Interpretation of tyrosin-like immunoreactivity (TLI) values in fasting dogs. Patients with persistently intermediate TLI concentrations are likely to have partial EPI that may progress to complete EPI (Wiberg et al., 1999a; Wiberg & Westermarck 2002)
EPI * Exocrine Pancreatic Insufficiency
managing EPI
The Disease & The Pancreas (updated April 23, 2010)
EPI, Exocrine Pancreatic Insufficiency, is the inability of the pancreas to manufacture and secrete the necessary enzymes required by the body to digest food and absorb nutrients...
...causing the body to starve no matter how much food the dog eats.
One must always be careful when reading medical information on the internet. For this very reason, I have chosen, in this section, not to write in my own words about EPI, but rather to post various published medical research reports from http://www.ivis.org/on EPI from different well-respected researchers to give you, the reader, the most current information and findings on EPI. I have also included earlier research reports so that readers will be able to discern for themselves changes, updates and progress that is being made regarding EPI and to be able to recognize non-current or no longer valid information they may happen upon.
Although this website is dedicated to EPI in Dogs.... now included at the bottom of this page is a section dedicated to EPI in Cats too!
---------------------------------------------------------------------------------------------------------------------------
Proceedings of the 33rd World Small - Animal Veterinary Congress - Dublin, Ireland - 2008
http://www.ivis.org/
How I Treat - Exocrine Pancreatic Insufficiency
Jörg M. Steiner Dr.med.vet., PhD, DACVIM, DECVIM-CA
Gastrointestinal Laboratory, Dept.VSCS, College of Veterinary Medicine and Biomedical Sciences, Texas A&M
University, 4474 TAMU College Station, TX 77843-4474, USA
Enzyme supplementation
Most dogs and cats with EPI can be successfully treated by dietary supplementation with pancreatic enzymes. Dried extracts of bovine or porcine pancreas are available e.g. Viokase or Pancrezyme). The clinical impression in dogs and ats that powder is more effective
than tablets, capsules, and especially enteric-coated products has also been substantiated in human patients with EPI. Initially, two teaspoons per 20kg body weight and meal should be given in dogs and one teaspoon per cat and meal in cats. Oral bleeding has recently been reported in 3 of 25 dogs with EPI treated with pancreatic enzyme supplements.1 The oral bleeding stopped in all 3 dogs after the dose of pancreatic enzymes was decreased. Moistening the food pancreatic/powder mix also appears to decrease the frequency of this side effect. If the owner has access to fresh pancreas this may be a viable alternative to use of pancreatic powder. However, there is a slight risk of transmission of Aujeszky’s disease from raw pork pancreas, BSE from raw bovine pancreas, and Echinococcus from raw game pancreas. One to three ounces (30-90 g) of raw chopped pancreas can replace one teaspoon of pancreatic extract. Raw bovine pancreas can be kept frozen for several months without loss of enzymatic activity. Preincubation of the food with pancreatic enzymes, supplementation with bile salts, or concurrent antacid therapy are unnecessary in most canine and feline patients with EPI. When clinical signs have resolved the amount of pancreatic enzymes given can be gradually decreased to the lowest effective dose, which may vary from patient to patient, and from batch to batch of the pancreatic supplement. Even though pancreatic enzyme supplementation causes the clinical signs to subside in almost all patients, it has been shown in human beings and dogs with EPI that nutrient absorption, and particularly fat absorption are not normalized by enzyme supplementation. This is thought to be due to the low pH in the stomach leading to irreversible damage of the pancreatic lipase contained in the supplement. Even though gastric pH can be raised by administration of antacids, the negative effect of the increased intraluminal gastric pH on fat digestion by gastric lipase appears to cancel much of the positive effect, so that overall there is only a minimal increase in fat absorption, which is clinically not important in most patients. However, the use of omeprazole has recently been shown to be efficacious in human patients with EPI and may be tried if the patient does not respond to routine therapy.
Dietary considerations
Some authors have suggested feeding low fat diets in order to accommodate impaired fat digestion. However, this may even further decrease fat assimilation and may
potentially lead to serious complications associated with hypovitaminoses of fat-soluble vitamins and conditions associated with a lack of essential fatty acids. Some types of dietary fiber interfere with pancreatic enzyme activity. Therefore, a diet low in insoluble or non-fermentable fiber should be fed.
Vitamin supplementation
Response to enzyme supplementation alone may not be satisfactory in some canine or feline patients with EPI. This is not surprising if one considers that many dogs
and especially cats with EPI also have a serious depletion of total body cobalamin stores. Serum cobalamin and folate concentrations should be routinely evaluated in
small animals with suspected EPI, and dogs and cats with severely decreased serum cobalamin concentrations should be treated with cobalamin parenterally. Even
though hypovitaminoses of other vitamins, especially vitamin K, are not very common, they have been reported in some cats with EPI and should be anticipated as
potential complications. Patients that do not respond to therapy Some dogs and cats do not respond to enzyme supplementation and cobalamin application. These
patients likely have concurrent small intestinal disease. In dogs with EPI small intestinal bacterial overgrowth is common and may need to be treated with antibiotic
therapy. In cats with EPI inflammatory bowel disease can occur concurrently.
Prognosis
EPI is associated with an irreversible loss of pancreatic acinar tissue in most cases, and complete recovery is therefore extremely rare. However, with appropriate
management and monitoring these patients usually gain weight quickly, pass normal stools, and can go on to live a normal life for a normal life span. Reference
1. Rutz GM, Steiner JM, Williams DA (2002) Available on request from author.
Reprinted in IVIS with the permission of the Congress Organizers
Proceedings of the 33rd World Small Animal Veterinary Congress 2008
---------------------------------------------------------------------------------------------------------------------------------------
In: Encyclopedia of Canine Clinical Nutrition, Pibot P., Biourge V. and Elliott D.A. (Eds.). International Veterinary Information Service, Ithaca NY http://www.ivis.org/, Last updated: 11-Feb-2008; A4205.0208 Dysfunction of the exocrine pancreas is broadly characterized by the loss of functional pancreatic mass (exocrine pancreatic insufficiency), or inflammation (pancreatitis), with consequent diarrhea and weight loss, or abdominal pain and vomiting respectively. This chapter will outline the role of nutrition in the pathogenesis and management of exocrine pancreatic disease in the dog. Kenneth W. SIMPSON A diagnosis of exocrine pancreatic insufficiency (EPI) is made on the basis of compatible historical and clinical findings nd by ruling out infectious, parasitic, metabolic, and anatomic causes of small bowel diarrhea and weight loss. The diagnosis is confirmed by demonstrating a subnormal serum concentration of trypsin-like immunoreactivity (TLI), recently reviewed by Westermarck & Wiberg (2003). Dogs with EPI usually present for investigation of chronic diarrhea (feces of large volume and cow-pat consistency, often yellow to grey in color) and weight loss (mild to extreme), which is often associated with a ravenous appetite. Pica and coprophagia are also common. A poor hair-coat (hair loss, eczema, dryness, scurf) polydipsia and marked muscle loss are observed in some dogs. The feces of canine pancreatic insufficiency patients are often of large volume and cowpat consistency, and are discolored and highly pungent. (© M. Weber). Polyuria and polydipsia may be present when exocrine pancreatic insufficiency caused by chronic pancreatitis is complicated by diabetes mellitus. Acute abdomen due to mesenteric torsion has also been associated with EPI. Routine hematology and biochemistry are fairly unremarkable in dogs with EPI. Modest increases in alanine amino-transferase (ALT) and a decrease in cholesterol are observed in some dogs. Pan-hypoproteinemia is not a feature of EPI, and its presence suggests that primary small intestinal disease is causing the diarrhea and weight loss, rather than EPI. The presence of hyperglycemia and glucosuria in dogs with signs of EPI should prompt consideration of diabetes mellitus secondary to chronic pancreatitis, or pancreatic hypoplasia. Serum concentrations of cobalamin (Vitamin B12) and Vitamins A and E can also be markedly reduced in dogs with EPI. In contrast, serum folate concentration is often increased. Serum concentrations of zinc and copper are decreased in dogs with experimental pancreatic insufficiency, whereas serum iron and transferrin saturation are increased. The specific diagnosis of EPI is made by demonstrating a subnormal concentration of trypsin-like immunoreactivity (TLI) in a fasted serum sample (Williams & Batt 1988). Serum TLI is considered to originate solely from the pancreas and is an indicator of pancreatic mass and inflammtion (Simpson et al 1991) In dogs with EPI caused by atrophy or chronic inflammation the amount of TLI leaking from the pancreas into the circulation is reduced, and a subnormal TLI concentration can be demonstrated The TLI test is a simple and reliable way of confirming a diagnosis of EPI. However, if the TLI test result does not fit the patient's clinical signs it is prudent to rerun the test after ensuring an overnight fast to rule out sampling/handling/technician error. The TLI test will not detect conditions that may cause the intra-luminal destruction of pancreatic enzymes e.g., hyperacidic states such as gastrinoma and mast cell tumor, but these conditions have other diagnostic features such as hematemesis and esophagitis to distinguish then from primary EPI. EPI must be distinguished from primary intestinal disease. Frequency distribution of age at diagnosis of canine exocrine pancreatic insufficiency in 199 german shepherd dogs and 102 dogs of other breeds. Frequency distribution of breeds for 301 cases of canine pancreatic insufficiency. The presence of large bowel diarrhea, frequent vomiting, pallor, jaundice, edema or ascites should prompt consideration of other more likely diagnoses. Hypoproteinemia is not a feature of uncomplicated EPI and usually indicates a protein losing enteropathy. Do not rely solely on the TLI test result without other supportive evidence of exocrine pancreatic disease. The differential diagnosis of EPI includes other causes of small bowel diarrhea and weight loss Pancreatic acinar atrophy (PAA) is probably the most common cause of exocrine pancreatic insufficiency (EPI) in the dog. Dogs under five years of age diagnosed with EPI are usually suspected of having pancreatic acinar atrophy, whereas older dogs likely have a higher incidence of pancreatitis induced degeneration (Hall et al.,1991). Dogs with chronic relapsing pancreatitis are considered at increased risk of developing EPI. Many different breeds have been diagnosed with EPI . A familial predisposition to pancreatic acinar atrophy has been reported in German Shepherd Dogs, Collies and English Setters (Westermarck 1980; Boari et al 1994; Moeller et al 2002; Wiberg 2004). As it is impossible to determine the cause of atrophy in an end stage pancreas, prospective studies of the development of canine PAA have been conducted. These longitudinal studies have identified German Shepherd dogs and Rough Coated Collies with sub-clinical exocrine pancreatic insufficiency, detected by assay of circulating TLI, in whom pancreatic atrophy is preceded by a marked lymphocytic infiltration Westermarck et al 1993a; Wiberg wet al 1999b, 2000). This strongly suggests an autoimmune basis for PAA. There is no evidence that a lack of trophic factors e.g., CCK, or anti-pancreatic antibodies play a role in the genesis of PAA. Breeds such as Miniature Schnauzers appear to be overrepresented with relapsing pancreatitis and may be predisposed to EPI. Exocrine pancreatic insufficiency (EPI) in the dog is most often a consequence of a severe reduction of pancreatic mass caused by pancreatic acinar atrophy, or chronic pancreatitis Photographs of EPI due to pancratic acinar and chronic atrophy and chronic pancreatitis. Chronic pancreatitis. Fibrosis and atrophy are evident in this section from the pancreas of a dog with EPI secondary to pancreatitis (x10; H&E coloration). Photographs of EPI due to pancratic acinar and chronic atrophy and chronic pancreatitis. Lymphocytic inflammation precedes the development of EPI in dogs with familial acinar atrophy (x40; H&E coloration). Photographs of EPI due to pancratic acinar and chronic atrophy and chronic pancreatitis. Islet cells, stained for insulin (brown), and surrounded by a sea of atrophied exocrine tissue are relatively normal in dogs with EPI. (Glucose tolerance is abnormal but responds to enzyme supplementation - see text for details) (x20; immunocoloration for insulin). Pancreatic hypoplasia with concomitant EPI and diabetes mellitus has been rarely documented. In theory, EPI can also occur secondary to: Extensive loss of exocrine pancreatic mass (approx. 90%), whether by atrophy or chronic inflammation is required before signs of EPI are evident Simpson et al 1992 The predominant clinical signs of EPI, diarrhea, weight loss and a ravenous appetite can be directly attributed to decreased intra-duodenal concentrations of pancreatic enzymes, bicarbonate, and various other factors with resultant malassimilation of fats, carbohydrates and proteins Pathophysiology of exocrine pancreatic insufficiency. Malabsorption of fat soluble vitamins and cobalamin, and changes in the number and composition of the small intestinal bacterial flora have also been documented in dogs with EPI and may contribute to their clinical condition (Williams et al 1987; Westermarck et al 1993b; Adamama-Moraitou et al 2002) . Subnormal serum concentrations of cobalamin are frequently documented (approximately 75% of cases) in dogs with EPI and are likely a consequence of intrinsic factor deficiency, disrupted binding of cobalamin to IF (by intestinal pH, lack of proteases) and bacterial consumption of cobalamin (Batt et al 1989; Simpson et al 1989a; Simpson et al 1993) . Following ingestion, cobalamin is released from food in the stomach. It is then bound to a non-specific cobalamin-binding protein of salivary and gastric origin called haptocorrin. Intrinsic factor (IF), a cobalamin binding protein that promotes cobalamin absorption in the ileum, is produced by the stomach and pancreas in dogs. The affinity of cobalamin for haptocorrin is higher at acid pH than for IF, so most is bound to haptocorrin in the stomach. Upon entering the duodenum haptocorrin is degraded by pancreatic proteases, and cobalaminis transferred from haptocorrin to IF, a process facilitated by the high affinity of IF for cobalamin at neutral pH. Cobalamin-IF complexes traverse the intestine until they bind to specific receptors (previously called IFCR, but recently dubbed cubilin) located in the microvillus pits of the apical brush-border membrane of ileal enterocytes. Cobalamin is then transcytosed to the portal bloodstream and binds to a protein called transcobalamin 2 (TC II), which mediates cobalamin absorption by target cells. A portion of cobalamin taken up by hepatocytes is rapidly (within an hour in the dog) re-excreted in bilebound to haptocorrin. Cobalamin of hepatobiliary origin, in common with dietary derived cobalamin, under goes transfer to IF and receptor mediated absorption, thus establishing enterohepatic recirculation of the vitamin. Low serum cobalamin concentrations in dogs have been associated with exocrine pancreatic insufficiency (EPI), severe intestinal disease, IF-Cbl receptor abnormalities, and conditions associated with the proliferation of enteric abacteria e.g stagnant loops. Cobalamin absorption in the dog. Other abnormalities encountered in dogs with EPI include alterations in: Trace element status in EPI has received relatively little study. One report of German Shepherd dogs with EPI indicates normal serum concentrations of copper and zinc. However, it has been recently demonstrated that serum copper and zinc decline, and serum iron and transferrin saturation increase, after pancreatic duct ligation (Adamama-Moraitou et al 2001) The clinical significance of these abnormalities is unclear. The severe malassimilation of nutrients in EPI can lead to protein calorie malnutrition that may further compromise residual pancreatic function, intestinal absorption and metabolic homeostasis. Dermatological abnormalities are variably present in German Shepherd dogs with EPI and their presence may be related to protein calorie malnutrition, deficiencies in trace elements and minerals and potentially adverse reactions to food. An enzyme preparation must be given at mealtimes in situations of insufficient enzyme secretion by the exocrine pancreas. There are many variations of powdered porcine enzymes, and/or appropriate enteric preparations that are now available. Please view http://www.epi4dogs.com/enzymesdigestion.htm for the list. Also feeding fresh pancreas is another alternative. The enzyme supplement should be mixed into the food. Pre-incubation does not "significantly" impact outcome (Pidgeon & Strombeck 1982) However, many folks claim that their dog only did better when the enzymes are incubated in room temperature food for approximately 20 minutes. A new batch, change of preparation or increased amounts may produce a response. If cessation of diarrhea and weight gain are observed over a two week period the animal is maintained on this regimen and an attempt is made to decrease the enzyme supplement to the lowest effective dose. If the therapy fails, the lot or the mode of presentation may be changed, or the enzyme quantities increased. If a response is not being achieved with a dose of 0.4 g/kg of non-enteric coated powdered extract or 3 g/kg body weight/meal whole pancreas, inadequate enzyme replacement is an unlikely reason for treatment failure. Fat soluble vitamins are likely candidates for malabsorption, and low levels of Vitamins A and E have been reported in German Shepherd dogs with EPI. Vitamin E can be given orally (400 500 IU SID q 1 month). It seems prudent to examine the vitamin K status of dogs with EPI who have laboratory evidence of a coagulopathy (bleeding). Cobalamin deficiency can have a myriad of effects on the body and the provision of supplementary parenteral cobalamin (cyanocobalamin, vitamin B12) is recommended because pancreatic enzyme supplementation does not reverse the deficiency. Studies in dogs indicate that the parenteral administration of a single dose of cyanocobalamin (250 - 500 µg SQ once per month) is enough to prevent recurrence of metabolic abnormalities for up to one month. Please read the B12 section: Role of vitamin B12 in the organism. Vitamin B12 plays a fundamental role in protein synthesis and red blood cell production and has an enzyme function in many essential biochemical reactions. Feeding Dogs with EPI The pivotal role of the exocrine pancreas in the digestion and assimilation of nutrients would suggest that EPI is a disease that would be particularly amenable to nutritional intervention. In "theory" a highly digestible, fat restricted diet (fat is considered the most difficult nutrient to assimilate and lipase activity is the limiting step in its digestion) that is low in fiber (fiber is indigestible, lowers energy density and hinders pancreatic enzyme activity) would seem justified in dogs with EPI. However, analysis of the outcome (survival) of 116 dogs with EPI indicates that dogs that received a modified diet (n=73, 30% dead) did not outlive those receiving a standard diet (n=43, 35% dead) (Hall et al 1991) ...Please read below on "Potential Advantages of a High Fat Content" because more recent additional research has proven fat restriction may not be the best treatment. A 50% reduction of the initial dose is possible in the majority of the dogs (after stabilization is achieved) (Simpson et al 1994) (This adaptation of the dose is important, because the cost of pancreatic enzymes is an obstacle to treatment for many owners, who prefer to euthanize their dogs. In complete contrast to the paradigm of fat restriction in EPI, diets with 43% calories from fat have been shown to promote better protein, fat and carbohydrate digestibility compared to diets containing 18 and 27% calories from fat in dogs with experimental EPI (Suzuki et al 1999). Improved preservation of exogenous pancreatic enzymes, especially lipase, could explain this observation. It is of note that studies in dogs with experimental exocrine pancreatic insufficiency demonstrated that fecal fat output is more dependant on the digestibility of the fat, rather than the amount fed (Pidgeon 1982; Pidgeon & Strombeck 1982) A case report of 3 German Shepherd dogs with EPI and poor haircoat demonstrated that a 19% fat DM (40.8 % of calories from fat), soy protein isolate hydrolysate and rice diet was well tolerated and improved fecal quality, haircoat and weight gain (2 - 10 kg) compared with the dogs previous diets. The dogs recovered optimal body condition within a 2-month period (Biourge & Fontaine 2004) These observations suggest that high fat, highly digestible diets are not contra-indicated in the management of EPI. Traditionally, dietary supplementation with medium chain triglyceride oil (24 mL/meal) has been considered a beneficial way of providing calories to severely malnourished patients fed a highly digestible fat restricted diet but supportive data are lacking. However feeding a higher fat and thus more energy dense diet could promote a rapid restoration of optimal body weight without recourse to medium chain triglyceride oil. As the importance of nutritional modification in the management of EPI is far from clear, and the costs associated with special diets are a common reason for euthanasia this author recommends initially feeding a good quality maintenance dog food (i.e., high digestibility) with an appropriate exogenous enzyme supplement mixed into it. If the response to treatment is poor then dietary modification is an option (see treatment failure - below). This is probably the number one cause of treatment failure. Some dogs develop an aversion to the enzyme supplement and raw pancreas may have to be used (or enteric coated capsules of enzymes such as CREON, recently approved by the FDA), if attempts to disguise the powder are unsuccessful. Stomatitis has been reported as a side effect of exogenous enzyme supplementation and may be remedied by decreasing the supplement by 50% (Rutz et al 2002). Decreasing the enzyme supplement may also be considered in the majority of dogs with EPI. EPI may impact the quantity and composition of the small intestinal flora and compromise the host response to a normal or abnormal flora. These alterations are usually addressed by treatment with an enzyme supplement. However, in some patients, diarrhea cannot be eliminated until antibiotics are administered. In these patients treatment failure may reflect decreased synthesis of intestinal mucosal enzymes associated with EPI. The presence of an abnormal flora cannot be predicted accurately by measuring serum concentrations of cobalamin and folate, so a trial with an antibiotic such as oxytetracycline (20 mg/kg PO TID 28d), ortylosin (10 mg/kg PO TID) can be undertaken. Benefits of dietary modification in dogs (n=14) fed a "moderate fat, highly digestible low fiber diet" for four weeks versus a maintenance diet were restricted to a tendency (8/14 dogs) to reduced borborygmi, flatulence and fecal volume (Westermarck et al, 1990). A study in 21 EPI dogs, evaluating the benefit of feeding a low fat (13% of calories), low fiber diet compared to the usual commercial or home cooked diet failed to show any significant benefit of severe fat restriction (Westermarck et al 1995) Finally, feeding a low fat (13% of calories) diet in combination with exogenous enzymes (2.5 g/300 g food) to dogs (n=20) has been shown to promote a 24% average weight gain over a four month period, and a good response in 17/20 dogs (Simpson et al 1994.) However, the role of the diet in this study is unclear as 11/20 dogs were subsequently successfully maintained on a variety of diets after the trial period. Routine hematology and biochemistry are almost always normal in uncomplicated EPI, so abnormalities such as hypoproteinemia (which may indicate a protein losing enteropathy) should be pursued. Once these common reasons for treatment failure (inadequate enzyme supplementation, the presence of bacterial overgrowth or intolerance, and concomitant small intestinal disease) have been addressed, nutritional modification must be considered. Dietary management of small intestinal disease is typically based on feeding a highly digestible, usually a rice based diet that is restricted in fat.However, rice is a grain and tends to disagree with most (but not all) EPI dogs.There are now many grain-free foods available that are much more suited to an EPI dog. If dietary sensitivity is suspected an antigen restricted or protein hydrolysate diet (prescription diet) may be employed. Hydrolysates are produced by enzymatic proteolysis of native proteins which results in an array of peptides that are small enough so that they may not be recognized by, nor trigger a reaction by the immune system (Guilford 1996). These peptides are also highly digestible, therefore reducing their retention time in the lumen of the intestine. Soy hydrolysates have been used extensively in the prevention of food sensitivity in babies and in calves (Lalles et al 1995; Terracciano et al 2002). If gastrointestinal signs resolve after the dietary trial (usually one to two weeks) it is necessary to rechallenge the individual with the original diet to confirm a diagnosis of dietary intolerance. The addition of specific antigens such as beef, soy, chicken to the diet that induced remission is required to document hypersensitivity. It is of interest that the use of a soy hydrolysate diet with relatively high fat content was effective in facilitating weight gain, decreasing diarrhea and improving haircoat in three dogs with EPI that had failed to respond to diet and pancreatic extracts( Biourge & Fontaine 2004) German Shepherd suffering from exocrine pancreatic insufficiency. If response to treatment is still poor then acid suppression to protect pancreatic enzymes and empirical dietary modifications can be made, while carefully reviewing the diagnosis of EPI and considering other underlying disorders.Please review this website's diet section http://www.epi4dogs.com/diet.htm Dogs with confirmed EPI that respond poorly to appropriate enzyme supplementation and antimicrobial therapy usually require investigation of the small intestine. In a majority of dogs suffering from EPI a high quality maintenance diet supplemented with powdered pancreatic enzymes resolves most of the abnormalities associated with the disease. The relatively high cost of enzyme supplementation and special diets can significantly impact the outcome, precipitating euthanasia. If pancreatitis or diabetes is associated, prognosis is more reserved. The Role of Nutrition in the Pathogenesis and the Management of Exocrine Pancreatic Disorders
By: K. W. Simpson
College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
BVM&S, PhD, MRCVS, Dipl ACVIM, Dipl ECVIM-CA
Dr. Simpson graduated from the University of Edinburgh (BVM&S) in 1984. His PhD (University of Leicester, 1988) focused on pancreatic and intestinal function in dogs, and was followed by clinical training at the University of Pennsylvania, and the Ohio State University. He is presently an Associate Professor of Medicine at Cornell University with clinical and research interests in internal medicine and gastroenterology.1. Exocrine Pancreatic Insufficiency
Diagnosis
Overview
Signs
Supplementary Tests
Clinicopathological Tests
Specific Diagnosis
Diagnostic Pitfalls
The combination of diarrhea, weight loss, ravenous appetite, and relatively normal laboratory findings, often in a breed that is predisposed (e.g., German Shepherd) The following two figures strongly suggests EPI is a likely cause.
Decision Tree
Table 2. Differential Diagnosis of Chronic Small Bowell Diarrhea Infectious Giardia, Histoplasmosis, pathogenic bacteria (Salmonella, Campylobacter), Phycomycoses, Mycobacteria Metabolic Hypoadrenocorticism, liver disease, kidney disease Dietary Intolerance / Allergy Exocrine pancreatic insufficiency Primary or secondary Small intestinal disease Structural Partial obstruction : intussusception, foreign object, neoplasia, lymphangiectasia, congenital anomalies Inflammatory Eosinophilic, lymphoplasmacytic, granulomatous Neoplastic Lymphosarcoma, adenocarcinoma, leiomyoma, fibrosarcoma Bacterial overgrowth Secondary, idiopathic Functional Motility disorders, idiopathic Epidemiology
Risk Factors
Breed Predispositions
Pathophysiological Mechanisms of EPI
EPI Case Study - Neutered Female Boxer Age 7 Years
History and Clinical Examination Stat Blood Tests Packed cell volume 39% Total Protein 7.5 g/dL Blood urea nitrogen 30 - 40 mg/dL Glucose 86 mg/dL Complete Blood Count Profile PCV (%) 44 (42 - 57) Albumin (g/dL) 3.9 (3.1 - 4.1) MCV (fl) 74 (63 - 74) Globulin (g/dL) 3.0 (1.9 - 3.6) WBC (thou/µL) 8.1 (6.2 - 14.4) ALP (IU/L) 1130 (12 - 122) Neutrophilis (thou/µL) 6.6 (3.4 - 9.7) ALT (IU/L) 357 (25 - 106) Lymphocytes (thou/µL) 1.4 (1.3 - 4.7) GGT (IU/L) 33 (0 - 10) Platelets (thou/µL) 475 (179 - 483) Cholesterol (mg/dL) 106 (124 - 335) Histopathology 
Pancreas: Atrophy with lymphoplasmacytic inflammation, still residual acinar tissue fibrosis
Liver: Vacuolar hepatopathy - multifocal, clusters
Stomach: Moderate lymphoplasmocytic infiltrate lymphoid nodules in deep lamina propria; +++helicobacter organisms
Duodenum/jejunum/ileum: Peyers patches sampled
Mesenteric lymph node: HyperplasiaUrinalysis Fecal USG 1.041 Giardia ELISA negative, zinc sulphate negative. Many Clostridium perfringens- like organisms on a smear pH 6.5 TLI 5.58 µg/L (5 - 25) protein ++ (meaningless because of the urine specific gravity) Cobalamin 184 pg/mL (175 - 550) Folate 27 ng/mL (4 - 13) Ultrasound: Questionable diffuse hyperechoic liver Thoracic radiographs: Normal Cutaneous aspirates: Blood Coagulation tests: Normal (OSPT, APTT) Working Diagnosis After Surgery Exocrine pancreatic insufficiency, possible Helicobacter related gastritis, reactive lymphadenopathy presumed secondary to gastrointestinal disease.
Over the next two months the dog gained 10lbs (42# to 52#), fecal consistency normalized and the energy level of the dog increased.Interpretation Chronic diarrhea, weight loss and polyphagia suggestive of maldigestion or malabsorption. Elevated liver enzymes suggest a primary or secondary hepatopathy in response to exogenous corticoteroids or GI disease. Low cholesterol suggests small intestinal disease, EPI or liver disease. Lack of other evidence of hepatic synthetic failure (normal protein, BUN) suggests low cholesterol may be due to GI disease or EPI.
Normal TLI test lowers the likelihood of EPI suggesting that high folate and low normal cobalamin are due to intestinal disease. Due to the degree of weight loss and lack of a definitive diagnosis an exploratory laparotomy was performed to biopsy the gastrointestinal tract, liver and mesenteric lymph nodes.
At surgery a 10 cm tangled cloth in the stomach and a 6cm cloth in the jejunum were found. These were considered incidental as they were not causing obstruction and likely secondary to the polyphagia. A thickened gastric wall and severe atrophy of the pancreas were observed.Commentary The history of marked weight loss, diarrhea and polyphagia coupled with normal serum protein but low cholesterol are typical for EPI. The increases in liver enzymes, particularly ALP are higher than might be anticipated in EPI, but the prior steroid treatment and intestinal foreign bodies may have contributed to these changes. The changes in cobalamin and folate are suggestive of EPI or a blind loop syndrome.
No obstruction was visualized by ultrasound or at surgery, so the changes in cobalamin and folate are likely a consequence of EPI. However the TLI test result at 5.28 argued strongly against EPI. Usually dogs with signs of EPI have TLI < 2.5. In this case histology confirmed atrophy secondary to lymphocytic infiltration. Perhaps the small amount of inflammation in the residual pancreatic tissue was enough to keep the TLI in the normal range while exocrine secretion was severely impaired. Unfortunately the owner declined further TLI tests to further investigate the normal TLI.Treatment
Enzyme Supplement (additional information/ updates from website owner, not author of this article, is printed in red)
Micronutrients
http://www.epi4dogs.com/b12.htm there is a recommended protocol now for B12 treatment one injection weekly for 6 weeks, one injection bi weekly for 6 weeks and then injection monthly and test to verify that monthly holds the dog's B12 levels. Recently there have even been cases of EPI dogs being managed with a combination of certain B12 pills and Injections. again, please review the B12 section on this website. The cobalamin malabsorption does not resolve after enzyme supplementation and lifelong therapy is recommended. 
Potential Advantages of a High Fat Content
Treatment Failures
Inadequate Enzyme Supplementation
Bacterial Overgrowth/intolerance
Small Intestinal Disease
Dietary Modifications
Conclusion/prognosis
References
...as adapted from http://www.veterinarypartner.com/Content.plx?P=A&A=1627&S=1&SourceID=42
__________________________________________________________________________________________________
Proceeding of the NAVC - North American Veterinary Conference- Jan. 8-12, 2005, Orlando, Florida
http://www.ivis.org/
NEW DEVELOPMENTS IN THE DIETARY
MANAGEMENT OF EXOCRINE PANCREATIC
INSUFFICIENCY
Denise A. Elliott, BVSc, PhD, Dipl ACVIM, Dipl ACVN
Royal Canin USA, Inc
St Charles, MO
INTRODUCTION
Exocrine pancreatic insufficiency (EPI) is a clinical syndrome that arises secondary to a deficiency of pancreatic enzymes. The predominate cause of EPI is an immune
mediated, lympocytic pancreatic acinar atropy. Less common causes include pancreatitis and neoplasia. In these situations, concurrent diabetes mellitus may also be
observed. EPI typically affects young dogs, 1-5 years of age, with reported breed dispositions including the German Shepard, Rough Collie, English and Irish Setters. Clinical signs are the result of nutrient malabsorption secondary to failure of intraluminal digestion. Although the digestion of protein and carbohydrate will be affected, the digestion of fat is most severely impaired since lipases are absent from the normal array of intestinal brush border enzymes. Studies have suggested that 70% of dogs with EPI have concurrent small intestinal bacterial overgrowth (SIBO) and secondary damage to the small intestine. Bacteria in the intestinal tract can metabolize undigested fat to hydroxy-fatty acids which can lead to secretory diarrhea in the largeintestine. Bacteria also deconjugate bile acids further impairing fat digestion and absorption. Some dogs will also exhibit reduced duodenal enzyme activity. This can arise because of SIBO, or as a result of generalized cachexia. The clinical signs of EPI include severe weight loss (cachexia), large, voluminous pale feces, ravenous appetite, copraphagia, borborygmus, abdominal discomfort, poor skin and haircoat. Diagnosis is confirmed by a serum TLI concentration less than 2.5 μg/L in the dog, and < 9 μg/L in the cat. Recently, it has been shown that measurement of serum TLI can be utilized to diagnose subclinical EPI, beforethe onset of clinical signs of severe pancreatic loss. Subclinical EPI is suspected in dogs with repeatedly low
serum c TLI concentrations (< 5.0 μg/L) but no clinical signs of EPI. Measurement of vitamin B12 (cobalamin) and folate is also useful in patients with EPI. A diagnosis of concurrent smallintestinal bacterial overgrowth is supported by an elevated folate and low vitamin B12 concentrations.
MANAGEMENT
Client understanding and compliance are key to successful therapeutic management. The client should be informed that several weeks to months maybe required for the therapeutic response to occur, and therapy is life-long. Dietary management in conjunction with pancreatic enzyme supplementation is the cornerstone of management. The amount of food to feed the EPI patient should be calculated on the current body weight. Once the maldigestion and malabsorption are controlled with concurrent enzyme therapy, the amount fed can be gradually increased to facilitate weight gain. The food should be offered in at least two meals per day.
Since fat is the most difficult nutrient to digest, requiring the interplay between the intestine, liver and pancreas, fat digestion is most severely affected by pancreatic enzymedeficiency. Therefore, it is intuitive that a highly digestible, low fat diet is appropriate for the management of exocrine pancreatic insufficiency. However, what constitutes a restricted fat diet varies considerably among manufacturers. Nutritionists consider a restricted fat diet to be one that contains less than 18% of the energy from fat. Using this recommendation, it is clear that many diets formulated for the management of gastrointestinal disease are not actually low fat diets.
Simpson et al evaluated the effect of a low fat diet in conjunction with enzyme supplementation in the management of 20 dogs with exocrine pancreatic insufficiency. Clinical signs resolved in all 20 dogs within 4 months of instituting therapy. The body weight of the dogs increased on average by 24%. Long term contact was available for 17 of 20 dogs. Eleven of these dogs were progressing well, 3 were euthanized for poor progress, and 3 were euthanized for unrelated reasons. Once the dogs were stabilized, they required 6-58% less enzyme supplementation compared tothe initial dose needed for stabilization. A study by Westermarck et al failed to demonstrate a benefit of severe dietary fat restriction in 21 dogs with naturally occurring EPI. However, there was considerable variation between dogs in this study. Suzuki et al reported that dogs with experimental EPI tolerated a diet consisting of 43% fat (ME basis). The dogs in this study absorbed protein, fat and carbohydrate more effectively compared to when they were fed diets with 18 and 27% of the calories from fat. The improved digestibility was attributed to preservation of theexogenous pancreatic enzymes, particularly lipase, in the higher fat diets. Medium chain triglyerides, which contain 8-12 carbons,
have been recommended by some authors. It has been suggested that MCT’s are less dependent on micelle formation and the lymphatic vasculature for digestion and absorption. It has been suggested that MCT’s reduce the palatability of the diet. In addition, MCT’s have been associated with the development of hepatic lipidosis in cats. Dietary fiber can interfere with the effect of pancreatic enzymes. Dutta et al evaluated the effect of high dietary fiber in twelve human patients with EPI. The high fiber diet (28.75 g TDF/1000 kcal) was associated with an increase in fecal weight, fecal fat excretion and flatulence. In vitro studies using different concentrations of cellulose, pectin, and wheat bran incubated with amylase, lipase, and trypsin demonstrated that increasing the dietary fiber concentration
reduced pancreatic enzyme activity.Maldigestion of fat may result in malabsorption of the fat soluble vitamins. Indeed, very low concentrations of tocopherols and vitamin K coagulopathies have been reported in patients with EPI. Therefore the diet should contain adequate fat soluble vitamins. Additional subcutaneous
supplementation with vitamin K may be necessary in some patients. Malabsorption of cobalamin can occur from a combination of decreased availability of pancreatic intrinsic factor and pancreatic proteases necessary to release cobalamin from R proteins, coupled with overgrowth of cobalamin binding intestinal bacteria. Therefore, cobalamin concentrations should be measured every 3 to 6 months and subcutaneous therapy instituted where necessary. Some studies have suggested that patients with EPI may be zinc and/or copper deficient from depressed absorption. Therefore, the diet that is chosen should have adequate zinc and copper concentrations.
Recently, protein hydrolysate diets have become available for the management of adverse food reactions. These diets are highly digestible with “pre-digested” protein, and are of interest in the management of dogs with EPI. Biourge et al recently reported the use of a commercially available hydrolyzed soy isolate protein diet (consisting of 40% of calories from fat) in four male German Shepard Dogs with EPI and severe skin disease. The age of the dogs ranged from 2.5 years to 9.0 years. All four dogs had a previous diagnosis of EPI on the basis of history, clinical signs, indirect pancreatic function test (one dog) and serum canine TLI (three dogs). All dogs were lean (BSC 2/5), and, at the time of presentation, managed with high digestible diets, pancreatic enzyme supplementation and occasional antibiotic
therapy. Within 7 days of feeding the hydrolyzed soy protein isolate diet, all dogs had well formed feces, and no episode of diarrhea was observed over the 3 month follow-up. In addition, all 4 dogs gained weight (2-10kg), and were in optimal body condition after two months of dietary therapy. The results of this case series suggested that a high fat, highly digestible, soy-protein isolate hydrolysate diet is effective for the management of EPI in dogs. EPI requires life-time enzyme replacement therapy. Commercial enzyme replacers are available in powder, capsule and tablet format. Generally, enteric coated capsules and tablets appear to be less effective than enzyme powder. The enzyme should be mixed with the food prior to feeding. There have also been reports that suggest utilizing beef or pig pancreas. The only concern with this approach is the health risks associated with handling and feeding raw meats. Up to 83% of the lipase activity and 65% of the trypsin activity are lost in the acid pH of the stomach. Therefore the actual dose needed to control the clinical signs will need to be tailored to each patient. Some authors have suggested that controlling the acidity of the stomach using histamine-blocking agents may increase the effectiveness of the pancreatic enzyme supplementation This theory remains to be proven. With diet and enzyme replacer therapy, the diarrhea typically resolves in 3-7 days. The time to respond will also depend on concurrent small intestine bacterial overgrowth and mucosal dysfunction. Small intestinal overgrowth can be managed with antibiotic therapy such as metronizadole.
Wiberg et al studied the effect of long term enzyme replacement treatment in 76 German Shepherd Dogs or Rough Coated Collies with EPI. The gastrointestinal signs of EPI were controlled in approximately half of the dogs, and their general health was considered to be similar to normal dogs. Twenty percent of the dogs had a poor response to treatment, characterized by persistent high fecal volume, yellow feces and flatulence. Nonenteric-coated enzyme supplement, powdered enzyme, and raw chopped pancreas appeared to be equally effective in controlling clinical signs. Published in IVIS with the permission of the NAVC - ww.ivis.org
REFERENCES
1. Biourge VC, Fontaine J. Exocrine pancreatic
insufficiency (EPI) and adverse reaction to food: A
positive response to a high fat, soy isolate hydrolysate
based diet. Waltham International Science Symposium,
Bangkok, Thailand, October 28-31, 2003 p, 58
2. Hall EJ, Bond PM, McLean C, et al. A survey of the
diagnosis and treatment of canine exocrine pancreatic
insufficiency. J Small Anim Pract 1991;32:613-619.
3. Simpson KW, Morton DB, Batt RM. Effect of exocrine
pancreatic insufficiency on cobalamin absorption in dogs.
Am J Vet Res 1989;50:1233-1236.
4. Simpson KW, Batt RM, Jones D, et al. Effects of exocrine
pancreatic insufficiency and replacement therapy on the
bacterial flora of the duodenum in dogs. Am J Vet Res
1990;51:203-206
5. Simpson JW, Maskell IE, Quigg J, et al. The long-term
management of canine exocrine pancreatic insufficiency.
J Small Anim Pract 1994;35:133-138.
6. Suzuki A, Mizumoto A, Rerknimitr R, et al. Effect of
bacterial or porcine lipase with low- or high-fat diets on
nutrient absorption in pancreatic insufficient dogs.
Gastroenterology 1999;116: 431-437.
7. Westermarck E: Treatment of pancreatic degenerative
atrophy with raw pancreas homogenate and various
enzyme preparations. J Vet Med Assoc. 1987;34:728-
733.
8. Westermarck E, Junttila J, Wiberg M. The role of low
dietary fat in the treatment of dogs with exocrine
pancreatic insufficiency. Am J Vet Res 1995;56:600-605.
9. Wiberg ME, Lautala H-M, Westermarck E. Response to
long-term enzyme replacement treatment in dogs with
exocrine pancreatic insufficiency. J Am Vet Med Assoc
1998;1:86-90.
10. Wiberg ME, Westermarck E. Subclinical exocrine
pancreatic insufficiency in dogs. J Am Vet Med Assoc
2002;8.
11. Williams DA, Batt RM. Sensitivity and specificity of
radioimmunoassay of serum trypsin-like immunoreactivity
for the diagnosis of canine exocrine pancreatic
insufficiency. J Am Vet Med Assoc. 1988;192:195-200.
12. Williams DA, Batt RM, Mclean L. Bacterial overgrowth in
the duodenum of dogs with exocrine pancreatic
insufficiency.
___________________________________________________________________________________________________
The pancreas
Is a small light "pinkish tan" glandular organ positioned under the stomach and along side the duodenum (upper small intestine). The "endocrine" pancreas is the part of the pancreas that secretes hormones such as insulin and glucagon which regulate blood sugar. The "exocrine" pancreas produces enzymes used to digest food. These two different types of pancreatic tissues are all mixed together throughout the entire pancreas.
The pancreatic digestive enzymes include (1) proteases and trypsin to digest protein, (2) lipases to digest fats, and (3) amylase to digest starches. They are stored in inactive forms inside special granules in the exocrine pancreatic tissue (the “acinar cells” ) and are secreted into the duodenum (the first part of the small intestine after the stomach) when ground up food begins its passage out of the stomach. Once nutrients are broken down into smaller molecules (i.e. they are digested), they can be absorbed down the entire length of the GI tract. Without adequate production of these enzymes, food cannot be digested, nutrients cannot be absorbed and consequently the body and it's organs start to starve and everything becomes compromised. Without proper enzyme and dietery treatment, death happens, either by starvation or organ failure.
as adapted from http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html
Three major groups of enzymes are critical to efficient digestion are as follows:
1. Proteases
Digestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the pancreatic proteases. Several proteases are synthesized in the pancreas and secreted into the lumen of the small intestine. The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and packaged into special secretory granule vesicles as the inactive proenzymes trypsinogen and chymotrypsinogen.
Proteases are rather dangerous enzymes to have in cells, and packaging of an inactive precursor is a way for the cells to safely handle these enzymes. The secretory vesicles also contain a trypsin inhibitor which serves as an additional safeguard should some of the trypsinogen be activated to trypsin; following exocytosis this inhibitor is diluted out and becomes ineffective - the pin is out of the grenade.
Once trypsinogen and chymotrypsinogen are released into the lumen of the small intestine, they must be converted into their active forms in order to digest proteins. Trypsinogen is activated by the enzyme enterokinase, which is embedded in the intestinal mucosa.
Once trypsin is formed it activates chymotrypsinogen, as well as additional molecules of trypsinogen. The net result is a rather explosive appearance of active protease once the pancreatic secretions reach the small intestine.
Trypsin and chymotrypsin digest proteins into peptides and peptides into smaller peptides, but they cannot digest proteins and peptides to single amino acids. Some of the other proteases from the pancreas, for instance carboxypeptidase, have that ability, but the final digestion of peptides into amino acids is largely the effect of peptidases on the surface of small intestinal epithelial cells.
2. Pancreatic Lipase
A major component of dietary fat is triglyceride, or neutral lipid. A triglyceride molecule cannot be directly absorbed across the intestinal mucosa. it It must first be digested into a 2-monoglyceride and two free fatty acids. The enzyme that performs this hydrolysis is pancreatic lipase, which is delivered into the lumen of the gut as a constituent of pancreatic juice.
Sufficient quantities of bile salts must also be present in the lumen of the intestine in order for lipase to efficiently digest dietary triglyceride and for the resulting fatty acids and monoglyceride to be absorbed. This means that normal digestion and absorption of dietary fat is critically dependent on secretions from both the pancreas and liver.
3. Amylase
The major dietary carbohydrate for many species is starch, a storage form of glucose in plants. Amylase (technically alpha-amylase) is the enzyme that hydrolyses starch to maltose (a glucose-glucose disaccharide), as well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins. The major source of amylase in all species is pancreatic secretions, although amylase is also present in saliva of some animals, including humans.
In addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes, including ribonuclease, deoxyribonuclease, gelatinase and elastase.
Accurate diagnosis of Exocrine Pancreatic Insufficiency was the development of the Serum Trypsin-like Immunoreactivity test, a blood test. Prior to this, an assortment of inaccurate fecal tests were utilized. The TLI test looks for a normal level of trypsin-like enzymes in the bloodstream. In the normal animals, trypsin, an enzyme of protein digestion, is stored in the pancreas in an inactive form so as to avoid digestion of one’s own body. Still, trace amounts of active enzyme make it into the bloodstream. This is harmless, normal, and detectable. A dog or cat with EPI will have almost no Serum Trypsin-like Immunoreactivity in the bloodstream. The patient must be fasted for the test to be accurate but only a single blood sample is needed to make the diagnosis.
Dietary supplementation with digestive enzymes is an effective therapy for EPI even though most of the supplement given is digested in the stomach along with other dietary proteins. The little bit that survives the acid bath of the stomach and its own protein-digesting chemicals turns out to be enough to stop the diarrhea and enable the patient to actually gain some weight. Powdered enzymes (Viokase-V, Pancreazyme) seem to work the best though tablets are also available and some like to give raw chopped beef, porcine or lamb pancreas.
In the past, it was suggested that incubating the enzymes in the patient’s food would help initiate the digestion process in the food bowl, then this was stated as not true, then true and now not true. Unfortunately there has been a mis-understanding about the function of enzymes (even on this website!) with getting desired results but assumptions were made for the wrong reasons. Enzymes cannot incubate the food at room temperature, or if so very, very little actually incubates. The environment of the intestines and stomach are required for the enzymes to actually be activated. SO.... why has recently hands-on-experience with over 1,000+ positively confirmed EPI dogs of all breeds seem to have proven otherwise? Assumption. Since incubation of enzymes on food for a minimum of 20 minutes, longer (up to 1-2 hours) seems to work.....but what may be happening is that when softened food (vs. whole food) reaches the intestines and stomach it is then more easily broken down with the replacement enzymes. Hence, the mis-understanding. Mixing the enzymes well into the food prior to feeding the food appears to eliminate mouth sores and/or mouth bleeding that afflicts some dogs when given enzymes. Some vets recommend less enzymes and this also alleviates mouth sores and/or bleeding.
A highly digestibility diet is the best choice for an EPI patient. Although each EPI dog varies slightly from one another in their dietary requirement, the basic starting point with food, (if dry food) is to feed a grain-free kibble with no more than 4% fiber. There is new evidence that once on enzymes, most EPI dogs should be able to tolerate a normal amount of fat. As a matter of fact, restricted fat may be detrimental to the dog. HOWEVER, if there still is a digestive upset when fat is slowly added to the diet, there may be another gastrointestinal issue in addition to EPI where it then would be beneficial to limit the fat intake. If feeding raw meats, trim excess fat. Avoid grains, limit fruits and vegetables. Remember, managing EPI comes with a basic set of rules that are adjusted to suit each individual dog.
EPI patients commonly have an overgrowth of bacteria called SIBO, Small Intestinal Bacterial Overgrowth in their intestines which means that the unabsorbed nutrients in the tract have fed the bacteria living there (instead of the patient) and an overpopulation of bad bacteria has occurred. This results in a vitamin B-12 deficiency as the bacteria consume the vitamin (instead of the patient getting some). A course of 30 days of antibiotics (metronidazole or tylan) is advised to correct this problem especially early in the course of EPI treatment. Once antibiotics are given for 30 days, it is further advised to administer probiotics to allow "good" bacteria (good gut flora) to develop and not leave room for bad bacteria (SIBO) to take over again. A regimen of vitamin B12 injections are also recommended for patients with EPI if their B12 levels are affected, and many times they are so this should be checked.
Treatment is for life with enzyme supplementation. In the majority of dogs, a positive response to therapy is usually noticed within a week or two of beginning enzyme and dietary treatment. This does not mean they have achieved stabilization yet. Stabilization may take anywhere from weeks to months to a few years. Some dogs never re-gain all their weight back, others do. Responses can be excellent but approximately one dog in 5 will simply not respond well or at all. Many do not ever regain a normal amount of weight., others not only gain their original weight back but exceed it and have to be placed on diets.
After discussing the many, mind-boggling details of EPI which can be more than a little over-whelming, a wonderful group of EPI dog owners, Larry and friends (with a few modifications due to recent insight) constructed the following "EPI Quick Start Guide" for folks just just like you who want to learn in simple 1-2-3 format how to handle this horrible disease that their beloved companion may have.
There is no cure for EPI, but with proper care, your dog most likely can live a normal life. EPI has a genetic component
What is EPI? Your dog cannot produce the majority of digestive enzymes it needs. Untreated, your EPI dog will starve.
What to do?
1.ADD powdered (see exceptions, below) ENZYMES, e.g., Viokase, Pancrezyme,
2. STIR thoroughly. In many cases the food your dog was eating before can continue to be fed:. Exceptions: Food high in fiber (over 4%). Once on enzymes EPI dogs should be able to tolerate the much needed fat content HOWEVER if there is some other gastrointestinal situation going on (you may not even be aware of this) in addition to EPI you may have to restrict the fat content in their diet. Most EPI dogs do better if all grains are eliminated from their diet. (Rice, Oats, Wheat, etc)
3. WAIT for the food to soften (with the enzymes mixed in very well) for approximately 20-30 minutes to avoid possible mouth sores from the enzymes and for the food to soften for better ease of being digested with the enzymes in the intestinal track and stomach. . If you feed raw, cooked or canned, you may need a little less enzymes. If there’s a choice, try using a grain-free food.
In parts of the world where enzymes are not readily available as powder, coated tablets or capsules, e.g. Creon, may be used. These are fed just before or during the meal. Unless you are told to by your vet, the tablets or capsules should not be chewed. Vegetable-based enzymes, e.g. Enzyplex, are almost NEVER sufficient to treat EPI.
POOP. It’s all about the poop. Poop is the indicator for what is or is not working for your EPI dog. Even a slightly advanced case produces poop that’s loose, stinky
B12 Many EPI dogs will have difficulty absorbing B12, even with properly prepared meals. Maintaining B12 levels is one of the essential steps in continuing stability in the EPI dog. B12 supplementation is by way of injection. They are generally not expensive
SIBO. Is an associated condition called Small Intestinal Bacterial Overgrowth, when bad bacteria overwhelms the good bacteria, sometimes associated with high-grain-content dog foods. SIBO is generally treated with a vet prescribed, six-week course of antibiotics, normally Tylan (tylosin) or Flagyl (metronidazole). Your dog may or may not ever have SIBO, but it is a very common secondary condition with EPI.
As to your dog’s quality of life, they can (
Can you do this? YES! Follow these RULES: 1.Ritualize the process. 2.Be patient. 3.NEVER change more than one thing at a time. 4. Adjust, by TINY amounts, the enzymes up or down to fine tune. Allow at least five days between adjustments. 5.Keep a journal of changes. 6.During the early phases of stabilization NO treats, NO supplements, unless specifically instructed by your vet. When adding anything to an EPI dog’s diet, build up to the desired/required amounts.
------------------------------------------------------------------------------------------------------------------------------------
EPI in Cats
The following is from: http://www.ivis.org/advances/rcfeline/chap4part9/chapter.asp?LA=1
In: Encyclopedia of Feline Clinical Nutrition, Pibot P., Biourge V. and Elliott D.A. (Eds.). International Veterinary Information Service, Ithaca NY (www.ivis.org), Last updated: 28-Apr-2009; A5106.0409
Nutritional Management of Hepatobiliary and Pancreatic Diseases
C. Rutgers1 and V. Biourge2
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. 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.
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.
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.
References
- 1. Akol KG, Washabau RJ, Saunders HM, et al. Acute pancreatitis in cats with hepatic lipidosis. J Vet Intern Med 1993; 7: 205-209. - PubMed -
- 2. Bauer JE. Hepatic disease, nutritional therapy, and the metabolic environment. J Am Vet Med Assoc 1996; 209: 1850-1853.
- 3. Beatty JA, Barrs VR, Martin PA, et al. Spontaneous hepatic rupture in six cats with systemic amyloidosis. J Small Anim Pract 2002; 43: 355-363. - PubMed -
- 4. Biourge V. Clinical nutrition in liver disease, in Proceedings. 14th Annu ECVIM-CA Congress 2004; 63-65.
- 5. Biourge V. Nutrition and liver disease. Semin Vet Med Surg 1997; 12: 34-44. - PubMed -
- 6. Biourge V, Groff JM, Fisher C, et al. Nitrogen balance, plasma free amino acid concentrations and urinary orotic acid excretion during long-term fasting in cats. J Nutr 1994a; 124: 1094-1103. - PubMed -
- 7. Biourge VC, Groff JM, Munn RJ, et al. Experimental induction of hepatic lipidosis in cats. Am J Vet Res 1994b; 55: 1291-1302. - PubMed -
- 8. Biourge VC, Massat B, Groff JM, et al. Effect of protein, lipid, or carbohydrate supplementation on hepatic lipid accumulation during rapid weight loss in obese cats. Am J Vet Res 1994c; 55: 1406-1415. - PubMed -
- 9. Biourge VC, Fontaine J. Exocrine pancreatic insufficiency and adverse reaction to food in dogs: a positive response to a high-fat, soy isolate hydrolysate-based diet. J Nutr 2004, 134: 2166s-2168s.
- 10. Blanchard G, Paragon BM, Milliat F, et al. Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis. J Nutr 2002; 132: 204-210. - PubMed -
- 11. Caney SMA, Gruffydd-Jones TJ. Feline inflammatory liver disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat. 6th edition. Philadelphia: WB Saunders Co, 2005; 1448-1453.
- 12. Center SA. Chronic hepatitis, cirrhosis, breed-specific hepatopathies, copper storage hepatopathy, suppurative hepatitis, granulomatous hepatitis, and idiopathic hepatic fibrosis. In: Strombeck's Small Animal Gastroenterology. 3rd ed. Philadelphia: WB Saunders Co, 1996: 705. - Available from amazon.com -
- 13. Center SA. Feline hepatic lipidosis. Vet Clin Small Anim 2005; 35: 225-269. - PubMed -
- 14. Center SA. Nutritional support of dogs and cats with hepatobiliary disease. J Nutr 1998; 128: 2733S-2746S. - PubMed -
- 15. Center SA. Pathophysiology of liver disease: Normal and abnormal function. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat. 5th edition. Philadelphia: WB Saunders Co, 2000a; 533-632. - Available from amazon.com -
- 16. Center SA, Elston TH, Rowland PH, et al. Fulminant hepatic failure associated with oral administration of diazepam in 11 cats. J Am Vet Med Assoc 1996; 209: 618-625. - PubMed -
- 17. Center SA, Randolph JF, Warner KL, et al. The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats. J Vet Intern Med 2005; 19: 303-314. - PubMed -
- 18. Center SA, Warner K, Corbett J, et al. Proteins invoked by vitamin K absence and clotting times in clinically ill cats. J Vet Int Med 2000b; 14: 292-297. - PubMed -
- 19. Center SA, Warner KL, Erb HN. Liver glutathione concentrations in dogs and cats with naturally occurring liver disease. Am J Vet Res 2002; 63: 1187-1197. - PubMed -
- 20. d'Anjou MA, Penninck D, Cornejo L, et al. Ultrasonographic diagnosis of portosystemic shunting in dogs and cats. Vet Radiol Ultrasound 2004; 45: 424-437. - PubMed -
- 21. Day MJ. Immunohistochemical characterization of the lesions of feline progressive lymphocytic cholangitis/cholangiohepatitis. J Comp Pathol 1998; 119: 135-147. - PubMed -
- 22. De Cock HEV, Forman MA, Farver TB, et al. Prevalence and histopathologic characteristics of pancreatitis in cats. Vet Pathol 2007; 44: 39-49. - PubMed -
- 23. Delaney SJ. Management of anorexia in dogs and cats. Vet Clin North Am Small Anim Pract 2006; 36: 1243-1249. - PubMed -
- 24. Feher J, Lengyel G, Blazovics A. Oxidative stress in the liver and biliary tract diseases. Scand J Gastroenterol Suppl 1998; 38-46. - PubMed -
- 25. Ferreri JA, Hardam E, Kimmel SE, et al. Clinical differentiation of acute necrotizing from chronic nonsuppurative pancreatitis in cats: 63 cases (1996-2001). J Am Vet Med Assoc 2003; 223: 469-474. - PubMed -
- 26. Forman MA, Marks SL, De Cock HE, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med 2004; 18: 807-815. - PubMed -
- 27. Fyfe JC. Feline intrinsic factor (IF) is pancreatic in origin and mediates ileal cobalamin (CBL) absorption. J Vet Intern Med 1993; 7: 133.
- 28. Fuentealba IC, Aburto EM. Animal models of copper-associated liver disease. Comp Hepatol 2003; 2: 5 - PubMed -
- 29. Gagne JM, Armstrong PJ, Weiss DJ, et al. Clinical features of inflammatory liver disease in cats: 41 cases (1983-1993). J Am Vet Med Assoc 1999; 214: 513-516. - PubMed -
- 30. Gerhardt A, Steiner JM, Williams DA, et al. Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats. J Vet Intern Med 2001; 15: 329-333. - PubMed -
- 31. Gupta R, Patel K, Calder PC, et al. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis. Pancreatology 2003; 3: 406-413. - PubMed -
- 32. Haney DR, Christiansen JS, Toll JD. Severe cholestatic liver disease secondary to liver fluke (Platynosomum concinnum) infection in three cats. J Am Anim Hosp Assoc 2006; 42: 234-237. - PubMed -
- 33. Harkin KR, Cowan LA, Andrews GA, et al. Hepatotoxicity of stanozolol in cats. J Am Vet Med Assoc 2000; 217: 681-684. - PubMed -
- 34. Haynes JS, Wade PR. Hepatopathy associated with excessive hepatic copper in a Siamese cat. Vet Pathol 1995; 32: 427 – 429. - PubMed -
- 35. Hecht S, Penninck DG, Keating JH. Imaging findings in pancreatic neoplasia and nodular hyperplasia in 19 cats. Vet Radiol Ultrasound 2007; 48: 45-50. - PubMed -
- 36. Hill RC, Van Winkle TJ. Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat. A retrospective study of 40 cases (1976-1989). J Vet Int Med 1993; 7: 25-33. - PubMed -
- 37. Holt DE, Schelling CG, Saunders HM, et al. Correlation of ultrasonographic findings with surgical, portographic, and necropsy findings in dogs and cats with portosystemic shunts: 63 cases (1987-1993). J Am Vet Med Assoc 1995; 207: 1190-1193. - PubMed -
- 38. Hooser SB. Hepatotoxins. In: Bonagura JD (ed). Kirk’s Current Veterinary Therapy XIII. Philadelphia: WB Saunders Co, 2000; 217-219. - Available from amazon.com -
- 39. Hunt GB, Kummeling A, Tisdall PL, et al. Outcomes of cellophane banding for congenital portosystemic shunts in 106 dogs and 5 cats. Vet Surg 2004; 33: 25-31. - PubMed -
- 40. Ibrahim WH, Bailey N, Sunvold GD, et al. Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss. Am J Vet Res 2003; 64: 1265-1277. - PubMed -
- 41. Jergens AE, Morrison JA, Miles KG, et al. Percutaneous endoscopic gastrojejunostomy tube placement in healthy dogs and cats. J Vet Intern Med 2007; 21: 18-24. - PubMed -
- 42. Johnson CD. Antioxidants in acute pancreatitis. Gut 2007; 56: 1344-1345.
- 43. Johnston K, Lamport A, Batt RM. An unexpected bacterial flora in the proximal small intestine of normal cats. Vet Rec 1993; 132: 362-363.
- 44. Johnston KL, Swift NC, Forster-van Hijfte M, et al. Comparison of the bacterial flora of the duodenum in healthy cats and cats with signs of gastrointestinal tract disease. J Am Vet Med Assoc. 2001 Jan 1; 218:48-51. - PubMed -
- 45. Kim SW, Rogers QR, Morris JG. Maillard reactions products in purified diets induce taurine depletion in cats which is reversed by antibiotics. J Nutr 1996; 126: 195-201. - PubMed -
- 46. Kimmel SA, Washabau RJ, Drobatz KJ. Incidence and prognostic value of low plasma ionized calcium concentration in cats with acute pancreatitis: 46 cases (1996-1998). J Am Vet Med Assoc 2001; 219: 1105-1109. - PubMed -
- 47. Krahenbuhl S, Reichen J. Carnitine metabolism in patients with chronic liver disease. Hepatology 1997; 25: 148-153. - PubMed -
- 48. Kyles AE, Hardie EM, Mehl M, et al. Evaluation of ameroid ring constrictors for the management of single extrahepatic portosystemic shunts in cats: 23 cases (1996 – 2001). J Am Vet Med Assoc 2002; 220: 1341 – 1347. - PubMed -
- 49. Laflamme DP. Nutritional management of liver disease. In: Kirk’s Current Veterinary Therapy XIII, Bonagura JW (ed). WB Saunders Co, Philadephia, 2000: 277-293.
- 50. Langdon P, Cohn LA, Kreeger JM, et al. Acquired portosystemic shunting in two cats. J Am Anim Hosp Assoc 2002; 38: 21-27. - PubMed -
- 51. Lasztity N, Hamvas J, Biro L, et al. Effect of enterally administered n-3 polyunsaturated fatty acids in acute pancreatitis - a prospective randomized clinical trial. Clin Nutr 2005; 24: 198-205. - PubMed -
- 52. Leveille R, Biller DS, Shiroma JT. Sonographic evaluation of the common bile duct in cats. J Vet Int Med 1996; 10: 296-299. - PubMed -
- 53. Levy JK, Bunch SE, Komtebedde J. Feline portosystemic vascular shunts. In: Bonagura J, ed. Kirk’s Current Veterinary Therapy Small Animal Practice XII. Philadelphia: WB Saunders Co, 1995; 743-749. - Available from amazon.com -
- 54. Lisciandro SC, Hohenhaus A, Brooks M. Coagulation abnormalities in 22 cats with naturally occurring liver disease. J Am Vet Med Assoc 1998; 12: 71-75. - PubMed -
- 55. Lucke VM, Davies JD. Progressive lymphocytic cholangitis in the cat. J Small Anim Pract 1984; 25: 247.
- 56. Maddison JE. Newest insights into hepatic encephalopathy. Eur J Comp Gastroent 2000; 5: 17-21.
- 57. Makola D, Krenitsky J, Parrish CR. Enteral feeding in acute and chronic pancreatitis. Gastrointest Endosc Clin N Am 2007; 17: 747-764. - PubMed -
- 58. Mansfield CS, Jones BR. Review of feline pancreatitis, part one: the normal feline pancreas, the pathophysiology, classification, prevalence and aetiologies of pancreatitis. J Feline Med Surg 2001a; 3: 117-124. - PubMed -
- 59. Mansfield CS, Jones BR. Review of feline pancreatitis, part two: clinical signs, diagnosis and treatment. J Feline Med Surg 2001b; 3: 125-132. - PubMed -
- 60. Marchesini G, Fabbri A, Bianchi G, et al. Zinc-supplementation and amino-acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 1996; 23: 1084-1092. - PubMed -
- 61. Marks SL, Rogers QR, Strombeck DR. Nutritional support in hepatic disease. Part I. Metabolic alterations and nutritional considerations in dogs and cats. Comp Cont Educ Pract Vet (Small Anim) 1994; 971-978.
- 62. Marik PE, Zatoga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ 2004; 328: 1407. - PubMed -
- 63. Meertens NM, Bokhove CA, van den Ingh TS. Copper-associated chronic hepatitis and cirrhosis in a European Shorthair cat. Vet Pathol 2005; 42: 97-100. - PubMed -
- 64. Michel KE. Nutritional management of liver disease. Vet Clin North Am Small Anim Pract 1995; 25: 485-501. - PubMed -
- 65. Newell SM, Selcer BA, Girard E, et al. Correlations between ultrasonographic findings and specific hepatic diseases in cats: 72 cases (1985- 1997). J Am Vet Med Assoc 1998; 213: 94-98. - PubMed -
- 66. Nicholson BT, Center SA, Randolph JF, et al. Effects of oral ursodesoxycholic acid in healthy cats on clinicopathological parameters, serum bile acids and light microscopic and ultrastructural features of the liver. Res Vet Sci 1996; 61: 258-262. - PubMed -
- 67. Perry LA, Williams DA, Pidgeon G, et al. Exocrine pancreatic insufficiency with associated coagulopathy in a cat. J Am Anim Hosp Assoc 1991; 27: 109-114.
- 68. Remillard RL, Saker KE. Nutritional management of hepatic conditions. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat. 6th edition. Philadelphia: WB Saunders Co, 2005; 574-577.
- 69. Ruaux CG, Steiner JM, Williams DA. Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J Vet Intern Med 2005; 19: 155–160. - PubMed -
- 70. Scherk M, Center SA. Toxic, metabolic, infectious, and neoplastic liver diseases. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat. 6th edition. Philadelphia: WB Saunders Co, 2005; 1464-1477.
- 71. Schunk CM. Feline portosystemic shunts. Semin Vet Med Surg (Small Anim) 1997; 12: 45-50. - PubMed -
- 72. Seaman RL. Exocrine pancreatic neoplasia in the cat: a case series. J Am Anim Hosp Assoc 2004; 40: 238-245. - PubMed -
- 73. Simpson KW. Feline pancreatitis. Waltham Focus 2005; 15:13-19.
- 74. Simpson KW, Fyfe J, Cornetta A, et al. Subnormal concentrations of serum cobalamin (Vitamin B12) in cats with gastrointestinal disease. J Vet Int Med 2001; 15: 26-32. - PubMed -
- 75. Sokol RJ, Twedt DJ, McKim J, et al. Oxidant injury to hepatic mitochondria in patients with Wilson’s disease and Bedlington terriers with copper toxicosis. Gastroenterology 1994; 107: 1788-1798. - PubMed -
- 76. Sokol RJ. Fat-soluble vitamins and their importance in patients with cholestatic liver disease. Pediatr Gastroenterol 1994; 23: 673-705. - PubMed -
- 77. Steiner JM. Diagnosis of pancreatitis. Vet Clin North Am Small Anim Pract 2003; 33: 1181-1195. - PubMed -
- 78. Steiner JM, Williams DA. Feline exocrine pancreatic disorders. Vet Clin North Am Sm Anim Pract 1999; 29: 551-574. - PubMed -
- 79. Steiner JM, Williams DA. Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency. J Vet Intern Med 2000; 14: 627-629. - PubMed -
- 80. Steiner JM, Williams DA. Feline exocrine pancreatic disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat. 6th edition. Philadelphia: WB Saunders Co, 2005; 1489-1495.
- 81. Steiner JM, Wilson BG, Williams DA. Development and analytical validation of a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity in serum. Can J Vet Res 2004; 68: 309-314. - PubMed -
- 82. Suzuki A, Mizumoto A, Rerknimitz R, et al. Effect of bacterial or porcine lipase with low fat or high fat diets on nutrient absorption in pancreatic-insufficient dogs. Gastroenterology 1999; 116: 431-437. - PubMed -
- 83. Swift NC, Marks SL, MacLachlan J, et al. Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats. J Am Vet Med Assoc 2000; 217: 37-42. - PubMed -
- 84. Tillson DM, Winkler JT. Diagnosis and treatment of portosystemic shunts in the cat. Vet Clin North Am Small Anim Pract 2002; 32: 881-899. - PubMed -
- 85. Trainor D, Center SA, Randolph F, et al. Urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in cats. J Vet Intern Med 2003; 17: 145-153. - PubMed -
- 86. Van der Linde-Sipman JS, Niewold TA, Tooten PCJ, et al. Generalized AA-amyloidosis in Siamese and Oriental cats. Vet Immunol Immunopath 1997; 56: 1-10. - PubMed -
- 87. Wang KY, Panciera DL, Al-Rukibat RK, et al. Accuracy of ultrasound-guided fine-needle aspiration of the liver and cytologic findings in dogs and cats: 97 cases (1990 – 2000). J Am Vet Med Assoc 2004; 224: 75-78. - PubMed -
- 88. Webster CRL. New insights into the cytoprotective action of ursodeoxycholate. In: Proceedings of the ACVIM Forum 2006; 639-641.
- 89. Weiss DJ, Gagne J, Armstrong PJ. Inflammatory liver diseases in cats. Comp Cont Educ 2001; 23: 364-373.
- 90. Weiss DJ, Gagne JM, Armstrong PJ. Relationship between inflammatory hepatic disease and inflammatory bowel disease, pancreatitis, and nephritis in cats. J Am Vet Med Assoc 1996; 209: 1114-1116. - PubMed -
- 91. Whittemore JC, Campbell VL. Canine and feline pancreatitis. Comp Cont Educ Pract Vet (Small Anim) 2005; 766-776.
- 92. Williams DA. Diseases of the exocrine pancreas. BSAVA Manual of canine and feline gastroenterology. 2nd edition, 2005: 222-239.
- 93. WSAVA Liver Standardization Group. Morphological classification of biliary disorders of the canine and feline liver. In: Rothuizen J, Bunch SE, Charles JA, eds. WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Disease. Philadelphia: WB Saunders Co, 2006. - Available from amazon.com -
- 94. Zoran DL. The carnivore connection to nutrition in cats. J Am Vet Med Assoc 2002; 221: 1559–1567.
- 95. Zoran DL. Pancreatitis in cats: diagnosis and management of a challenging disease. J Am Anim Hosp Assoc 2006; 42: 1-9. - PubMed -
- 96. Schulz HU, Niederau C, Klonowski-Stumpe H, et al. Oxidative stress in acute pancreatitis. Hepatogastroenterology 1999; 46: 2736-2750. - PubMed -