Nutrition in Disorders of the Exocrine Pancreas in the Dog
The pancreas is a glandular organ located in the cranial abdominal region. The organ is made up of two lobes connected by the body of the pancreas. The right lobe is closely associated with the duodenum and sits within the mesoduodenum. The left lobe begins at the pylorus and extends along the greater curvature of the stomach. (3)
The pancreas has both an endocrine and exocrine function- releasing enzymes from the acinar cells into the digestive tract via the pancreatic duct (exocrine) and production and release of hormones directly into the bloodstream from islet cells (endocrine). (5)
There are two ducts from the pancreas to the duodenum, the pancreatic and the accessory pancreatic duct. The accessory pancreatic duct is the main duct in dogs and opens into the proximal duodenum. In cats, the pancreatic duct is the main duct and merges with the common bile duct prior to reaching the duodenum (3). This alteration between the species accounts for the triaditis syndrome observed in cats.
Disorders of the pancreas can impair both the exocrine and endocrine functions.
The pancreas secretes insulin and glucagon into the bloodstream to regulate glucose metabolism (5).
The acinar cells also produce enzymes including proteases and trypsinogen for digestion of carbohydrates and proteins in the duodenum. The release of bicarbonate and chlorine into the duodenum helps to neutralize acidic contents from the stomach (5). The role of the pancreas is also essential in the absorption of cobalamin, due to pancreatic production of intrinsic factor (6).
Pancreatitis
Pancreatitis refers to inflammation of the pancreas, associated with disruption of the exocrine pancreatic function. Under normal circumstances, proteolytic enzymes are stored in inactive forms in the pancreas and are activated only once they have entered the duodenum (4). Pancreatic acinar cells also produce enzyme inhibitors such as pancreatic secretory trypsin inhibitor.
Pancreatitis develops due to premature activation of enzymes (trypsinogen into trypsin primarily) which leads to localized inflammation, necrosis and autolysis of the pancreatic tissues (4).
Pancreatitis can be classified as acute or chronic, with chronic pancreatitis leading to fibrous changes in the parenchyma (9) and potentially atrophy of the gland. The disease presents with non-specific gastrointestinal signs such as vomiting, abdominal pain and inappetence (5).
In dogs, breed predispositions exist with acute pancreatitis with Miniature Schnauzers and small terriers over-represented (4,5).
Chronic pancreatitis is seen in dogs over the age of five years more frequently than in adolescent animals. Spaniels (Cocker and Cavalier King Charles), Boxers and Collies are over-represented. Concurrent endocrine disease, obesity and hypercalcaemia are also considered risk factors (4).
Clinical signs of pancreatitis are generally non-specific. Abdominal pain, vomiting, anorexia and diarrhoea are often seen (5). Icterus may also be noted, in cases where swelling of the pancreas results in obstruction of the bile duct. Canine pancreatic lipase immunoreactivity (cPLI) is the most specific and sensitive test available. The test has a very high sensitivity; a negative result in a pancreatitis case is highly unlikely (4,8).
Diagnosis of pancreatitis would require invasive sampling and histopathology in order to be definitive. It is rarely performed in human or canine pancreatitis cases as the results rarely change the course of treatment (9). Diagnostic imaging in the form of ultrasonography or serum analysis using the cPLI assay are the most evidence-based diagnostic tools (8). Ultrasonography does rely on the experience and skill of the veterinarian and will vary between individuals.
There is no specific treatment to resolve pancreatitis. Management requires supportive therapy. Intravenous fluids (IVFT) are required in almost every hospitalized case to restore hydration and correct electrolyte imbalance when anorexia and vomiting are the common clinical signs (4). As analgesia will often also be required, IVFT will maintain glomerular filtration rate and excretion of metabolites. Antiemetic medication such as maropitant or ondansetron can be utilized to prevent ongoing fluid losses and anorexia due to feelings of nausea (4).
Whilst fasting has been recommended in the past, there are now known to be several detrimental effects of prolonged fasting. Fasting may be a risk factor in compromise of the gastrointestinal tract- decreased intestinal blood flow and villus atrophy increases the risk of bacterial translocation and sepsis (4).
Parenteral nutrition has limitations in volume and assisted enteral feeding is often a viable, affordable longer-term option. The placement of a feeding tube has become much more common and is now recommended early on in the recovery process (4).
The ideal choice of food for a pancreatitis case is considered to be a highly digestible or predigested, fat-restricted diet. The resting energy requirements are calculated using a formula such as RER= 70 x (BW)0.75. When feeding via tube, a good rule of thumb is to feed 1/3 of the volume on day 1, 2/3 on day 2 and the full volume on day 3. The meals should be divided into 4-6 small meals.
Once the patient is eating voluntarily, management will often continue on an outpatient basis. Medication and ongoing nutrition management will likely be required, with a gradual return to a maintenance diet if no indication of hypertriglyceridaemia or risk of relapse. Small frequent meals (3-4 per day) continue to be recommended. Often a hyper-digestible, restricted fat diet may be required long term (4)- with the Royal Canin Gastrointestinal range, including Gastrointestinal Low Fat indicated for this purpose.
Exocrine Pancreatic Insufficiency
Canine Exocrine Pancreatic Insufficiency (EPI) is a disease of the pancreas which primarily disrupts the exocrine function. EPI will cause maldigestion and malabsorption (2), and affected individuals will often present with weight loss, polyphagia and gastrointestinal signs. Small intestinal diarrhoea is commonly noted, particularly steatorrhoea (6). Abdominal pain may also be a feature of EPI and may cause aggression and nervous behaviour to be reported from the pet owner. A retrospective study covering 178 cases indicated a spectrum of symptoms (1). EPI should remain on a differential diagnoses list even if the classical signs are not observed (1).
EPI is commonly the result of pancreatic acinar atrophy (PAA), but can also occur as the result of chronic, low-grade pancreatitis (6). It is possible to differentiate between the two causes on histological examination- PAA is associated with acinar atrophy and an infiltrate of lymphocytic cells, but no islet loss or evidence of fibrosis is noted (6). Certain breeds such as the Rough Collie, the Chow Chow and the German Shepherd are predisposed to PAA and some studies have indicated a predisposition in females (5,6). An autoimmune mechanism is considered a likely cause of the destruction of the acinar cells. Endocrine pancreatic function is usually not affected, Diabetes Mellitus (DM) is not concurrently seen with EPI due to PAA. Clinical signs are not normally observed until 90% of the acinar function has been depleted (6).
With chronic pancreatitis, more generalized inflammation and fibrosis affecting interstitial, acinar and islet tissues is observed. Diabetes mellitus (DM) can be a consequence of chronic pancreatitis also, and spaniels are over-represented (6). In these cases of chronic pancreatitis, it is sensible to monitor closely for signs of DM or EPI developing.
In cases where the underlying cause is PAA, the clinical signs usually appear before the age of four years. When chronic pancreatitis precedes development of EPI, the age of onset is later, at around 7 years old (6). Some studies have reported EPI to be the most likely extra-gastrointestinal cause of chronic diarrhoea (6).
The test of choice in a diagnostic work up is the measurement of serum TLI (trypsin-like immunoreactivity)(1,6). This test is a direct measurement of exocrine pancreatic function and is a species-specific assay. Levels of trypsin and trypsinogen are measured within the bloodstream and would be decreased in a patient suffering with EPI. The patient should be fasted for 12 hours prior to sampling as levels rise post-prandially. A result of <2.5mg/L is considered positive for EPI, however in breeds suspicious of PAA, there may be a subclinical phase where the level is above this threshold (6).
In patients with chronic pancreatitis and EPI, the test may be harder to interpret. If bouts of acute-on-chronic pancreatitis are present, for example, it is advised to wait until the pancreatitis has been stabilized before trying to measure cTLI (1). cPLI is also decreased in almost all patients with EPI, but there is overlap with healthy individuals, making this a less reliable test for EPI. Serum cobalamin levels should also be measured in individuals with low cTLI, with one retrospective study of 163 dogs with EPI, 82% had hypocobalaminaemia at the time of diagnosis (1).
Treatment for EPI involves a combination of exogenous supplementation of pancreatic enzymes, cobalamin supplementation and nutritional support (6). Pancreatic enzymes, such as Protexin Pro-Enzorb can be given in the form of capsules or coated tablets given with every meal. The coated capsule or tablet provides protection from stomach acid which could denature the enzymes. The dose will need to be adjusted according to the individual’s response.
Hypocobalaminaemia is often a feature of EPI and without correction, will be a negative prognostic factor (1). A recent study in 2017 detailed the efficacy of daily oral supplementation compared to injectable, and within four weeks, all 53 dogs in the trial had serum cobalamin concentrations on or above the reference interval (7). Both oral (Protexin Cobalaplex) and parenteral administration of Vitamin B12 can be considered as viable options in cases of maldigestion and chronic enteropathy. Options based on patient needs and owner compliance should be evaluated on a case-by-case basis.
Pancreatic enzyme supplementation will improve the patients’ ability to digest protein and carbohydrate alongside appropriate nutrition, but fat digestion and absorption will not be affected. The idea behind a low-fat diet in these cases was the theory that unabsorbed fat will be converted in the colon to hydroxy-fatty acids. The presence in the colon will stimulate secretions and decrease faecal consistency (2). Several studies have demonstrated that a moderate fat content in the diet is tolerated well and increases body condition score in patients with EPI (2).
A highly digestible, moderate-calorie, low-fibre diet will be the best choice for these patients and it is impossible to achieve this careful balance with a supermarket maintenance brand. Selected protein or hydrolyzed diets may also work extremely well, particularly in cases where dermatological conditions are also present (2).
It is recommended to consider a food trial in each patient and work on an individual case basis. With each trial, carefully grade the stool quality, quantity and consistency as well as monitoring body weight and condition.
The Gastrointestinal range from Royal Canin is highly digestible, with carefully balanced fibres and a moderate to low fat content depending on the product. This Veterinary Health Nutrition range will offer the clinician the variety of options they need to modify on an individual basis with EPI patients. Hypoallergenic and Anallergenic diets also are highly digestible with less fat restriction, so could be candidates for use when adverse food reactions are suspected. EPI requires lifelong management and can be a devastating and debilitating disease. Response to treatment will vary between individuals, and the ability to tailor the management is essential for success.
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