Hepatic Encephalopathy

Signalment

• Relatively common in dog, especially small breed dogs
• Purebred dogs are more at risk

Description

Hepatic encephalopathy is characterised by a complex of neurological abnormalities that may occur in the presence of advanced liver disease. By far the most common cause in dog and cat is Portosystemic Shunt (PSS), although a marked reduction in functional mass of hepatic tissue can also lead to hepatic encephalopathy. In rare cases, when severe acquired shunt due to hepatobiliary disease and congenital PSS have been ruled out, congenital urea enzyme cycle deficiencies and organic acidaemias, where there is lack of ability to degrade ammonia to urea, can be considered.

This is a reversible abnormality of the cerebral metabolism. Its pathogenesis is not yet fully understood. Increased concentration of ammonia level is the most common cause of this disease manifestation, due to its toxicity effect on brain cells. Due to the lack of urea cycle in the brain, ammonia in cerebrospinal fluid (CSF) is detoxified into glutamine. Level of glutamine can be shown to correlate with clinical signs. Aromatic amino acids, especially tryptophan and its metabolites, share an antiport transporter with ammonia in CSF. Consequently, dogs with congenital PSS are reported to have increased aromatic amino acid concentrations in CSF. Increased ammonia concentrations also have a number of other effects on the central nervous system, including a reduction in serotonin activity, an increased in NMDA (N-methyl-D-aspartic acid) and peripheral-type benzodiazepine receptors.

The sources responsible for an increase in ammonia levels include:

• the bacterial and intestinal breakdown of urea by urease, which then diffuse into the colon from the blood.
• the bacterial breakdown of undigested amino acids in the colon.
• the catabolic metabolism of glutamine as an energy source by small intestinal enterocytes.
• endogenous hepatic protein metabolism by excess dietary protein intake, breakdown of lean body mass and gastrointestinal bleeding.

Diagnosis

Clinical Signs

Dog

Typical signs include:

• anorexia, depression and lethargy
• aimless wandering, head pressing, circling and pacing
• central blindness
• poor growth rate
• gastrointestinal signs such as vomiting
• coma (uncommon)
• seizures (uncommon)

Other signs include:

• temporary resolution of clinical signs with antimicrobial therapy
• prolonged recovery from sedation or anaesthesia
• polyuria and polydipsia in 33% of cases

Cat

Typical signs include:

• well grown and in good body condition which in contrast to dogs
• hypersalivation or ptyalism is the most commonly reported clinical feature, but rarely reported in dogs
• seizures, found in 50% of cases, but uncommon in dogs
• anorexia, vomiting and diarrhoea, polyuria and polydipsia are less common
• compulsive behaviour is less common compared to in dogs

Laboratory Tests

Biochemistry

• Hypoproteinaemia
• Mild to moderate increase in alanine aminotransferase (ALT) and alkaline phosphatase (ALP)
• Decreased blood urea nitrogen (BUN)
• Hypoglycaemia in a small number of dogs

Other Tests

• Fasting hyperammonaemia
• Increased postprandial ± preprandial bile acids

Diagnostic Imaging

Radigraphy

Abdominal radiography shows microhepatica and often renomegaly. Renomegaly may relate to an altered splanchnic blood flow or to an increased metabolic activity of the kidney due to hyperammonaemia. These findings in a young dog are highly suggestive of Portosystemic Shunt.

Confirmation of a Portosystemic Shunt requires visualisation of the shunting blood vessel. This may be done with either ultrasonography or contrast portography or at surgery.

Treatment

Surgical management

• Surgical ligation of shunt is recommended in cases of Portosystemic Shunt.

Medical management

• Enemas to decrease the amount of bacteria in the colon.
• Oral antibiotics such as ampicillin, neomycin or metronidazole can be given initially reduce the amount of bacteria in intestines and hence decrease the production of ammonia.
• Lactulose PO
  • This is a synthetic disaccharide which is metabolised by the acidifying colonic bacteria. Ammonia is converted into ammonium ions, which cannot be absorbed and hence trapped in the colon and excreted in the faeces. Lactulose also acts as an osmotic laxative, allowing more faeces and bacteria to be washed out.
• A high carbohydrate, low protein (2g/kg/day) and low fat diet is recommended.
  • The aim is to provide adequate nutrients and energy to support hepatic tissue repair, reduce the metabolic load on the liver and minimise the development of hepatic encephalopathy

Prognosis

In cases of PSS, the prognosis in dogs for resolution of clinical signs after total surgical ligation is excellent. However, the response of cat to surgical intervention in cats is less promising than in dogs.

References

• Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition) BSAVA
• Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier.
• Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition) W.B. Saunders Company.

From Pathology

Clinical

• non-specific neurological signs (attributed to the retention of ammonia and gamma aminobutyric acid in liver failure and their effects on the brain)
  • dullness
  • apparent unawareness of surroundings
  • pointless or compulsive movements
  • mania
  • generalised convulsions

NB: usually soon followed by death

Microscopically

• lesions in the brain vary in expression
  • most species may show myelin degeneration consisting of vacuoles between the grey and white matter
  • the horse may show very little visible neural changes, perhaps an increase in astrocytes

Causes

Portosystemic Shunting

Chronic liver damage

• due to ingestion of toxic compounds over a long period of time
• E.g. ragwort