammonia into urea Brain can also detoxified ammonia into glutamine

Clinical Features of hepatic encephalopathy: A Disturbance in consciousness Disturbances in sleep rhythm. Impaired memory/ apraxia Mental confusion. Apathy. Drowsiness / Somnolence  Coma.

B. Changes Personality Childish behavior. May be aggressive out burst. Euphoric. Foetor hepaticus – Foul–smelling breath associated with liver disease due to mercaptans

C Neurological signs: Flapping tremor / Asterixis (in pre coma). Exaggerated tendon reflex. Extensor plantar reflex.

Clinical stages of hepatic Encephalopathy

Investigations Diagnosis is usually made clinically No Pathognomonic liver function abnormality Elevation of blood ammonia Hypokalaemia EEG (Electroencephalogram) CSF & CT Scan – Normal Other Routine Investigations - TC, DC, ESR, Hb, Na, k, Urea, Creatinine, Prothrombin time

Differential Diagnosis Subdural Haematoma Drug or Alcohol intoxication Wernicke’s encephalopathy Hypoglycaemia

Treatment Hospitalization is mandatory ABC maintain Remove the cause & precipitating factors IV fluid dextrose saline & Inj. Thiamine Maintenance of fluid, electrolytes & calorie Diet – Restriction of protein diet High glucose diet Avoid constipation – Lactulose 15-20ml X 3 times a day Antibiotics : Neomycin Ampicillin Metronidazole Inj. Vitamin K

Mechanism of action of Lactulose: Osmotic laxative effect. It reduces pH of colonic content & thereby prevents absorption of NH3. Incorporates nitrogen into bacteria