Exocrine Pancreatic Insufficiency

Exocrine Pancreatic Insufficiency

Introduction

The exocrine pancreas plays a central role in the digestion and absorption of nutrients. Pancreatic acinar cells synthesize and secrete enzymes that digest proteins, fats and carbohydrates (protease, lipase and amylase). Pancreatic duct cells furthermore secrete bicarbonate to maintain an optimal pH for digestive and absorptive function, as well as intrinsic factor to facilitate cobalamin absorption.

Exocrine pancreatic insufficiency (EPI) results from deficient synthesis and secretion of pancreatic digestive enzymes. The lack of digestive enzymes in the duodenum leads to maldigestion and malabsorption of intestinal contents. The exocrine pancreas has a large functional reserve capacity and clinical signs of maldigestion do not occur until 90% of secretory capacity is lost.

Diagnosis

Overview

EPI is an uncommon cause of chronic diarrhea in cats; however, in the past it has been under diagnosed due to the lack of specific clinical and laboratory findings. Diagnostic accuracy has now been facilitated by the fTLI test, which is a species specific radioimmunoassay.

Clinical Signs

Clinical signs in affected cats are not specific for EPI: the most commonly reported clinical signs in cats with EPI are weight loss and soft voluminous feces (Steiner & Williams, 2005). Polyphagia despite weight loss is not as commonly seen as in dogs. Many cats also develop a greasy, unkempt hair coat, especially in the perianal and tail regions, resulting from the high fat content of their feces. Some cats have watery diarrhea secondary to intestinal disease. Affected cats may also have a previous history of recurring bouts of acute pancreatitis (e.g., anorexia, lethargy, vomiting) that resulted in chronic pancreatitis and EPI. Concurrent disease of the small intestine, hepatobiliary system and endocrine pancreas may be present.

Differential Diagnosis

The main differential diagnoses for a cat presented with diarrhea, weight loss and changes in appetite are hyperthyroidism, diabetes mellitus and chronic small intestinal disease (most commonly inflammatory bowel disease). Physical examination may help in differentiating these, e.g., by palpating a thyroid nodule or thickened intestinal loops. However, these diseases may be coexisting, especially in older cats, and laboratory testing and imaging (particularly ultrasound) are mandatory.

Laboratory Testing

Routine Laboratory Tests

Results of hematology and serum biochemistries are generally within normal limits or show nonspecific changes. Older cats may have evidence of concurrent renal disease, whereas cats with hyperthyroidism often have increased serum liver enzyme concentrations. Microscopic examination of feces will demonstrate steatorrhea and undigested fat, but this is not pathognomonic for EPI.

Serum concentrations of cobalamin and folate should also be determined in all cats with suspected EPI, because of the common occurrence of low levels (especially for cobalamin) (Steiner & Williams, 1999).

Pancreas-specific Tests

A feline-specific radioimmunoassay for trypsin-like immunoreactivity (fTLI) has now been developed and validated, it is sensitive and the test of choice to diagnose EPI in cats. Fasting serum fTLI concentrations less than 8 μg/L (reference range = 17 - 49 μg/L) are diagnostic for feline EPI (Steiner & Williams, 2000). When the fTLI concentration is between 8 - 17 μg/L, the test should be repeated ensuring adequate fasting; it is also possible the cat has partial EPI that in time may progress to complete EPI. The TLI test is a simple and reliable way of confirming the diagnosis of EPI; however; it is essential to use an assay specific for feline TLI since there is no cross reactivity between canine and feline TLI.

Diagnostic Imaging

Imaging findings are inconsistent; abdominal radiography and ultrasonography generally do not show any abnormalities.

Epidemiology

Risk Factors

Chronic pancreatitis is the most common cause of feline EPI (Figure 26), occurring mainly in mature and older cats. In most cases, it is idiopathic. Rare causes of feline EPI without chronic pancreatitis are pancreatic duct obstruction by liver flukes or pancreatic neoplasia (adenocarcinoma), leading to acinar atrophy. Fecal examination can help in the diagnosis of a fluke infestation, whereas abdominal ultrasonography is essential in detecting a pancreatic mass.

Pancreatic acinar atrophy (PAA) similar to the disease commonly observed in dogs has not been documented in cats.

Figure 26. Chronic pancreatitis is the most common cause of EPI in cats. (© courtesy KW Simpson).

Breed and Sex Predisposition

There is no breed or sex predisposition for the development of EPI in cats.

Pathophysiology

Cats with EPI have an extensive and chronic disease, which is usually due to chronic and irreversible pancreatitis.

The typical signs of EPI (diarrhea, weight loss and polyphagia) are due to decreased intraduodenal concentrations of pancreatic digestive enzymes and bicarbonate with resultant malassimilation of fats, carbohydrates and proteins. This leads to malabsorption, osmotic diarrhea and steatorrhea, and malnutrition. In addition, there are secondary disturbances of intestinal mucosal growth and transport mechanisms that aggravate malabsorption. Cats normally have high numbers of anerobic organisms in their proximal small bowel (Johnston et al., 1993) and it is not known whether they develop changes in the nature and number of small intestinal flora, which is common in dogs with EPI.

Fat malabsorption may result in deficiencies of the fat-soluble vitamins (esp. vitamins K and E). Vitamin K-dependent coagulopathy has been reported in a cat with EPI (Perry et al., 1991) and may occur in other cases as well. Vitamin E deficiency could aggravate oxidative stress, but there are no reports documenting this in feline EPI.

EPI in cats is usually due to chronic pancreatitis, and many cats have concurrent diseases (inflammatory bowel disease, cholangiohepatitis, and diabetes mellitus) that may require additional treatment.

Many cats with EPI have low serum cobalamin concentrations, which impairs their response to treatment. Cobalamin is absorbed in the distal small intestine after it has formed a complex with intrinsic factor, a protein that in cats is exclusively secreted in the pancreatic juice (Fyfe, 1993). The lack of pancreatic intrinsic factor in EPI impacts severely the ability to absorb cobalamin. In addition, concurrent small intestinal disease (Weiss et al., 1996) may further impair cobalamin absorption in cats. Cats seem predisposed to develop markedly reduced serum cobalamin levels under those circumstances (Simpson et al., 2001). Uncorrected cobalamin deficiency may lead to villous atrophy, intestinal inflammation and worsening malabsorption, with resultant failure to respond to pancreatic enzymes alone.

Serum folate concentrations may be decreased in the case of concurrent small intestinal disease resulting in malabsorption of folate. This differs from the situation in canine EPI, where folate levels are often increased due to secondary small intestinal bacterial overgrowth. Cats have however normally high levels of bacteria in their small intestine and bacterial overgrowth is not a recognized syndrome in this species (Johnston et al., 1993; 2001).

Treatment

Enzyme Supplementation

Addition of exogenous pancreatic enzymes to the food is essential for resolution of clinical signs.

Synthetic dried pancreatic extracts are available in several forms.

Powdered pancreatic extracts are most commonly used due to their effectiveness and ease of use. Tablets, capsules and enteric-coated tablets are not recommended since they are usually less effective (Steiner & Williams, 2005). The powdered extract should be mixed within the food immediately prior to feeding (0.5 to 1 tsp per meal twice daily); pre-incubating the enzymes with the food or concurrent antacid therapy are unnecessary (Steiner & Williams, 1999). The amount should be adjusted based on its efficacy in resolving clinical signs; it is common practice to start with the higher dosage, after which it can be gradually decreased to the smallest dose that maintains remission.

Adequate management of cats with clinical EPI depends on long term enzyme replacement and dietary manipulation.

It is important that dietary management and enzyme supplementation are kept constant, since variation and especially the consumption of a non-supplemented meal can cause a return of the diarrhea.

Raw chopped pancreas (30 - 90 g per meal twice daily) may be used as an alternative and can be very effective. It can be stored frozen for at least three months, but is generally less convenient to use and has the potential for causing gastrointestinal infections (e.g., Salmonella, Campylobacter). Bovine pancreas is safest, since there is always a risk of transmitting Aujeszky’s disease when using porcine extracts. Raw chopped pancreas can however be a solution when the cat develops aversion to the powdered extract.

Vitamin Supplementation

Cats with EPI almost always have marked depletion of body cobalamin stores and severely decreased serum cobalamin concentrations. In addition, many cats with EPI have concurrent small intestinal disease which further impairs cobalamin absorption. Supplementation is by parenteral cobalamin (250 - 500 μg/kg subcutaneously every two or three weeks) to maintain normal serum concentrations of cobalamin (Ruaux et al., 2005).

Cats with EPI with or without concurrent small intestinal disease may also have low serum folate concentrations and should be treated with oral folate at 400 μg once daily for 2 - 4 weeks or longer, until serum levels have normalized.

Malabsorption of fat-soluble vitamins (vitamin A, D, E and K) may occur in EPI, although the clinical importance in cats is unknown. Cats with evidence of a coagulopathy should be supplemented with vitamin K. It may also be helpful to increase dietary vitamin E levels because of its antioxidant function, especially in cats that do not respond to enzymes and supportive management alone and especially in cats with concurrent diseases.

Management of Concurrent Diabetes Mellitus

Cats with chronic pancreatitis resulting in EPI as well as diabetes mellitus will need insulin treatment in addition to management of the EPI.

Nutritional Management (Table 10)

High digestibility is a mainstay of dietary management, since it requires less gastric, pancreatic, biliary and intestinal secretions for digestion, and thus facilitates absorption in the upper small intestine. Dietary modification may be required in cats that present with severe weight loss and protein-calorie malnutrition, and also in cats that do not respond adequately to this management.

Cats with EPI should be fed a highly digestible, good quality and energy dense diet, with an appropriate pancreatic enzyme supplement mixed into it (Simpson, 2005). (© C. Hermeline).

Protein

The diet during early refeeding should contain higher protein levels, since many patients with EPI suffer from protein-calorie malnutrition. If response to treatment is poor, concurrent intestinal disease has to be investigated further, e.g., by a dietary trial with an antigen restricted diet. A diet based on rice and soy protein hydrolysate proved to be beneficial in the management of canine EPI (Biourge & Fontaine, 2004). This strategy remains to be validated in cats.

Fat

Fat malabsorption and steatorrhea are major signs in patients with EPI (Williams, 2005). However, fat restriction is of questionable benefit for cats, especially since this species needs a relatively high-fat diet. In addition, there is evidence that higher fat diets promote better digestibility (Suzuki et al., 1999). The cause is unclear, but it may be related to improved preservation of exogenous pancreatic enzymes, particularly lipase. Furthermore, a higher fat and thus more energy dense diet will help an animal in poor body condition to regain its optimal body weight faster. Dietary fat levels can therefore be within the normal range, but high digestibility is essential.

Fiber

Diets containing moderate amounts of fermentable fiber will help to improve GI health by its positive actions upon the mucosal barrier.

Carbohydrate

Cats are poorly adapted to handling carbohydrates, so excessive amounts should be avoided.

Trace Elements and Vitamins

The diet should contain high-normal concentrations of B-vitamins, since body stores are often depleted.

Treatment Failures

Reconfirm EPI

• Make sure the diagnosis is correct, and resubmit an fTLI.
• One should also ensure that serum cobalamin and folate concentrations are managed appropriately.

Inadequate Enzyme Supplementation

Ensure that the enzyme supplement being fed is appropriate (non-enteric coated powder), not outof- date, and fed at the right dose with each meal.

Small Intestinal Disease

Concurrent small intestinal disease may cause continued malabsorption despite adequate enzyme supplementation. Dietary modifications, e.g., to an antigen-restricted or protein hydrolysate diet, can help to evaluate for dietary intolerance/sensitivity. The diet should be fed exclusively, with added enzyme supplementation, for at least two to three weeks. If gastrointestinal signs resolve after the dietary trial, the cat should be challenged with components of its former diet in order to confirm a diagnosis of dietary intolerance/sensitivity.

If dietary modification is not effective, the cat should be investigated for structural intestinal disease (e.g., inflammatory bowel disease) with abdominal ultrasound and endoscopy with intestinal biopsy. Cats with concurrent inflammatory bowel disease usually can be successfully managed with oral prednisolone (Steiner & Williams, 2005).

Conclusion

Feline exocrine pancreatic disease, particularly acute pancreatitis, is more common than previously thought. It however requires a high level of clinical suspicion. Assay of serum fPLI combined with abdominal ultrasound is recommended for the diagnosis of pancreatitis, whereas a severely decreased serum fTLI concentration is diagnostic for EPI in the cat. In both pancreatitis and EPI, concurrent diseases should be assessed and addressed as necessary.

Provision of adequate calories and nutrients is essential in the management of cats with exocrine pancreatic disease. Supportive therapy is important to prevent complications and decrease mortality in acute pancreatitis, and early enteral feeding may be required in order to prevent secondary hepatic lipidosis. Cats with EPI will at least require dietary supplementation with pancreatic enzymes for resolution of clinical signs, and additional treatment with parenteral cobalamin is necessary in many cases.