Hepatic encephalopathy/ Portal-systemic encephalopathy /hepatic comaHepatic encephalopathy/ Portal-systemic encephalopathy /hepatic coma

1.1. Hepatic encephalopathy is a neuropsychiatric syndrome caused by hepatic Hepatic encephalopathy is a neuropsychiatric syndrome caused by hepatic insufficiency insufficiency

2.2. It represents a reversible decrease in neurologic function, based upon the disorder It represents a reversible decrease in neurologic function, based upon the disorder of metabolism which are caused by severe decompensated liver diseaseof metabolism which are caused by severe decompensated liver disease

3.3. ““Portal-systemic encephalopathy” - patients with portal hypertension abnormal Portal-systemic encephalopathy” - patients with portal hypertension abnormal shunting of bloodshunting of blood

It occurs most often in patients with cirrhosis butIt occurs most often in patients with cirrhosis but also occur in acute hepatic failure. also occur in acute hepatic failure.

Causes:Causes: Chronic parenchymal liver disease:Chronic parenchymal liver disease:

Chronic hepatitis: Chronic hepatitis: Cirrhosis.Cirrhosis.

  Fulminating hepatic failure:Fulminating hepatic failure:Acute viral hepatitisAcute viral hepatitisDrugsDrugsToxins e.g. Wilson’s Disease, CCLToxins e.g. Wilson’s Disease, CCL44,,

Surgical Portal-systemic anastomoses, - portacaval shunts, or Surgical Portal-systemic anastomoses, - portacaval shunts, or Transjugular intrahepatic portal-systemic shunting [TIPS]).Transjugular intrahepatic portal-systemic shunting [TIPS]).

Factors precipitating hepatic encephalopathy:Factors precipitating hepatic encephalopathy: Metabolic stress Metabolic stress

InfectionInfection Electrolyte imbalance, especially hypokalemia; Electrolyte imbalance, especially hypokalemia; Dehydration , Renal failure Dehydration , Renal failure Diuretic drugs, Diuretic drugs,

Disorders that increase gut protein Disorders that increase gut protein GI bleedingGI bleeding High-protein dietHigh-protein diet

Nonspecific cerebral depressants Nonspecific cerebral depressants alcohol, sedatives, analgesicsalcohol, sedatives, analgesics

PathogenesisPathogenesis Absorbed products – detoxified in Liver Absorbed products – detoxified in Liver PSS – toxic substances enter systemic circulation - Which PSS – toxic substances enter systemic circulation - Which

are toxic to brain are toxic to brain Other factors Other factors Increase sensitivity to GABA (inhibitory neurotransmitter)Increase sensitivity to GABA (inhibitory neurotransmitter) Increase circulating levels of endogenous benzodiazepinesIncrease circulating levels of endogenous benzodiazepines

Pathogenesis (acute & chronic ) Pathogenesis (acute & chronic ) The basic cause is same in both forms but the mechanism is The basic cause is same in both forms but the mechanism is

somewhat different somewhat different

Diminished detoxification of toxic intestinal nitrogenous compounds Diminished detoxification of toxic intestinal nitrogenous compounds

Dr S ChakradharDr S Chakradhar 55

Increased in blood NH3 etc

Toxic effect on brain

Appearance of abnormal amines in systemic circulation

Interference with neurotransmission

Endotoxins of HEEndotoxins of HE AmmoniaAmmonia• Mercaptans - Mercaptans - degradation of methionine in the degradation of methionine in the

gutgut PhenolsPhenols Free fatty acidsFree fatty acids

Ammonia ProductionAmmonia Production Small intestine: Small intestine: degradation of glutaminedegradation of glutamine produced NH3 produced NH3 Large intestine: Breakdown of Urea and proteins by Large intestine: Breakdown of Urea and proteins by normal normal

floraflora Muscles: proportion to muscle workMuscles: proportion to muscle work Kidney: increased production when Kidney: increased production when hypokalemia and diuretic hypokalemia and diuretic

therapytherapy Liver: detoxified ammonia into urea Liver: detoxified ammonia into urea Brain can also detoxified ammonia into glutamineBrain can also detoxified ammonia into glutamine

Clinical Features of hepatic encephalopathyClinical Features of hepatic encephalopathy::

AA Disturbance inDisturbance in consciousnessconsciousness Disturbances in sleep rhythm.Disturbances in sleep rhythm. Impaired memory/ apraxia Impaired memory/ apraxia Mental confusion.Mental confusion. Apathy.Apathy. Drowsiness / Somnolence Drowsiness / Somnolence  Coma.Coma.

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

liver disease due to mercaptans liver disease due to mercaptans

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

Clinical stages of hepatic Encephalopathy Clinical stages of hepatic Encephalopathy

InvestigationsInvestigations

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

Creatinine, Prothrombin timeCreatinine, Prothrombin time

Differential DiagnosisDifferential Diagnosis Subdural HaematomaSubdural Haematoma Drug or Alcohol intoxicationDrug or Alcohol intoxication Wernicke’s encephalopathyWernicke’s encephalopathy HypoglycaemiaHypoglycaemia

TreatmentTreatment Hospitalization is mandatory Hospitalization is mandatory ABC maintainABC maintain Remove the cause & precipitating factorsRemove the cause & precipitating factors IV fluid dextrose saline & Inj. ThiamineIV fluid dextrose saline & Inj. Thiamine Maintenance of fluid, electrolytes & calorieMaintenance of fluid, electrolytes & calorie Diet – Restriction of protein dietDiet – Restriction of protein diet High glucose dietHigh glucose diet Avoid constipation – Lactulose 15-20ml X 3 times a dayAvoid constipation – Lactulose 15-20ml X 3 times a day Antibiotics : Antibiotics :

NeomycinNeomycin AmpicillinAmpicillin MetronidazoleMetronidazole

Inj. Vitamin KInj. Vitamin K

Mechanism of action of Lactulose:Mechanism of action of Lactulose: Osmotic laxative effect.Osmotic laxative effect. It reduces pIt reduces pHH of colonic content & thereby prevents of colonic content & thereby prevents

absorption of NHabsorption of NH33.. Incorporates nitrogen into bacteria Incorporates nitrogen into bacteria