The pathophysiology of hepatic encephalopathy (HE) is complex and still poorly understood both in veterinary and human patients but is thought to reflect insufficient hepatic capability to deal with hormones, toxins and other components of metabolism. The pathogenesis is multifactorial, involving increased blood ammonia, other synergistic toxins, alterations in monoamine neurotransmitters, alterations in amino acid neurotransmitters, GABA, glutamate, glutamine and increased cerebral levels of endogenous benzodiazepine-like compounds. Elevated peripheral and central concentrations of manganese have been recently identified in affected animals. It seems that the only consistent finding is that none of these factors will reliably induce HE on their own, underlining that this is not a straightforward problem. It may also be that some dogs with neurological signs and a diagnosis of PSS actually have concurrent central neurological disease. HE can be triggered by many factors including feeding, constipation, gastrointestinal bleeding (effectively a high protein ‘feed’), sedatives, anaesthetics, azotaemia, hypoglycaemia, hypovolaemia and infection.
NB The majority of animals with congenital shunts are identified at less than 1 year of age; however those with moderate, mild or atypical signs may not be diagnosed until middle age. Traditionally, patients above 2 years of age were held to have poorer outcomes however the available clinical evidence does not support this and older animals should not be automatically viewed as non-surgical.
The signalment, clinical signs and history will often be suggestive of a PSS; however there are other conditions which may present in a very similar manner so a full diagnostic work up is essential in every case and assumptions should not lead to shortcuts being taken. This also ensures that secondary complicating factors are not missed, such as clotting abnormalities requiring management prior to surgery.
1) Haematology and biochemistry:
Microcytosis +/- concurrent anaemia is seen in up to 72% of dogs. This anaemia typically resolves following surgical closure of the shunt, and is probably due to altered serum iron concentrations and functional defects in iron transport.
- Leukocytosis is variable, and may be related to inadequate clearance of bacteria and toxins through the portal system.
- Hypoalbuminaemia and decreased total protein.
- Low blood urea nitrogen concentrations
- Low cholesterol and glucose levels
- Elevated liver enzymes
- Increased fasting ammonia levels
2) Urinalysis and bacteriology:
- Low urine specific gravity
- Ammonium biurate crystalluria or urolithiasis
- +/- secondary cystitis
3) Bile acids
Primary bile acids are synthesised in the liver, conjugated with taurine, secreted into the bile canaliculi and stored in the gall bladder. After a meal, the gallbladder contracts releasing bile acids into the intestines, where they enhance fat digestion and absorption. In the distal ileum a bile acid-sodium coupled transporter catches the bile acids and brings them back to the portal circulation. Efficient uptake and resecretion by hepatocytes gives ‘enterohepatic circulation’ of >95% of all bile acids, with the remaining 5% or so being lost in the faeces. Shunting of resorbed bile acids to the systemic circulation means that most animals with PSS will have elevated bile acids, although there are other conditions that may also cause elevation of bile acids. In addition to measuring fasting bile acids, a bile acid stimulation test should be performed, to obtain paired pre- and post prandial samples.
4) Resting serum ammonia levels and ammonia tolerance tests
Reduced ammonia metabolism means that baseline ammonia levels are likely to be increased, although they can be normal in up to 20% of cases if there has been a period of prior medical management or a long period of fasting. Some breeds are known to have higher than normal ammonia levels e.g. IWH. The ammonia tolerance test is quite cumbersome, and carries inherent risks in animals with impaired liver function.
Nuclear scintigraphy is a non-invasive means of evaluating the presence of shunting but its clinical usefulness is limited. In normal animals technetium pertechnetate when infused into the mid-proximal colon will be transported through the portal system to the liver. In animals with a shunt, a greater proportion of the technetium is carried rapidly past the liver and highlights the heart. The shunt fraction compares activity in the liver with activity in the heart on the first passage of the radiopharmaceutical. In a normal dog, the shunt fraction should be < 15%. Animals with congenital shunts should have shunt fractions in excess of 60% but there is a lot of variability. Another issue is that it does not allow imaging of the portal circulation and cannot differentiate reliably between single and multiple shunts, nor intra versus extrahepatic shunts and therefore it is of limited use for pre-surgical planning. Trans-splenic scintigraphy provides superior scans with more reliable information regarding shunt location and number, but it carries a greater risk associated with ultrasound guided injection into the splenic parenchyma in patients prone to clotting abnormalities.
Ultrasonography can identify the presence of shunt vessels, and also allows evaluation of liver size, parenchymal texture and arborisation of blood vessels. In addition, the bladder and kidney can be evaluated for renal architecture, crystalluria and uroliths. Colour flow Doppler, if available, allows identification of turbulence patterns within the vena cava and portal vein typically associated with a shunting vessel(s). Accuracy of ultrasound for identification of PSS varies widely, and it is generally recognised that the diagnostic usefulness of ultrasonography is heavily dependent on the skill and experience of the operator.
This has been historically considered to be the ‘gold standard’ for diagnosis. Operative portography with injection into a mesenteric vein provides excellent imaging of the portal system and vascular anomalies, but does of course require general anaesthesia and a minor surgical procedure. Where advanced imaging is available then either CT or MRI can be used with peripheral contrast injection via an intravenous catheter to obtain excellent images. Depending on the preference of the individual surgeon, the facilities available and the stability of the patient under anaesthesia, it is often possible to follow CT or MRI angiography with definitive surgery. If operative portography is preferred then availability of radiographic facilities in theatre allows both imaging and surgical correction under the same anaesthetic.
PSS: The role of medical management
Where surgery is contra-indicated, for example where there is portal vein atresia, medical management is the only appropriate treatment option. Medical management can improve survival times, but a normal life span is very unlikely and quality of life can be variable. Surgical correction is considered the treatment of choice for patients with PSS.