INTERNAL MEDICINE
duct occlusion, primary or metastatic neoplasia and
microvascular dysplasia. 1 Less common disorders,
which are associated with HE are: cirrhosis ("end
stage" liver), portosystemic vascular anomalies and juvenile fibrosing liver disorders. 1
Common hepatic disorders in cats which are not
associated with HE include: mild hepatic vacuolar
change, hepatic lipidosis syndrome, cholangitis/cholangiohepatitis (associated with pancreatitis and inflammatory bowel disease), major bile duct occlusion,
primary or metastatic neoplasia.1 Much less common
disorders which are associated with HE are biliary cirrhosis and portosystemic vascular anomalies.1
Encephalopathic Toxins:
Although a variety of toxins have been identified in
influencing HE, the most common one is nitrogen,
both dietary and edogenous, which is detoxified in
the urea cycle in the liver.2,4
Ingestion of a meat-based high protein diet, gastrointestinal bleeding (ulcers or verminosis), azotaemia
(increase blood levels of nitrogenous waste products)
and hypokalaemia (increases neurological sensitivity
to ammonia) are the most common event initiators
for HE in animals with severe liver disease with decreased functional parenchyma or with PSVA.4
The liver has a very large reserve functional capacity,
so this only occurs if a large portion is damaged or if
the shunt fraction is significant.
Ammonia that escapes this urea cycle and enters the
systemic circulation can be metabolized to glutamine
by extrahepatic cells such as astrocytes and skeletal
muscle.5 Glutamine is either excreted in urine or metabolized back to ammonia for re-entry into the urea
cycle. In severe liver failure (be it from acute toxic
damage or large portosystemic shunts), the astrocytes
have to take on a larger detoxification role. Astrocytes
contain glutamine synthetase and detoxify ammonia
by converting glutamate to glutamine. 5 Glutamine is
however able to enter the astrocytes’ mitochondria
where it is metabolized back to ammonia, leading to
mitochondrial damage and cell swelling. Astrocyte
swelling is a hallmark histopathologic change observed in acute HE. 5
Ammonia itself is neutrotoxic, and elevations in blood
ammonia cause neurological derangements. Recent
studies have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. 5
Manipulation of nitrogen:
Different proteins have different influences on blood
ammonia and amino acid concentrations. Proteins
containing haeme groups (red meat) are especially
encephalogenic whereas diets containing dairy- and
vegetable-protein are less so. Plant and dairy derived
proteins have been shown to prolong time to development of HE and lessen its effects in dogs.3 Condon
and colleagues investigated the occurrence and severity of neurologic symtoms as well as the survival
time of dogs with experimentally induced portosystemic shunting and HE, when they were fed different
protein sources (eg, meat, fish, and milk).6
Clinical signs occurred more rapidly and were more
severe in dogs fed a meat protein diet when compared to dogs fed a fish diet. The best results were
seen with a diet based on milk protein. The survival
time of dogs fed fish- or milk-derived proteins was almost twice as long as that of dogs fed a meat-based
diet. 6 In patients with HE, non-meat protein sources
such as soy or dairy protein may produce lower blood
ammonia concentrations than meat sources.5
Dietary manipulation of protein is not the only mechanism to manage the build up of ammonia in the blood
stream. Protein tolerance can be increased by using
lactulose, antibiotics and soluble fibre.
Lactulose lowers the gastrointestinal pH trapping the NH3 as Nh4+in the GIT. Lactulose also
changes the intestinal flora from a proteolytic to a
fermentative type and decreases food and faecal
transit time, preventing constipation and allowing
less time for absorption of ammonia.
Antibotics: Urease producing bacteria are also responsible for the production of a lot of ammonia in
the GIT and appropriate antibiotic treatment (metronidazole at 7.5 mg/kg oid / bid rather than the
normal 15mg/kg bid) or neomycin (22mg po bid
will limit the numbers of this bacteria, and thus the
amount of free ammonia available for uptake.
Fibre fermentation increases faecal bulk, increases
the unstirred water layer adjacent to the enterocyte, decreases intestinal transit time, binds enteric
toxins, stimulates enteric IgA production and alters
resident enteric flora all of which are beneficial.
Portosystemic vascular anomalies (PSVA)
The most frequent cause of HE are PSVA, which
have an incidence of between 1 and 5% of the population and are more common in pure bred animals
and certain breeds such as Yorkshire Terriers and Irish
Wolfhounds.5 Furthermore, all chronic liver diseases
associated with formation of fibrosis develop portal
hypertension, which may lead to acquired portosystemic shunting and then may result in HE.5
Most PSVA are diagnosed in young growing dogs and
cats. It is especially important to consider maximising
protein tolerance by using other modalities of managing HE when dealing with immature animals. These
animals still need to grow, so protein restriction to
prevent HE needs to be strictly balanced against the
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