Hepatic encephalopathy Portalsystemic encephalopathy hepatic coma 1 Hepatic

Hepatic encephalopathy/ Portal-systemic encephalopathy /hepatic coma 1. Hepatic encephalopathy is a neuropsychiatric syndrome caused by hepatic insufficiency 2. It represents a reversible decrease in neurologic function, based upon the disorder of metabolism which are caused by severe decompensated liver disease 3. “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: l Chronic parenchymal liver disease: l Chronic hepatitis: l Cirrhosis. l Fulminating hepatic failure: l Acute viral hepatitis l Drugs l Toxins e. g. Wilson’s Disease, CCL 4, Surgical Portal-systemic anastomoses, - portacaval shunts, or Transjugular intrahepatic portal-systemic shunting [TIPS]).

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

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

Pathogenesis (acute & chronic ) l The basic cause is same in both forms but the mechanism is somewhat different l Diminished detoxification of toxic intestinal nitrogenous compounds Increased in blood NH 3 etc Toxic effect on brain Appearance of abnormal amines in systemic circulation Interference with neurotransmission Dr S Chakradhar 5

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

Ammonia Production l Small intestine: degradation of glutamine produced NH 3 l Large intestine: Breakdown of Urea and proteins by normal flora l Muscles: proportion to muscle work l Kidney: increased production when hypokalemia and diuretic therapy l Liver: detoxified ammonia into urea l Brain can also detoxified ammonia into glutamine

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

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

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

l Clinical stages of hepatic Encephalopathy

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

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

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

Mechanism of action of Lactulose: l Osmotic laxative effect. l It reduces p. H of colonic content & thereby prevents absorption of NH 3. l Incorporates nitrogen into bacteria