Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Cavalier King Charles Spaniel

Cavalier King Charles Spaniel (CKCS)

Pancreatitis

Related terms: Chronic pancreatitis, auto-immune pancreatitis

VeNom term: Pancreatitis (VeNom code: 1592)

Related conditions: Diabetes mellitus, exocrine pancreatic insufficiency

OutlineChronic pancreatitis is a persistent inflammatory disease of the pancreas that causes irreversible changes to the pancreatic tissues resulting in permanent and progressive loss of function. Chronic pancreatitis can be caused by various factors and the aetiology in Cavalier King Charles spaniels is not known. The clinical signs of chronic pancreatitis are often non-specific and many dogs will not show outward signs of malaise until they are in the severe end/terminal stages of the disease. The most common clinical signs of pancreatitis are a reduction or lack of appetite, vomiting, and diarrhoea, abdominal pain and lethargy. The condition affects middle aged to older dogs, of both sexes, and the Cavalier King Charles breed appears to be more at risk of developing the condition than other breeds


Summary of Information

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1. Brief description

The pancreas is situated in the abdomen, close to the small intestine and stomach. It has two distinct functions. The first is an endocrine (hormonal) function: the regulation of the blood glucose level by secretion of the hormones insulin and glucagon. The second, its exocrine function, is the secretion of digestive enzymes (chemicals vital for the digestion of food) into the intestines. Various mechanisms exist to prevent these potentially corrosive chemicals and enzymes in the digestive juice from damaging the pancreas and the surrounding body tissues but when the pancreas is damaged, these chemicals and enzymes can become active inside the organ and cause significant damage.

Pancreatitis is inflammation of the pancreas. It exists in two forms – acute (where the inflammation is sudden, painful and severe) and, the more common, chronic. Chronic pancreatitis is a persistent long-term inflammatory disease of the pancreas that causes irreversible morphological changes to the pancreas, such as with scarring, gradual loss of pancreatic tissue, and a mononuclear inflammatory cell infiltrate (lymphocytic or lymphoplasmacytic). This results in progressive and permanent loss of function, which may progress to exocrine pancreatic insufficiency (EPI), when the damage has been of such severity that not enough pancreatic juice is produced for digestion, and/or diabetes mellitus. An animal that has suffered from acute pancreatitis may go on to experience chronic pancreatitis.

The clinical signs of chronic pancreatitis are often low grade and non-specific and many dogs will not show outward signs of malaise until they are in the severe end/terminal stage of the disease, when nearly all functioning pancreatic tissue has been lost. The most common clinical signs of pancreatitis are abdominal pain, a reduction or lack of appetite, vomiting, lethargy and diarrhoea. Ongoing chronic pancreatitis is often clinically silent, that is, symptom-less until complications arise secondary to the loss of pancreatic function such as diabetes mellitus (which causes increased thirst and urine production) or exocrine pancreatic insufficiency (EPI; signs of which are intractable diarrhoea and weight loss despite a normal or excessive appetite). Other signs include: weakness, depression, fever, haemorrhagic (bloody) diarrhoea and in some cases sudden death.

2. Intensity of welfare impact   

Chronic pancreatitis is the most common form of the disease, but acute episodes are the most frequent cause of welfare problems. Bouts of acute pancreatitis cause suffering from: pain, nausea, chronic vomiting and diarrhoea, lethargy, depression and collapse. Death from shock and multiple organ failure can occur.

Despite the few obvious signs associated with the disease, dogs with chronic pancreatitis may experience recurrent episodes of self-resolving abdominal pain without owners noticing. There may also be significant welfare impacts from the complications associated with chronic pancreatitis. For example, diabetes mellitus may cause severe illness with vomiting, anorexia and collapse.  Treatment of diabetes mellitus is often successful but may have adverse welfare effects through the frequent veterinary visits, injections, forced changes to lifestyle through controlled feeding and exercise, and from possible side effects of treatment. Dogs affected with exocrine pancreatic insufficiency experience chronic hunger and unpleasant diarrhoea.

3. Duration of welfare impact

Dogs with chronic pancreatitis are likely to be middle-aged or old at diagnosis of the disease. The outcomes from chronic pancreatitis in dogs have not been studied but it is assumed that most affected dogs will continue to have at least low-level disease and to be at risk of bouts of acute pancreatitis, the development of diabetes mellitus or the persistence of exocrine pancreatic insufficiency throughout their life.

4. Number of animals affected

Cavaliers appear to be more at risk of developing chronic pancreatitis than other breeds, although the exact prevalence of the disease is not known.

5. Diagnosis

Diagnosis of chronic pancreatitis is not straightforward and may depend on repeated diagnostic tests in order to detect bouts of mild acute pancreatitis which are indicative of ongoing chronic pancreatitis. Histological examinations of the pancreas are usually required for a definitive diagnosis (of pancreatic damage) but these may be made post-mortem. Imaging of the cranial abdomen, especially using ultrasound or CT scans may be helpful in diagnosis of both acute and chronic conditions.

6. Genetics

Cavalier King Charles spaniels are predisposed to chronic pancreatitis but the genetic mechanisms and pattern of inheritance have not yet been fully investigated.

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

There is no known test for identifying individuals who are likely to become affected by chronic pancreatitis. Not all dogs with chronic pancreatitis show outward signs of ill-health and the degree to which affected dogs show outward signs varies. We do know that Cavalier King Charles spaniels are more commonly affected by chronic pancreatitis than other breeds.

8. Methods and prospects for elimination of the problem

Further work is required to determine the genetic nature of chronic pancreatitis in Cavalier King Charles spaniels, and how this condition is inherited, but it may be advisable to avoid breeding between dogs with severely affected relatives, including grandparents, siblings, previous offspring and siblings of parents.


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1. Clinical and pathological effects

The pancreas is situated in the abdomen, close to the small intestine and liver. It has two distinct functions. The first is an endocrine (hormonal) function: the regulation of the blood glucose level by secretion of the hormones insulin and glucagon. The second, its exocrine function, is the secretion of digestive enzymes (chemicals vital for the digestion of food) into the intestines. Only around 2% of pancreatic cells (the islets of Langerhans) are involved in the endocrine function. Most cells are involved in the exocrine, with the production of enzymes, chemicals and fluids that flow, via the main pancreatic ducts, into the small intestine as “pancreatic juice”. The main chemical in this juice is bicarbonate which acts to neutralise the acid produced in the stomach. Enzymes are proteins that act as catalysts in the chemical reactions that break down foodstuffs into molecules small enough to pass through the intestinal wall. These enzymes include: proteases that break down protein into amino acids; pancreatic lipase and phospholipase that break down fats; nucleases that breakdown nucleic acids (DNA and RNA) and pancreatic amylase that breaks down starch and glycogen. Some of the enzymes are secreted as inactive forms that only become active and able to contribute to digestion once activated in the small intestine.

Various mechanisms exist to prevent these potentially corrosive chemicals and enzymes from damaging the pancreas and the surrounding body tissues. The particularly dangerous enzymes, such as trypsin which breaks down proteins, are stored in the pancreas as inert proenzymes eg trypsinogen. These become activated by substances produced in the duodenum (the first part of the small intestine). Other enzymes, in turn, are only activated once exposed to trypsin itself. A second protective mechanism is the presence of enzyme inhibitory substances within the pancreas, which are produced both by the organ and are found in the circulating blood (Kalli et al 2009). When the pancreas is damaged, these chemicals and enzymes often become active inside the organ and cause significant damage. This can occur as a sudden-onset, severe disease (acute pancreatitis) causing destruction of the pancreas with significant effects throughout the body or as a lower-grade process with local inflammation and scarring (chronic pancreatitis).

Pancreatitis is inflammation of the pancreas. It exists in two forms – acute (where the inflammation is sudden, painful and severe) and, the more common, chronic form. Chronic pancreatitis is a persistent long-term inflammatory disease of the pancreas that causes irreversible morphological changes resulting in pain and/or permanent loss of function.  Chronic pancreatitis is associated with scarring, gradual loss of pancreatic tissue, and a mononuclear inflammatory cell infiltrate (lymphocytic or lymphoplasmacytic), in which white blood cells collect at areas of tissue damage and cause inflammation. It has been suggested that Cavalier King Charles spaniels have a propensity to produce scar tissue through the regeneration, thickening and scarring (fibrosis) of the connective tissues and that this may be related to the release of serotonin derived from abnormally large platelets (blood clotting cells) that are typically found in the breed (Cowan et al 2004). As yet, there is little direct evidence to support this theory but research is ongoing, led by Dr Penny Watson at Cambridge Veterinary School (http://www.vet.cam.ac.uk/directory/pjw36@cam.ac.uk).

Chronic pancreatitis differs from acute pancreatitis because the changes to the pancreas in acute pancreatitis are reversible (Watson 2012). Dogs can recover from acute pancreatitis but some may develop an abscess in the pancreas that causes more chronic (longer-term) illness (Kalli et al 2009). An animal that has suffered from acute pancreatitis may go on to experience chronic pancreatitis, and dogs with chronic pancreatitis are probably also more likely to have recurrent bouts of acute pancreatitis.

Pancreatitis can be caused by a variety of factors and the cause in any particular individual is often not known. A high fat diet, being overweight, exposure to certain drugs, trauma and concurrent endocrine disease (diabetes mellitus, hyperadrenocorticism and hypothyroidism), may all contribute to the development of acute pancreatitis (Hess et al 1999). One recent study suggested that the death rate is around 40% (Papa et al 2011). Risk factors for chronic pancreatitis have not been studied to date.

Damage to the pancreas leads to local inflammation and swelling. Disruption to its blood supply can lead to the death of parts, or the entire, pancreas. The damaged tissue is also susceptible to infection by bacteria moving up the pancreatic duct from the intestine. Inflammatory products and toxins from the diseased pancreas enter the general circulation and cause effects elsewhere in the body (Kalli et al 2009). In dogs with chronic pancreatitis, there is progressive loss of function of the pancreas, and this may progress (at the end stage) to exocrine pancreatic insufficiency (EPI), when the damage has been of such severity that not enough pancreatic juice is produced for digestion, and/or diabetes mellitus (Watson 2012).

The clinical signs of chronic pancreatitis are often low grade and non-specific and the pancreas has the capacity to function even if up to 80 or 90 per cent of the pancreas is damaged. Therefore many dogs will not show outward signs of malaise until the severe end/terminal stage of the disease when nearly all functioning pancreatic tissue has been lost (Xenoulis et al 2008). The most common clinical signs of pancreatitis are inappetance (anorexia), vomiting, and diarrhoea. There can be many other signs including abdominal pain, weakness, depression, fever, haemorrhagic (bloody) diarrhoea or sudden death (Bostrom et al 2013). Ongoing chronic pancreatitis is often clinically silent, that is, symptom-less until complications arise secondary to the loss of pancreatic function: diabetes mellitus, in which the control of blood glucose levels  is compromised, and which occurred in 36% of dogs with severe acute pancreatitis in one study (Papa et al 2011), causes affected dogs to exhibit increased thirst and urine production). Dogs with exocrine pancreatic insufficiency (EPI) show intractable diarrhoea and weight loss despite a normal or excessive appetite.

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2. Intensity of welfare impact

Bouts of acute pancreatitis cause suffering from pain, nausea, chronic vomiting and diarrhoea, lethargy, depression and collapse (Kalli et al 2009). In attempting to alleviate pain, some dogs will adopt a “praying” body position - with their head lowered, the fore-legs stretched out in front and the rear end raised (Kalli et al 2009). Death from shock and multiple organ failure is frequent.

Despite the few obvious signs associated with the disease, dogs with chronic pancreatitis may experience recurrent episodes of self-resolving abdominal pain without owners noticing, since the clinical signs are difficult to attribute to an underlying disease.  

In the later stages of chronic pancreatitis, exocrine pancreatic insufficiency may cause chronic hunger and diarrhoea. Veterinary treatment is often aimed to alleviate or reduce the symptoms of chronic pancreatitis, and this may be life-long and sometimes is difficult and have unpleasant side-effects (Hall et al 2003).

Dogs with chronic pancreatitis are also likely to have concurrent endocrine diseases, including diabetes mellitus, hypothyroidism, hyeradrenocorticism and hypoadrenocorticism, all of which may adversely impact on welfare. Cavalier King Charles spaniels are also predisposed to syringomyelia, mitral valve disease and gastrointestinal or renal disease, all of which may adversely impact on welfare Kent et al 2016).

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3. Duration of welfare impact

Chronic pancreatitis in Cavalier King Charles spaniels is likely to be seen in middle-aged or older dogs (Watson et al 2010). Exocrine pancreatic insufficiency, secondary to chronic pancreatitis, was diagnosed in Cavalier King Charles spaniels at an average (median) age of 6 years (range 2-13 years; Batchelor et al 2007).

The outcomes from chronic pancreatitis in dogs have not been studied but it is assumed that most affected dogs will continue to have at least low-level disease and to be at risk of recurrent bouts of acute pancreatitis, the development of diabetes mellitus or the persistence of exocrine pancreatic insufficiency (Xenoulis et al 2008) throughout their life. In a study of 54 Cavaliers, 52% had signs of chronic pancreatitis post-mortem, and 5 of these dogs had severe or end-stage disease but it was the cause of death or euthanasia for only 2 dogs (Kent et al 2016). In a study of 14 dogs with chronic pancreatitis, only one dog died as a direct result of pancreatic disease; 4 dogs died because of hepatic disease or neoplasia (Watson et al 2010).

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4. Number of animals affected

Cavalier King Charles spaniels appear to be more at risk of developing chronic pancreatitis than other breeds, although the exact prevalence of the disease within the breed is not known. Current studies are limited by small or biased populations, and the difficulties in making a formal diagnosis ante-mortem means that data on the incidence or prevalence of the disease are limited.    

In one study, out of 200 unselected dogs that were submitted for post mortem examination in the UK, 51 dogs (25.5%) had signs of chronic pancreatitis, and 6 of these were Cavalier King Charles spaniels (Watson et al 2007). The relative risk of chronic pancreatitis in Cavalier King Charles spaniels was significantly high at 3.2 (95% confidence interval: 2.5-4.1; Watson et al 2007). In a study of 54 Cavalier King Charles spaniels submitted by owners and breeders for post-mortem analysis, histopathological evidence of chronic pancreatitis was observed in 52% of cases (28 of 54 dogs), of which only 13 (46.4%) had shown clinical signs and only 7 (25%) had an ante-mortem diagnosis (Kent et al 2016).  However, in a report of case series report of 61 cases of chronic pancreatitis in Texas, USA, Cavalier King Charles spaniels were not represented among the cases, which might suggest geographic differences in breed-related predispositions to the condition as related to the availability of different breeding lines (Bostrom et al 2013).

In a retrospective UK study of laboratory samples for canine trypsin-like immunoreactivity (cTLI) assays over 12 years (1990 to 2002), the prevalence of exocrine pancreatic insufficiency, likely secondary to chronic pancreatitis, in Cavalier King Charles spaniels was 26.3% (64 dogs of 243; Batchelor et al 2007).

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5. Diagnosis

The diagnosis of chronic pancreatitis is not straightforward since it has similar clinical signs to diseases of other abdominal organs (Hall et al 2003, Kalli et al 2009). Diagnosis of repeated bouts of mild acute pancreatitis are indicative of ongoing chronic pancreatitis (Xenoulis et al 2008). Blood tests can be helpful in making the diagnosis of acute pancreatitis, especially the test for canine pancreatic lipase immunoreactivity (cPLI) or canine specific pancreatic lipase (Spec cPL). Imaging of the cranial abdomen, especially using ultrasound or CT scans may be helpful in diagnosis of both acute and chronic conditions (Kalli et al 2009, Xenoulis et al 2008). Histological examinations are usually required for a definitive diagnosis (of pancreatic damage) but these may be made post-mortem (Watson 2004). Newman and others (2006) have suggested a grading scheme for pancreatic inflammation, including parameters of neutrophilic inflammation, lymphocytic inflammation, pancreatic necrosis, pancreatic fat necrosis, edema, fibrosis, atrophy, and hyperplastic nodules.

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6. Genetics

To our knowledge, the inheritance pattern of chronic pancreatitis has not yet been investigated in Cavalier King Charles spaniels, although we do know that the breed is predisposed to the disease in mid- to late- life.

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

There is no known test for identifying individuals who are likely to become affected by chronic pancreatitis. Not all dogs with chronic pancreatitis will show outward signs of ill-health and the degree to which affected dogs show outward signs varies. We do know that Cavalier King Charles spaniels are more commonly affected by chronic pancreatitis than other breeds.

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8. Methods and prospects for elimination of the problem

Chronic pancreatitis is a complex and multifactorial condition and is often difficult to diagnosis, making it a difficult subject for further in-depth study. In order to explain the high prevalence of the disease in this breed, research is required to determine the genetic nature of chronic pancreatitis in Cavalier King Charles spaniels, and how it is inherited. In the meantime, it may be advisable to avoid breeding between dogs with severely affected relatives, including grandparents, siblings, previous offspring and siblings of parents (Farrell et al 2015.

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9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS), Rosie Godfrey (BVetMed MRCVS) and David Godfrey (BVetMed FRCVS) for their work in compiling this section.

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10. References

 

Batchelor DJ, Noble P-JM, Cripps PJ, Taylor RH, McLean L, Leibl MA and German AJ (2007) Breed Associations for Canine Exocrine Pancreatic Insufficiency. Journal of Veterinary Internal Medicine 21: 207–214. doi:10.1111/j.1939-1676.2007.tb02950.x

Bostrom BM, Xenoulis PG, Newman SJ, Pool RR, Fosgate GT and Steiner JM (2013) Chronic pancreatitis in dogs: a retrospective study of clinical, clinicopathological, and histopathological findings in 61 cases. Veterinary Journal 195: 73–9.

Cowan SM, Bartges JW, Gompf RE, Hayes JR, Moyers TD, Snider CC, Gerard DA, Craft RM, Muenchen, RA and Carroll RC (2004) Giant platelet disorder in the Cavalier King Charles Spaniel. Experimental Hematology 32: 344–50. doi:10.1016/j.exphem.2004.01.008

Farrell LL, Schoenebeck JJ, Wiener P, Clements DN and Summers KM (2015) The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genetics and Epidemiology 2: 3

Hall EJ, Murphy KF and Darke PGG (2003) Pancreas. In: Notes on Canine Internal Medicine pp 194-197. Blackwell Publishing: Oxford, UK

Hess RS, Kass PH, Shofer FS, Van Winkle TJ and Washabau RJ (1999) Evaluation of Risk Factors for Fatal Acute Pancreatitis in Dogs. Journal of the American Veterinary Medical Association 214: 46-51

Kalli I, Adamama-Moraitou K and Rallis TS (2009) Acute pancreatitis in dogs: a review article. European Journal of Companion Animal Practice 19: 147-155

Kent ACC, Constantino-Casas F, Rusbridge C, Corcoran BM, Carter M, Ledger T and Watson PJ (2016) Prevalence of pancreatic, hepatic and renal microscopic lesions in post-mortem samples from cavalier King Charles spaniels. The Journal of Small Animal Practice 57: 188–93. doi:10.1111/jsap.12444

Newman SJ, Steiner JM, Woosley K, Williams DA and Barton L (2006) Histologic Assessment and Grading of the Exocrine Pancreas in the Dog. Journal of Veterinary Diagnostic Investigation 18: 115–118.

Papa K, Máthé A, Abonyi-Tóth Z, Sterczer A, Psáder R, Hetyey C, Vajdovich P and Vörös K (2011) Occurrence, clinical features and outcome of canine pancreatitis (80 cases). Acta Veterinaria Hungarica 59: 37-52

 

Umemura T, Ota M, Hamano H, Katsuyama Y, Kiyosawa K and Kawa S (2006) Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut 55: 1367–8

Watson P (2012) Chronic pancreatitis in dogs. Topics In Companion Animal Medicine 27: 133–9

Watson PJ (2004) Chronic hepatitis in dogs: a review of current understanding of the aetiology, progression, and treatment. Veterinary Journal 167: 228–41

Watson PJ, Archer J, Roulois AJ, Scase TJ and Herrtage ME (2010) Observational study of 14 cases of chronic pancreatitis in dogs. The Veterinary Record 167: 968–76

Watson PJ, Roulois A, Scase T, Holloway A and Herrtage ME (2011) Characterization of Chronic Pancreatitis in Cavalier King Charles spaniels. Journal of Veterinary Internal Medicine 25: 797–804

Watson PJ, Roulois AJA, Scase T, Johnston PEJ, Thompson H and Herrtage ME (2007) Prevalence and breed distribution of chronic pancreatitis at post-mortem examination in first-opinion dogs. The Journal of Small Animal Practice 48: 609–18

Xenoulis PG, Suchodolski JS and Steiner JM (2008) Chronic pancreatitis in dogs and cats. Compendium of Continuing Education for the Practising

© UFAW 2016


Credit for main photo above:

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