Portosystemic Shunt

Description

Portosystemic shunts (PSS) are anomalous vascular connections between the portal and systemic venous systems. These vessels shunt blood from the hepatic portal vein (deriving from the stomach, intestines, pancreas and spleen) directly into systemic venous system, bypassing the liver.

Portosystemic shunts may be congenital or acquired in disease the cause portal hypertension. In the developing embryo, the cardinal veins form the systemic abdominal veins (the caudal vena cava, azygos, renal and gonadal veins) whereas the vitelline veins form the hepatic sinusoids, the portal vein and its tributaries, of which the largest are the left gastric, splenic, cranial and caudal mesenteric and gastroduodenal veins. The ductus venosus, a component of the foetal circulation that directs blood directly from the ubilical vein to the vena cava, is also part of the vitelline system. If a functional connection (ductus venosus or otherwise) remains between the vitelline and cardinal systems after birth, a PSS develops. However, in the normal animal, there are numerous non-functional connection between the two systems that may open if the pressure in the portal vein rises, leading to the formation of multiple extrahepatic acquired shunts.

Congenital shunts represent approximately 70% of the total number diagnosed in dogs and constitute the majority of those diagnosed in cats. Congenital shunts usually involve a single (or occasionally double) anomalous vessel which may be located outside of the hepatic parenchyma (extrahepatic) or within it (intrahepatic). Extrahepatic shunts accounts for 63% of single shunts in the dog and they are most commonly found in miniature and toy breeds. Intrahepatic shunts are often located within the left lobes of the liver and occur due to persistence of the foetal ductus venosus. This form of shunt is most common in large breed dogs and patent ductus venosus is an inherited condition in Irish wolfhounds. Intrahepatic shunts running through the central or right liver lobes are recognised and these may have a different embryological origin.

Acquired shunts represent approximately 20% of those diagnosed in dogs and they often consist of multiple small vessels. They arise due to portal hypertension, following an increased resistance to portal blood flow. The increased pressure in the portal vein and its tributaries causes numerous non-functional microvascular communications with the systemic venous system to open. The causes of portal hypertension are numerous and they may be divided into pre-hepatic, hepatic and post-hepatic:

• Pre-hepatic
  • Right-sided congestive heart failure, including cardiac tamponade.
• Hepatic
  • Acute fulminant hepatitis, chronic hepatic failure with fibrosis or neoplasia
• Post-hepatic
  • Thrombosis of the portal vein, hepatic arteriovenous fistulae and congenital hypoplasia of the portal vein.

The pathophysiology of PSS relates to the shunting of portal blood directly from the systemic circulation, resulting in hyperammonaemia and hepatic encepalopathy. Animals with PSS also have reduced function of the hepatic component of the monocyte phagcoyte system (chiefly the Kupffer cells) and they often develop bacteraemia. Gram negative bacteria deriving from the GI tract are involved most commonly.

Signalment

Congenital portosystemic shunts are diagnosed regularly in dogs under one year of age, although they may be ten years old or more at presentation. Extrahepatic shunts occur most commonly in dogs of the small or toy breeds, including Shih tzus, West Higland white terriers, Maltese terriers and Yorkshire terriers. Intrahepatic shunts are much less common and occur in larger breeds such as Irish wolfhounds (in which patent ductus venosus is thought to be inherited), golden retrievers and Australian cattle dogs. The condition occurs occasionally in cats, horses, cows and pigs.

Acquired shunts occur in animals with portal hypertension, of which the most common causes are chronic hepatitis in dogs and cholangitis in cats.

Diagnosis

Clinical Signs

All portosystemic shunts are likely to cause hepatic encephalopathy(HE) and PSS is the major cause of this disease. HE mainly causes waxing and waning neurological signs, including central blindness, seizures, depression and bizarre behaviour. Cats often show hypersalivation/ptyalism.

In additon, animals with congenital PSS may show the following signs:

• Failure to thrive, small body size or weight loss. It may be useful to compare the animal to its littermates to assess whether it is stunted.
• Urinary tract signs, including dysuria, stranguria, haematuria and pollakiuria. These signs occur because an increased blood ammonia concentration decreases the ability of enzymes to convert uric acid to allantoin, resulting in urate urolithiasis and urethral obstruction. Ammonium biurate are the most common uroliths to be formed.
• Polyuria and polydipsia occur for reasons that are not fully understood. Urea synthesis is reduced in animals with PSS (because ammonia is not taken up by the liver in the normal way) and a reduction in the urea concentration of the renal medulla reduces the ability of the kidney to concentrate urine. The hypofunctional liver probably also degrades cortisol at a reduced rate, increasing the circulating concentration of this diuretic hormone.
• Intermittent gastro-intestinal signs such as vomiting and diarrhoea.
• Ascites may occur due to hypoalbuminaemia.
• Bleeding tendencies due to coagulopathy, but this condition is often subclinical.
• Cats may develop copper-coloured irises because they do not produce the normal yellow/green pigments in their livers.
• Animals may have other congenital abnormalities, including hernias and cryptorchidism.

Animals suffering from primary liver disease with acquired PSS may show signs associated with the underlying disease, including icterus, hepatomegaly, pain on abdominal palpation, inappetance and polyuria and polydipsia. Such animals may also show ascites due to portal hypertension and this may be a possible source of confusion as the same sign is seen with congenital PSS.

Laboratory Tests

Haematology

Animals with congenital PSS often have microcytic normochromic red blood cells due to sequestration of iron. Leucocytosis may occur as a response to bacteraemia due to a reduction hepatic phagocytic activity.

Animals with inflammatory liver disease may have leucocytosis of various types and may have acanthocytic red blood cells.

Biochemistry

The following features might be expected on a biochemical profile of an animal with a congenital PSS:

• Decreased serum urea concentration, due to reduced hepatic synthesis
• Hypoalbuminaemia due to reduced synthesis.
• Hypocholesterolaemia due to disruption of the entero-hepatic circulation so that cholesterol must be used constantly to synthesise new bile acids because those returning from the GI tract cannot be extracted by the liver in sufficient quantities.
• Hypoglycaemia, which often occurs with acute HE.

Other Tests

• Increased postprandial ± preprandial bile acid concentrations. Bile acids are normally removed from the portal blood by the liver but, in an animal with PSS, they enter the systemic venous system directly. If the preprandial level is elevated beyond ~100 umol/l, a bile acid stimulation test will not achieve any higher sensitivity for the detection of PSS. A bile acid stimulation test is performed by measuring preprandial bile acids, feeding the animal and measureing post prandial bile acids two hours later. The preprandial sample may occasionally be higher than the postprandial if a gall bladder contraction occurred just before the first sample was taken.
• Increased blood ammonia concentration is diagnostic of PSS for the same reasons as are elevated bile acids. An ammonia tolerance test can be performed by administering ammonium chloride (or a small meal) to a fasted animal and measuring the change in blood ammonia level. Samples must be frozen immediately after collection as continued red blood cell metabolism will artificially raise ammonia levels in stored samples.
• Reduced serum iron concentration due to sequestration.
• Clotting times can be measured in animals where a coagulopathy is suspected.
• Analysis of urine will show that it has a low specific gravity and cytological examination may reveal the presence of urate crystals which resemble 'thorn apples' or 'mites'. If the animal is suffering from cystitis or urethral obstruction due to urolithiasis, haematuria, pyuria or proteinuria may also be detected.

Diagnostic Imaging

Radiography

A definitive diagnosis relies on visualisation of the shunting blood vessel but radiography may reveal changes that are supportive of a diagnosis of PSS:

• Renomegaly is thought to occur as the kidneys attempt to remove and metabolise ammonia
• Microhepatica probably occurs because the liver is deprived of growth factors from the pancreas and other abdominal organs which are usually carried to it in the portal blood, for example the somatomedins (insulin-like growth factors, IGFs).
• Urate uroliths are radiolucent and will not be detected by radiographs.

Ultrasonography

The shunting vessel may be identified by ultrasound scan, especially if a colour flow Doppler facility is available. Congenital shunts are usually thin-walled, tortuous vessels with turbulent flow and it should be noted that they may run between the tributaries of the portal vein and the azygos vein, rather than the portal vein itself. Acquired shunting vessels can often be located around the cranial pole of the left kidney. It may require some skill to find a shunting vessel.

Scans of the urinary bladder and urethra may reveal the presence of urate uroliths and thickening of the bladder wall due to cystitis.

Positive Contrast Portography

The gold standard technique for diagnosis of PSS is mesenteric portovenography, which involves catheterisation of a mesenteric vein and injection of a water soluble iodine-containing contrast medium into the portal circulation. Radiographs are then made to follow the course of the medium through the portal system and liver. The medium can be injected percutaneously into the spleen (under ultrasound guidance) in a less invasive variant of this technique but the spleen may overly the location of the shunt in the subsequent radiographs.

Nuclear Scintigraphy

A further technique available in some veterinary hospitals is nuclear scintigraphy. A radioactive substance (pertechnetate Tc 99m) bound to a marker substance is administered by high colonic infusion and a gamma camera is used to image the liver and heart. In animals with a shunt, the material will reach the heart at a faster rate (within 2 seconds) than in normal animals.

Treatment

In animals with acquired PSS, the underlying cause should be treated and HE should be managed as described here. Acquired shunts should never be ligated as they occur as a compensatory response to portal hypertension and ligation would increase portal pressure.

Animals affected by congenital PSS may be managed either medically or surgically but a recent study has shown that those undergoing surgical ligation of the shunting vessel have a longer median survival time. Medical management is often employed in those animals that show few clinical signs on presentations, are older or which have a shunt that is not amenable to ligation.

Medical Management

A suitable regime would incorporate the following features:

• A diet with protein of high quality and with both soluble and insoluble fibre. Severe protein restriction is only necessary in animals showing signs of HE and it is otherwise detrimental because animals with PSS are often hypoalbuminaemic. A protein of high quality is selected so that excess amino acids are not available to colonic bacteria and suitable sources include cottage cheese in dogs or white fish in cats. Soluble fibre acts in a similar manner to lactulose (below) whereas insoluble fibre decreases intestinal transit time and helps to prevent constipation.
• Lactulose, a synthetic disaccharide that causes acidification of the colonic environment when it is fermented by bacteria. This environment promotes the conversion of ammonia to ammonium and the latter ions are not easily absorbed due to their electrical charge. The trapped ammonia is therefore excreted in faeces. Lactulose is also a cathartic laxative that reduces the amount of time available for colonic bacteria to act on surplus amino acids.
• Administration of oral antibiotics to reduce the numbers of colonic bacteria. Neomycin, ampicillin or metronidazole are commonly used for this purpose.

Surgical Ligation

This is the treatment of choice for congenital PSS but it may cause adverse effects in the post-operative period. Consideration must also be given to the choice of anaesthetic drugs as animals with PSS have a reduced ability to metabolise drugs in the liver and often undergo prolonged recoveries from sedation or anaesthesia. Highly protein bound drugs should also be avoided as their effective concentration will be increased in hypoalbuminaemia.

Anaesthesia

Benzodiazepines should be avoided as they are highly protein-bound and they may also worsen any pre-existing HE. Phenothiazine tranquilisers (acepromazine) and barbiturates should be avoided because they are metabolised in the liver.

During anaesthesia, blood glucose concentration should be measured regularly in animals with congenital PSS as they quickly become hypoglycaemic. Consideration should also be given to warming strategies (such as heat pads, warmed intra-venous fluids and insulation) as they also rapidly become hypothermic.

Surgical Procedure

It is highly advisable to refer animals with PSS to a specialist centre for surgical management and post-operative intensive care. The abdomen should be explored thoroughly in case of multiple shunts and the bladder should also be examined as it may contain urate uroliths that could be removed during the same procedure.

Extrahepatic Shunts

A ventral midline coeliotomy is performed and the shunting vessel is identified. If pre-operative imaging revealed the location of the shunt, it should be found easily but intra-operative mesenteric portovenography can be performed by catheterising a jejunal vein and instilling contrast medium. As a guide, the vena cava accepts blood from the renal veins and the small phrenico-abdominal veins before it reaches the hepatic hilus. Any vessel that joins the vena cava bewteen the phrenico-abdominal and hepatic veins is abnormal.

Direct ligation of the shunt will cause a large rise in portal pressure, reducing the venous drainage of the organs contributing to the portal vein. For this reason, a tributary to the portal vein (such as a jejunal vein) should be catheterised to allow the portal pressure to be measured directly during the procedure. When the shunt is ligated, the portal pressure should not rise by more than 10 cm of water from its baseline value and it should not rise above an absolute value of 20-23 cm of water. If the portal pressure rises above this level, the surgeon is likely to notice that the intestines are blanched (due to reduced perfusion), that the pulses in the mesenteric arteries are hyperkinetic, that the intestines show vigorous contractility and that the pancreas appears oedematous. If any of these signs are observed, the shunt should be attenuated rather than completely ligated.

For complete ligation, silk is often used as a suture material in dogs because its presence promotes a fibrous reactions which reinforces the ligature. Although silk is often categorised as a non-absorbable suture material, its strength is lost after 6 months and it is often fully absorbed after approximately 2 years. Better knot security can be achieved if the silk is wet when the ligatures are tied. Since silk does not stimulate a strong inflammatory response in cats, it is preferable to use the synthetic non-absorbable monofilament polypropylene in this species.

If the shunt cannot be ligated, attenuation may be achieved by three major techniques:

• An ameroid constrictor consists of a ring of stainless steel with an collar of casein. When the ring is applied around a vessel, the casein sheath swells gradually to occlude blood flow and it may also stimulate some fibrosis.
• Cellophane banding involves the application of cellophane around the shunt. This material is sutured in place to stimulate fibrosis around the vessel, resulting in gradual occlusion. This material does not stimulate a strong inflammatory response in cats and should not be used in this species.
• Partial ligation is achieved by applying a loose ligature to the shunt so that some blood flow still occurs. In a proportion of animals, a complete ligation will then have to be performed at a later date.

Intrahepatic Shunts

Intrahepatic shunts are much more difficult to locate and ligate than are extrahepatic shunts and owners should be warned of this fact before a procedure is undertaken. The shunt may be located by palpation of a soft area over a hepatic lobe or, if the vessel runs within a left lobe, it may be located where it joins the hepatic vein. Intra-operative ultrasound can also be employed to find a shunt. Extensive dissection may be required to expose a shunt running through the hepatic parenchyma before it can be ligated and an ultrasonic aspirator can be used for this purpose.

Another option involves temporarily occluding the hepatic blood flow and incising into the caudal vena cava (an intravascular approach). The shunt is identified where it enters the vena cava (cranial to the liver) and pledget-buttressed sutures are used to close the mouth of the vessel.

Post-operative Care

The following syndromes may be encountered after ligation of a shunt:

• Intra-abdominal haemorrhage, which may require a further surgical procedure if severe or may be managed with a belly bandage.
• Portal hypertension, causing ascites, haemorrhagic diarrhoea, septic shock and a painful abdomen. The abdominal girth is often measured regularly after the surgical procedure to assess the degree of abdominal distension. Some ascites is to be expected but severe clinical signs warrant a further surgical procedure to loosen the ligature around the shunt. Ascites should resolve over time but it can be managed with the diuretic spironolactone (because it occurs in part due to inappropriate activation of the renin-angiotensin-aldosterone system).
• Portal vein thrombosis because portal blood flow may be drastically reduced.
• Seizures or status epilepticus, particularly in small breeds of dog. Seizures occur most commonly 1-3 days after ligation and probably result from rebalancing of neurotransmitter levels in the CNS. Long-term anticonvulsant therapy may be required and some animals may acquire permanent defects, such as blindness.

Prognosis

The prognosis for outcome depends on the age of presentation and the urea concentration at presentation, with older dogs with higher levels of urea having better outcomes. Dogs usually respond very well to total surgical ligation if they do not experience severe adverse effects in the week following the procedure but the response in cats is less favourable.

References

• 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.
• Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition) Mosby Elsevier.
• Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier.
• Watson, P. (1997) Decision making in the management of portosystemic shunts In Practice 19;106 - 120 [1]

Also known as:

Portocaval Shunt Patent Ductus Venosus Portosystemic Vascular Anomalies