Genetic Welfare Problems of Companion Animals

Persian

Portosystemic Shunt

Outline: A portosystemic shunt is an abnormality of the blood circulation in which venous blood from the intestines partially by-passes the liver. Because of this, waste products normally eliminated by the liver, accumulate in the blood and have toxic effects on the brain and other body organs. Affected individuals usually have low growth rates and may show depression, muscle tremors, drooling, and head-pressing against walls (which is thought to be an attempt to relieve headache). It is likely that affected cats feel chronic malaise and pain, which may be severe in some cases. Unless successfully treated (which is difficult and not always possible), there is progressive dementia due to brain damage, leading eventually to coma and death.

Summary of Information

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1. Brief description

A portosystemic shunt (PSS) is an abnormal blood vessel in the abdomen which enables venous blood, that would normally flow from the intestines to the liver, to partially by-pass the liver with the result that the normal functions of the liver are impaired. Congenital PSS, which is present from birth, is known to have a genetic basis.

The most common problem seen in cats with PSS is hepatic encephalopathy (HE). This syndrome can occur whenever the liver is failing in its function to remove toxins from the blood. Instead of being destroyed on their passage through the liver such toxins, arising during digestion and through bacterial fermentation, are carried to the brain and interfere with its functions. Signs are often worse after eating. Affected animals may appear completely normal at other times. Mild signs include depression and seizures (fits) but eventually most affected cats develop progressive dementia, stupor, coma and death. In cats a common sign is excessive drooling. Kittens with congenital PSS usually fail to thrive and are smaller than their littermates due to this malfunction of the liver.

2. Intensity of welfare impact

Signs shown by cats seen in the early stages of this disease include depression, muscle tremors, drooling, pressing of the head against walls and blindness. It seems likely that affected cats feel malaise and discomfort and the head-pressing behaviour may be to try to relieve headache. It is hard to judge the intensity of these welfare effects but it seems reasonable to conclude that they range from mild to severe. Diagnostic investigations and, if attempted, surgical treatment are also likely to have some adverse impact on the welfare of the affected animal and only around half of affected cats do well with combined medical and surgical treatments. The remainder are likely to die, perhaps despite considerable veterinary investigations and treatments.

3. Duration of welfare impact

The malaise and pain caused by hepatic encephalopathy may fluctuate to some extent but is generally likely to affect the animal throughout its lifetime and, unless the condition is successfully treated, will worsen leading eventually to the death of the animal or its euthanasia. Even with successful surgery and ongoing medical treatment continuing adverse welfare impacts from this are common.

4. Number of animals affected

Persians are known to be predisposed to PSS (Tillson & Winkler 2002, Ellison 2004, Hunt 2004). It has been suggested that they are around nine times more likely to be affected than other cats (Ellison 2004), with around 1 in 400 Persians thought to be affected.

5. Diagnosis

The typical signs of hepatic encephalopathy (poor growth rate, depression, drooling, tremors, head-pressing etc) in a young cat should raise the suspicion of PSS. A dynamic bile acid test can be used to diagnose failure of liver function. To confirm the diagnosis, and in every case when a surgical intervention is being considered, a good quality ultrasound examination is required to reveal the presence, and position, of the abnormal blood vessel which causes the disease.

6. Genetics

Various studies have shown that there is a genetic basis to PSS in the Persian but the mode of inheritance has not yet been determined. It is known that it is not sex-linked as both sexes are affected (Meyer et al 1995, Ubbink et al 1998, White et al 1998, Tobias 2003, von Burgistein 2007, van Steenbeek et al 2009).

7. How do you know if an animal is a carrier or likely to become affected?

It is possible to test for PSS using a bile acid stimulation test. This can be done at a young age and before a kitten is sold by a breeder. There is no test to detect animals that may carry the harmful gene(s) without showing signs of the disease themselves.

8. Methods and prospects for elimination of the problem

There are no genetic tests for PSS, however, the bile acid stimulation test (see above) is relatively straightforward and can be routinely performed in young animals before they leave the breeder. It is likely that clinical signs will appear before the normal breeding age and affected animals should not be bred from. Elimination of this disease would require that the only animals used in breeding programmes are those that come from lines with a better than average “breeding value”, ie they have a history of showing a lower incidence of the disease than expected, and ideally those whose ancestry and relatives are free of the disease. Other genetic conditions must also be considered in calculating the breeding value.

For further details about this condition, please click on the following:
(these link to items down this page)

• Clinical and pathological effects
• Intensity of welfare impact
• Duration of welfare impact
• Number of animals affected
• Diagnosis
• Genetics
• How do you know if an animal is a carrier or likely to become affected?
• Methods and prospects for elimination of the problem
• Acknowledgements
• References

1.  Clinical and pathological effects

A shunt is an abnormal connection between blood vessels. In the condition being described here, the abnormal connection (the portosystemic shunt, PSS) is between the blood vessel that normally conveys blood from the intestines to the liver, the hepatic portal vein, and other blood vessels that return blood to the heart. Which particular vein the blood is shunted to may vary, but the result is that the blood partly by-passes the liver.

Like other organs, the liver has an arterial supply of oxygenated blood from the heart, but unlike others, it also has a second blood supply; from the hepatic portal vein. Most veins carry blood back from the body organs towards the heart. Portal veins perform a different function, carrying blood from one organ to another and the hepatic portal vein conveys blood from the stomach and intestines (and related organs), rich in substances absorbed from these, to the liver. These substances include both nutrients and toxins. The liver has multiple functions and among the most important of these are the processing of nutrients and the breakdown, recycling and excreting of waste products.

By interfering with the normal flow of blood to the liver, the portosystemic shunt has the effect of impairing these functions. This has two important effects. The first is that the liver fails to grow because it is starved of nutrients. The second is that toxic substances, eg ammonia absorbed from the intestine, are not dealt with by the liver and so enter general blood circulation causing damage and dysfunction, particularly to the brain.

Although the exact position of the abnormal vessel is of little consequence to the natural disease outcomes, it can make a difference to how easily it can be treated. Extra-hepatic shunts (those outside the liver) may be more easily accessed at surgery than those within it. Many cats have a single PSS. In cases where there are multiple shunts surgical treatment becomes more difficult. Persians typically have a single extra-hepatic shunt (Van Gundy et al 1990, Ellison 2004).

Some consequences of PSS in cats are listed below (Ellison 2004).

1. Hepatic encephalopathy (HE). Encephalopathy means disease of the forebrain and hepatic means related to the liver. This syndrome can occur whenever the liver is failing in its function to remove toxins from the blood. For example it occurs when liver tissue has been lost through long-term liver disease. A PSS leads to hepatic encephalopathy because it allows blood to by-pass the liver. Toxins produced by digestion and by bacteria living in the intestine, which are normally broken down in the liver, are instead carried directly to the brain and interfere with its normal functions. The forebrain - the part of the brain involved with higher cognitive functions - is particularly susceptible to the effects of such toxins. In later stages of the disease, or when toxin levels are caused to rise, other parts of the brain are also affected. Signs are often worse after eating and animals may appear completely normal at other times. Mild signs include depression, blank staring, circling, manic movements and seizures (fits) but eventually most affected cats will show progressive dementia, stupor, coma and death. Dementia is a serious loss of mental ability, stupor is a dazed state that verges towards unconsciousness and coma is a pathological state of deep unconsciousness. Seizures are seen in around 1/3 of affected cats (Ellison 2004). Drooling (ptyalism) with frequent licking of the lips and nose is particularly common in affected cats. Other signs seen in early stages of the disease are muscle tremors, pressing of the head against walls (to alleviate pain), and blindness (the latter may be brief and temporary whilst a toxic episode lasts).
2. Failure to grow. Because of the liver malfunction, affected puppies usually fail to thrive and are smaller than littermates.
3. Increased drinking and urinating (polyuria and polydipsia). The reason why these sometimes occur is unclear but it may be that metabolic disturbances caused by the PSS result in higher concentrations of the hormone cortisol which can result in increased urine production and thus, increased thirst, in compensation (Rothuizen et al 1995).
4. Other, less common, effects include vomiting and diarrhoea, the formation of ammonia and uric acids stones in the urinary tract which happens in about 10% of affected cats (Ellison 2004).

In animals in which the abnormal vessels only partially by-pass the liver, the signs of disease are generally milder and intermittent (e.g. they may be apparent only after a high protein meal).

Even when the shunt is accessible to surgery, treatment may not be straight forward. Closing off the abnormal vessel, when the normal blood vessels are not properly formed, can cause severe effects (Van Gundy et al 1990, White et al 1996). For this reason, slow closure of the PSS has been recommended (Hunt 2004, Kummeling et al 2004), often using a device that is intended to close the vessel over 4-5 weeks (Vogt et al 1996, Mehl et al 2005).

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2. Intensity of welfare impact

Signs shown by cats seen in the early stages of the disease include depression, muscle tremors, drooling, pressing of the head against walls and blindness. It seems likely that affected cats feel malaise and discomfort and the head-pressing behaviour may be to try to relieve headache caused by the build up of waste products and toxins in the blood. It is hard to judge the intensity of these welfare effects but it seems reasonable to conclude that these range from mild to severe. The disease can also cause confusion and inability to perform normal behaviours and activities such as walking. 

The less common effects of PSS - vomiting, diarrhoea and urinary tract stones - can also cause pain, distress and malaise.  

Diagnostic investigations and surgical interventions to treat PSS may, themselves, have adverse welfare impacts (through stress caused by repeated visits to vets, administration of anaesthetics, and the pain and distress of surgery). In occasional cases, usually in those with mild signs, it may be possible to control the disease with medication and regulation of diet. However, most animals will deteriorate unless they have surgical treatment.

Around 10% of cats cannot be treated surgically because the nature of their shunts make them impossible to close. These individuals are likely to die. Another 10% of cats operated on do not survive the procedure. Many cats require a second surgery to get a good clinical response. Cats with extra-hepatic shunts, single abnormal blood vessels and those that have not yet developed hepatic encephalopathy, are more likely to respond well to surgery. In all, around half of affected cats do well (Van Gundy et al 1990, White et al 1996, Ellison 2004). Even with a good outcome, cats do not necessarily become completely normal and may require ongoing medical treatments (Ellison 2004, Kummeling et al 2004). Bile acid test results, which reflect liver function, do not usually return to normal (Winkler et al 2003).

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3. Duration of welfare impact

The malaise and pain caused by hepatic encephalopathy may fluctuate to some extent but is generally likely to affect the animal throughout its life. The disease and these welfare consequences of it are likely to progressively worsen, leading eventually to the death of the animal or its euthanasia, unless the condition is successfully treated. The duration of the welfare problems therefore can be long (months or years). Many factors affect the success of surgical treatment (Lawrence et al 1992, Hunt 2004, Kummeling et al 2004, Lee et al 2006) and treatment may not alleviate all the adverse welfare effects as around half of surgically treated cats are left with continuing clinical problems that are controlled partially by continuous medical treatments (Ellison 2004, Center 2006).

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4. Number of animals affected

Persians are known to be predisposed to PSS (Tillson & Winkler 2002, Ellison 2004, Hunt 2004). It has been suggested that they are around nine times more likely to be affected than other cats (Ellison 2004) and it has been estimated that around 1 in 400 Persians are affected.

It has been suggested that Persians with yellow eyes are more likely to have a PSS than cats with eye of another colour (Ellison 2004).

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5. Diagnosis

The typical signs of HE (poor growth rate, depression, tremors, head-pressing etc) in a young cat should raise the suspicion of PSS. The results of routine blood tests may show variable changes in these cats and, although results may raise suspicion of PSS, they are not conclusive. Other findings seen sometimes in animals with PSS are vague and more commonly associated with other diseases (Swalec 1993).

A dynamic bile acid test is the usual means of diagnosing liver function failure as the cause of the clinical signs (Kerr & van Doorn 1999, Ellison 2004, Center 2006). This is not specific for PSS as liver function may fail for a variety of reasons. However, in a young animal, a congenital PSS is the most likely explanation. The dynamic bile acid test involves measuring the bile acids in samples of blood taken after withholding food from the cat for 12 hours and again two hours after a meal. Measurement of blood ammonia level may also be informative (Winkler et al 2003, Gerritzen-Bruning et al 2006). The bile acid stimulation test can give false negative results so a normal result does not totally exclude the possibility that an individual has a PSS (Center 1990). How often a false negative result occurs depends on the type of cases being tested, more severely affected cats are less likely to have false negative results than mildly affected ones.

To confirm the diagnosis, and in every case when a surgical intervention is being considered, a good quality ultrasound examination is required to reveal the presence and position of the abnormal vessel. As well as confirming the diagnosis this will inform what surgical options there are for treatment (Lamb 1996, D'Anjou et al 2004, Ellison 2004). There are also other diagnostic techniques that can be used to image the blood supply to and around the liver and to guide the surgical treatment or other management of these cases (Tobias 2002, Center 2006, Lee et al 2006).

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6. Genetics

The predisposition of Persian cats to the disease is evidence that it has a a genetic basis but the mode of inheritance has not yet been determined.

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7. How do you know if an animal is a carrier or likely to become affected?

There is no genetic test for PSS in any breed. It is possible to test animals for PSS using the bile acid stimulation test. This can be done at a young age and before a kitten is sold by a breeder. The details of the genetic basis of PSS in Persians are unclear and it is not known if unaffected animals can carry the deleterious gene(s).

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8. Methods and prospects for elimination of the problem

Whilst there are no genetic tests for PSS, the bile acid stimulation test (see above) is relatively straightforward and can be routinely used to test for the condition in young animals before they leave the breeder. If the test result is normal then the animal is unlikely to have PSS but the test is not 100% reliable (Center 1990, Tobias and Rohrbach 2003, Ruland et al 2010).

In most cases clinical signs appear before breeding age is reached. Affected animals should not be used for breeding.. It has been suggested that diseases with an unknown mode of inheritance should be controlled using the same approaches as for polygenic disorders and this seems relevant here (Bell 2010). Animals that come from lines with a better than average “breeding value”, ie. they have a history of showing a lower incidence of PSS (and other significant conditions with a genetic influence) than expected for the breed, and ideally those whose ancestry and relatives are free of the disease, should be used in breeding programmes (Bell 2007). It has also been recommended that siblings and parents of affected animals should not be breed as, assuming an analogy with other species; they are probably more likely to be carriers than cats with unaffected relatives (von Burgistein 2007).

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Bell JS (2007) Exploring the Mysteries of Liver Shunts. Tufts’ Canine and Feline Breeding and Genetics Conference September 13-14th Strubridge, Massachusetts http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=tuftsbg2007&PID=pr18811&O=VIN accessed 2.11.2011

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. 35th World Small Animal Veterinary Association World Congress Proceedings. 2-5th June 2010, Geneva, Switzerland. http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2010&PID=pr56159&O=VIN accessed 22.8.2011

von Burgistein SRU (2007) Lifespan and Causes of Death in the Irish Wolfhound: Medical, Genetical and Ethical Aspects  Inaugural-Dissertation Zur Erlangung der Doktorwürde der Vetsuisse-Fakultät der Universität Bern http://www.ths.vetsuisse.unibe.ch/unibe/vetmed/housing/content/e8908/e8968/e9097/files9273/Diss_Urfer_2007_ger.pdf accessed 2.11.2011

Center SA (1990) Liver function tests in the diagnosis of portosystemic vascular anomalies. Seminars in Veterinary Medicine and Surgery 5: 94-99

Center SA (2006) Hepatic Vascular Disorders in Small Breed Dogs World Small Animal Veterinary Association World Congress Proceedings http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2006&PID=pr15824&O=VIN accessed 22.8.2011

D'Anjou M-A, Penninck, Cornejo L and Pibarot P (2004) Ultrasonographic diagnosis of portosystemic shunting in dogs and cats. Veterinary Radiology and Ultrasound 45: 424–437

Ellison GW 2004 Portosystemic shunts in cats. In: Proceeding of the Western Veterinary Conference 2004 http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wvc2004&PID=pr05513&O=VIN accessed 19.10.2011

Gerritzen-Bruning M, van den Ingh T and Rothuizen J (2006) Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs. Journal of Veterinary Internal Medicine 20: 13-19

Hunt TG (2004) Effect of breed on anatomy of portosystemic shunts resulting from congenital diseases in dogs and cats: a review of 242 cases. Australian Veterinary Journal 82: 746–749

Kerr MG and van Doorn T (1999) Mass screening of Irish wolfhound puppies for portosystemic shunts by the dynamic bile acid test. Veterinary Record 144: 693-696

Kummeling A, Van Sluijs FJ and Rothuizen J (2004) Prognostic Implications of the Degree of Shunt Narrowing and of the Portal Vein Diameter in Dogs with Congenital Portosystemic Shunts. Veterinary Surgery 33: 17–24

Lamb CR (1996) Ultrasonographic diagnosis of congenital portosystemic shunts in dogs: results of a prospective study. Veterinary Radiology and Ultrasound 37: 281–288

Lawrence D, Bellah JR and Diaz R (1992) Results of surgical management of portosystemic shunts in dogs: 20 cases (1985-1990). Journal of the American Veterinary Medical Association 201: 1750-3

Lee KCL, Lipscomb VJ, Lamb CR, Gregory SP, Guitian J and Brockman DJ (2006) Association of portovenographic findings with outcome in dogs receiving surgical treatment for single congenital portosystemic shunts: 45 cases (2000–2004). Journal of the American Veterinary Medical Association 229: 1122-1129

Mehl ML, Kyles AE, Hardie EM, Kass PH, Adin CA, Flynn A, De Cock H and Gregory CR (2005) Evaluation of ameroid ring constrictors for treatment for single extrahepatic portosystemic shunts in dogs: 168 cases (1995-2001). Journal of the American Veterinary Medical Association 226: 2020-2030

Meyer HP, Rothuizen J, Ubbink GJ and van den Ingh TS (1995) Increasing incidence of hereditary intrahepatic portosystemic shunts in Irish wolfhounds in The Netherlands (1984 to 1992). Veterinary Record 136: 13-6

Rothuizen J, Biewenga WJ and Mol JA (1995) Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release in dogs with hepatic encephalopathy. Domestic Animal Endocrinology 12: 13-14

Ruland K, Fischer A and Hartmann K (2010) Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats. Veterinary Clinical Pathology 39: 57-64

Swalec KM (1993) Portosystemic shunts. In: Disease Mechanisms in Small Animal Surgery 2nd edition. Edited by MJ Bojrab. Lea and Febiger, Philadelphia pp 298

Tillson DM and Winkler JT 2002 Diagnosis and treatment of portosystemic shunts in the cat. Veterinary Clinics of North America. Small Animal Practice 32: 881-99

Tobias KM (2002) Portosystemic Shunts: Diagnosis and Medical Management. Western Veterinary Conference http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2005&PID=pr09545&O=VIN accessed 22.8.2011

Tobias KM (2003) Determination of inheritance of single congenital portosystemic shunts in Yorkshire terriers. Journal of the American Animal Hospital Association 39: 385-389

Tobias KM and Rohrbach BW (2003) Association of breed with the diagnosis of congenital portosystemic shunts in dogs: 2,400 cases (1980-2002). Journal of the American Animal Hospital Association 223: 1636-1639

Ubbink GJ, van de Broek J, Meyer HP and Rothuizen J (1998) Prediction of inherited portosystemic shunts in Irish Wolfhounds on the basis of pedigree analysis. American Journal of Veterinary Research 59: 1553-6

Van Gundy TE, Boothe HW and Wolf A 1990 Results of surgical management of feline portosystemic shunts. Journal of the American Animal Hospital Association 26:55-62

Van Steenbeek F, Leegwater P, Van Sluijs F, Heuven H and Rothuizen J (2009) Evidence of Inheritance of Intrahepatic Portosystemic Shunts in Irish Wolfhounds. Journal of Veterinary Internal Medicine 23: 950–952

Vogt JC, Krahwinkel DJ Jr, Bright RM, Daniel GB, Toal RL and Rohrbach B (1996) Gradual occlusion of extrahepatic portosystemic shunts in dogs and cats using the ameroid constrictor. Veterinary Surgery 25: 495-502

White RN, Forster-van Hijfte MA, Petrie G, Lamb CR and Hammond RA 1996 Surgical treatment of intrahepatic portosystemic shunts in six cats. Veterinary Record 139:314-317

White RN, Burton CA and McEvoy FJ (1998) Surgical treatment of intrahepatic portosystemic shunts in 45 dogs. Veterinary Record 142: 358-365

Winkler JT, Bohling MW, Tillson M, Wright JC and Ballagas AJ (2003) Portosystemic Shunts: Diagnosis, Prognosis, and Treatment of 64 Cases (1993–2001). Journal of the American Animal Hospital Association 39: 169-185

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