Genetic Welfare Problems of Companion Animals

Irish Wolfhound

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 dogs 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. Several surveys have suggested that around 3% of Irish wolfhound puppies are affected.

Summary of Information

(for more information click on the links below)

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 dogs 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 dogs develop progressive dementia, stupor, coma and death. Puppies with congenital PSS usually fail to thrive and are smaller than litter mates due to this malfunction of the liver.

2. Intensity of welfare impact   

Signs shown by dogs seen in the early stages of disease include depression, muscle tremors, drooling, pressing of the head against walls and blindness. It seems likely that affected dogs 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.

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.

4. Number of animals affected

Surveys of Irish wolfhound puppies have indicated that around 3% of Irish wolfhounds have portosystemic shunts (Meyer et al 1995, Ubbink et al 1998, Kerr & van Doorn 1999).

5. Diagnosis

The typical signs of hepatic encephalopathy (depression, tremors, head-pressing etc) in a poorly-growing young dog 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 Irish wolfhound 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 puppy 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.

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)) occurs 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.

Figure 1. Schematic diagram displaying a portosystemic shunt. Due to the presence of one or more abnormal connections between the gastrointestinal tract and the heart (in this case via the caudal vena cava), blood can bypass the liver.

(Image property of www.smalldogsrus.com/liver-shunts, to whom we are grateful for permission to reproduce it here).

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 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 dogs have a single PSS. In cases where there are multiple shunts surgical treatment becomes more difficult. Irish wolfhounds typically have a single intra-hepatic shunt (Swalec 1993, Hunt 2004).

The commonest consequences of PSS in dogs are listed below.

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 encephalopthy because it causes 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 and seizures (fits) but eventually most affected dogs 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. Other signs seen in early stages of the disease are muscle tremors, drooling, 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 litter mates.
3. Increased drinking and urinating (polyuria and polydipsia). The reason why these signs 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 cause increased urine production and thus, increased thirst, in compensation (Rothuizen et al 1995).
4. Other, less common, effects. These include vomiting and diarrhoea, the formation of ammonia and uric acids stones in the urinary tract, ascites (fluid build up in the abdomen) and infections in the blood (bacteraemia) that can also focus in the spine (Hall et al 2003). Occasionally, repeated fever (elevated temperature) can be the only sign of a PSS (Wess et al 2003).

In animals in which the abnormal vessels only partially by-pass the liver, signs of HE 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 straightforward as closing off the abnormal vessel, when the normal vessels are not properly formed, can cause severe effects. 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).

Figure 2. Surgery can be carried out whereby ameroid constrictors are placed around the PSS to close the abnormal connection over a period of several weeks.

(Image property of www.vetsurgerycentral.com, to whom we are grateful for permission to reproduce it here).

Return to top

2. Intensity of welfare impact

Signs shown by dogs seen in the early stages of disease include depression, muscle tremors, drooling, pressing of the head against walls and blindness. It seems likely that affected dogs 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, urinary tract stones and infections - 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 some cases, usually in those with mild signs, it may be possible to control the disease with medication and regulation of diet. However, many animals will deteriorate unless they have surgical treatment, although this is not possible in all cases. Dogs with extra-hepatic shunts, single abnormal blood vessels and those that have not yet developed HE, are more likely to respond well to surgery (Winkler et al 2003, Harvey & Erb 1998). Even with a good outcome, dogs do not necessarily become completely normal (Kummeling et al 2004) and bile acid test results do not usually return to normal (Winkler et al 2003).

Return to top

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 is 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 dogs are left with continuing clinical problems (Center 2006).

Return to top

4. Number of animals affected

Irish wolfhounds are known to be predisposed to PSS (Hunt 2004) and have been shown to be around 10 times more likely to have PSS than mixed breed dogs (Tobias and Rohrbach 2003).

Surveys of Irish wolfhound puppies have indicated that around 3% of Irish wolfhounds have portosystemic shunts (Meyer et al 1995, Ubbink et al 1998, Kerr & van Doorn 1999).

Return to top

5. Diagnosis

The typical signs of HE (depression, tremors, head-pressing etc) in a poorly-growing young dog should raise the suspicion of PSS. Routine blood tests may show variable changes in these dogs and, although results may raise suspicion of PSS, they are not conclusive. Other findings seen sometimes in animals with PSS include enlarged kidneys and a heart murmur – these, again, are not conclusive (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, 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 dog 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) but has to be used more carefully in this breed than others as normal Irish wolfhound puppies often have higher levels than other dogs (Meyer et al 1996). 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 dogs 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 (D'Anjou et al 2004, Lamb 1996). 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).

Return to top

6. Genetics

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

Return to top

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 puppy is sold by a breeder. The details of the genetic basis of PSS in Irish wolfhounds are unclear and it is not known if unaffected animals can carry the deleterious gene(s).

There is no way of determining whether an animal is a carrier but von Burgistein (2007) estimated that between 24.8 and 30.1% of Irish wolfhounds are clinically normal carriers of the genes involved with PSS and so might perpetuate the condition.

Return to top

8. Methods and prospects for elimination of the problem

It appears that PPS became much more common in Irish wolfhounds between 1984 and 1992 (Meyer et al 1995) and there is similar evidence of an increase in the prevalence of PSS in other breeds (Tobias and Rohrbach 2003). This may be due to increased awareness and detection or because the genes responsible have become more common in the population.

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. Tobias (2003) found that affected Irish wolfhounds tended to be more inbred than non-affected individuals. 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 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 they are more likely to be carriers than dogs with unaffected relatives (von Burgistein 2007).

Return to top

9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Stephanie Kaufman for assistance in illustrating it.

Return to top

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 22.8.2011

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 22.8.2011

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

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

Hall E, Murphy K and Darke P (2003) Congenital Vascular Anomalies. In: Notes on Canine Internal Medicine 3rd edition. Blackwell Publishing, Oxford. pp 274

Harvey J and Erb HN (1998) Complete Ligation of Extrahepatic Congenital Portosystemic Shunts in Nonencephalopathic Dogs. Veterinary Surgery 27: 413–416

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

Meyer HP, Rothuizen J, Tiemessen I, van denBrom WE and van den Ingh TSGAM (1996) Transient metabolic hyperammonaemia in young Irish wolfhounds. Veterinary Record 138: 105-107

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

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 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

Wess G, Unterer S, Haller M, Hasler A, Reusch C and Glaus T (2003) Recurrent fever as the only or predominant clinical sign in four dogs and one cat with congenital portosystemic vascular anomalies. Schweizer Archiv für Tierheilkunde 145: 363-368

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

© UFAW 2012

Credit for main photo above:

By Tirwhan [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons