Hepatic encephalopathy is a disease characterized by central nervous system disorder in association with liver failure and portosystemic shunts. This condition is usually caused by a birth defect that leads to blood vessel abnormalities within the liver. In rare cases, it may result from a liver enzyme deficiency. Portoystemic shunts cause absorbed intestinal toxins bypass the liver where they are inactivated. After bypassing the liver, the toxins exert direct or indirect adverse effects on the central nervous system. Substances implicated in the development of hepatic encephalopathy are ammonia, mercaptans, short-chain fatty acids, skatoles, indoles, and aromatic amino acids.1 Astrocytes are particularly vulnerable to the effects of ammonia in the brain. Astrocytes are a type of glial cell found within the central nervous system, which are involved in providing nutrients for neurones. The blood brain barrier remains anatomically intact in this disease. However, studies have demonstrated an increased permeability to ammonia with increasing severity of disease. In acute liver failure, an increased brain ammonia concentration causes astrocyte swelling leading to the development of cytotoxic brain swelling (edema).2
Congenital Portosystemic Shunts
The congenital portosystemic shunt is more commonly seen in purebred than in mix-breed dogs. Most commonly affected breeds include the Miniature Schnauzer, Yorkshire Terrier, Cairn Terrier, Australian Cattle Dog, Old English Sheepdog (Bobtail), and Maltese. Most animals are affected by 2 years of age, often by 6 months of age. Owners' concerns are commonly related to neurological, gastrointestinal, and urinary tract disorders. Furthermore, affected animals may have a history of stunted growth or failure to gain weight compared with unaffected littermates. Nervous system signs are usually evident in puppies before they are 6 months of age and include "staring into space," whining, aggression, and agitation. In advance disease, lethargy and confusion, frequently progressing to coma, abnormal involuntary movements of the extremities, trunk, jaw, or eyes, seizures and muscle spasms can be seen.
The most common laboratory test used to diagnose hepatic encephalopathy is the measurement of arterial blood ammonium. The goal of therapy is to control the disease-causing mechanisms responsible for inducing the encephalopathy, while the liver attempts to regenerate sufficient tissue to maintain life. This is accomplished by reducing the entry, production and absorption of gastrointestinal toxins and by administering systemic drugs to counteract their harmful effects. The mainstays of therapy for encephalopathy involves reduction of protein intake, and suppression or elimination of urease-producing intestinal bacteria. In addition, steps must be taken to recognize and eliminate any factors which may have induced the encephalopathy. For animals with signs of encephalopathy, all oral intake of food should cease until CNS signs abate. This is particularly important for protein. Cessation of food intake eliminates dietary sources of ammonia, toxic amines, aromatic amino acids, and short chain fatty acids which induce encephalopathy. Additional supportive measures may be necessary in the management of animals with this condition. In patients with hepatic failure, parenteral fluid therapy is often required for several days.
Maltese dogs are believed to be predisposed to congenital portosystemic shunts
The current thinking is that although ammonia is the major culprit responsible for the hepatic encephalopathy, the presence of local and systemic inflammation and the release of reactive oxygen species (free radicals) further exacerbate the cerebral effects of ammonia. Anti-inflammatory and anti-oxidative strategies offer real treatment options to patients with this disease in the future.2
- Richard W. Nelson, C. Guillermo Couto. Small Animal Internal Medicine.
- Amit S Seyan, Robin D Hughes, and Debbie L Shawcross. Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress