Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.     

Effect of exocrine pancreatic insufficiency on cobalamin absorption in dogs

The possibility that the canine pancreas might have an important role in the physiologic absorption of cobalamin (vitamin B12) has been explored by determining the effect of exocrine pancreatic insufficiency on cobalamin absorption and by examining the subsequent influence of bovine pancreatic enzymes and canine pancreatic juice. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and confirmed by indirect assessment of exocrine pancreatic function. Cobalamin absorption was determined by oral administration of cyano[58Co]cobalamin and quantitation of radioactivity in blood, urine, and feces during 48 hours. Pancreatic duct ligation resulted in a significant (P less than 0.001) decrease in cobalamin absorption, which was not restored by oral administration of bovine pancreatic enzymes, despite considerable improvements in steatorrhea and in vivo proteolytic activities. In marked contrast, malabsorption of cobalamin was significantly (P less than 0.05) reversed by oral administration of canine pancreatic juice. These results indicate that pancreatic secretions have an important role in the normal absorption of cobalamin in the dog, a role that does not appear to be attributable to pancreatic enzymes, but is consistent with the existence of a pancreatic intrinsic factor in this species.     

Bacterial overgrowth in the duodenum of dogs with exocrine pancreatic insufficiency

Bacterial overgrowth (greater than 10(5) colony-forming units/ml duodenal juice) in the duodenum was demonstrated in 8 of 11 dogs with exocrine pancreatic insufficiency (EPI). In 4 of these 8 dogs, the overgrowth included large numbers (greater than 10(4) colony-forming units/ml) of obligate anaerobic bacteria and was associated with decreased activities of several brush border marker enzymes and, in 2 dogs, with partial villous atrophy in the jejunum. Changes in the jejunal mucosa of the remaining dogs (with either no overgrowth or overgrowth of aerobic bacteria alone) were characterized by increased activities of some brush border disaccharides and of lysosomal hydrolases. One dog was euthanatized without treatment, at the owner's request. The response of 4 of the remaining 10 dogs treated with enzyme replacement alone was poor or suboptimal, and all of these 4 dogs had bacterial overgrowth. One of these dogs had an excellent clinical response when also given oxytetracycline orally for 14 days, but the other 3 dogs did not improve further in response to the same treatment. It was concluded that bacterial overgrowth in the duodenum is common in dogs with EPI and that, when such overgrowth includes large numbers of obligate anaerobes, there may be associated biochemical and morphologic abnormalities in jejunal mucosa. Functional disturbances related to abnormal intestinal microflora may be responsible for the failure of some dogs with EPI to respond fully to oral pancreatic enzyme supplementation without antibiotic therapy.     

Use of pulmonary hydrogen gas excretion to detect carbohydrate malabsorption in dogs

Pulmonary H2 excretion was measured in 10 healthy dogs, in 6 dogs with pancreatic exocrine insufficiency, and in 6 dogs with chronic small intestinal disease. Concentration of expired H2 in fasted healthy dogs was 0.9 +/- 0.1 ppm (mean +/- SEM) and peak H2 concentration of 1.4 +/- 0.2 ppm was detected up to 8 hours after feeding. Dogs with pancreatic exocrine insufficiency had fasting expired H2 concentrations of 3.3 +/- 0.9 ppm, which increased to a mean peak H2 concentration of 28.8 +/- 2.0 ppm 6.5 hours after feeding. Following xylose administration, expired H2 concentrations increased from fasting concentrations of 3.6 +/- 0.9 ppm to peak at 19.0 +/- 2.0 ppm in 1.5 hours. Blood xylose concentrations were diagnostic for carbohydrate malabsorption in 4 of 6 dogs with pancreatic exocrine insufficiency. Plasma p-aminobenzoic acid concentration identified bentiromide maldigestion in all dogs with pancreatic exocrine insufficiency. In 3 pancreatic exocrine insufficient dogs tested, pancreatic enzyme replacement therapy partially corrected carbohydrate malabsorption. Fasting expired H2 concentration was 5.3 +/- 1.3 ppm in dogs with chronic small intestinal disease and increased to a peak H2 of 72.2 +/- 18.0 ppm 7 hours after feeding. Following administration of xylose to dogs with chronic small intestinal disease, fasting expired H2 concentration increased from 3.0 +/- 1.0 ppm to a peak of 35.5 +/- 7.2 ppm at 2 hours. Blood xylose concentration was abnormal in only 2 of 6 dogs with chronic small intestinal disease. Results of these studies indicate that expired H2 analysis can identify carbohydrate malabsorption in dogs with pancreatic exocrine insufficiency or chronic small intestinal disease, and that pulmonary H2 testing is more sensitive than xylose absorption testing for the identification of carbohydrate malabsorption.     

Studies on nutrient digestibilities (pre-caecal and total) in pancreatic duct-ligated pigs and the effects of enzyme substitution

Introduction Exocrine pancreatic insufficiency causes digestive disturbances in humans and animals. However, although clinical symptoms of pancreatic insufficiency, e.g. steatorrhoea, only occurs after loss of 80–90% normal pancreatic secretory capacity (D i M agno et al. 1973), pancreatic enzyme supplementation does not always result in normalization of digestion (especially of fat), even with high doses of enzymes (L& ouml ; ser and F& ouml ; lsch 1995). In order to better understand the physiological and the pathological consequences of exocrine pancreatic insufficiency in humans as well as its therapy with enzyme substitution, studies have been made using an animal model of induced pancreatic exocrine insufficiency. Hither to, studies concerning pancreatic duct ligation and/or the influence of enzyme substitution have mainly been focused on estimation of enzyme activities in chyme (e.g. A bello et al. 1989) and/or on faecal analyses of total digestibility (e.g. I mmondi et al. 1972). To get more information on effects of enzymes (natural or substituted) it seems necessary to investigate the site and extent of digestion more intensively (S udendey 1995). Therefore a pig model of induced pancreatic exocrine insufficiency, via pancreatic duct ligation, was chosen and pre-caecal digestibility was measured by means of an ileo-caecal re-entrant fistula. Studies on the digestibility of a high fat diet were made, since cystic fibrosis patients with exocrine pancreatic insufficiency are recommended to take in high amounts of energy to avoid catabolic metabolism and nowadays these high energy diets comprise increasing proportions of fat (D urie and P encharz 1989; S hepherd et al. 1991). The following aspects were investigated in controls and pancreatic duct-ligated pigs that were fed a high fat diet: changes in the composition of ileal chyme and faeces; effects on nutrient digestibility (pre-caecal and total); efficacy of enzyme substitution in total exocrine pancreatic insufficiency.     

Diagnosis and management of malabsorption in dogs

Malabsorption can result from interference with either the degradation or absorption phases in the handling of dietary constituents and represents an important cause of weight loss and diarrhoea in dogs. Effective treatment depends on identification and understanding of the underlying disease which could affect the functional capacity of the exocrine pancreas or small intestine. Exocrine pancreatic insufficiency (EPI) can be identified by a low concentration of trypsin-like immunoreactivity in serum and results in serious malabsorption due to interference with degradation of carbohydrate, protein and fat. Treatment with oral pancreatic extract complemented by a low fat, high quality protein diet, is effective in many cases. Refractory cases may need additional treatment with an oral antibiotic for small intestinal bacterial overgrowth (SIBO), and H₂-receptor blockers to help prevent denaturation of the pancreatic extract by stomach acid. The pancreas plays a key role in the normal absorption of cobalamin (vitamin B₁₂) in dogs and malabsorption of cobalamin in EPI may not resolve with treatment so that cobalamin may need to be given parenterally. Small intestinal disease may result in interference with the number or functioning of individual enterocytes, in some cases accompanied by cellular infiltration of the mucosa. Diagnosis depends on indirect assessment of intestinal damage, for example by assay of serum vitamins and determination of intestinal absorption and permeability, and in selected cases followed by endoscopic examination, intestinal biopsy and culture of duodenal juice. Treatment depends on the disease and may include oral antibiotic for SIBO and immunosuppressive drugs for infiltrative disease. Dietary management is also important, for example with a restricted fat diet containing highly digestible carbohydrate and high quality protein, and when a dietary sensitivity is suspected a restriction diet of a selected protein source may be needed.     

Laboratory tests for diagnosis of gastrointestinal and pancreatic diseases

The panel of laboratory tests available for diagnosis of gastrointestinal (GI) diseases in dogs and cats is wide, and, recently, several new tests have been developed. This article will focus on advances in laboratory tests that are available for the general practitioner for diagnosis of GI diseases. Laboratory tests for diagnosis of gastric and intestinal infectious diseases include fecal parasite screening tests, enzyme-linked immunosorbent assays for parvoviral enteritis, and some specific bacterial tests like fluorescent in situ hybridization for identification of specific bacteria attached to the intestinal epithelial cells. Serum concentrations of folate and cobalamin are markers of intestinal absorption, but are also changed in exocrine pancreatic insufficiency and intestinal bacterial overgrowth. Hypocobalaminemia is common in GI and pancreatic disease. Decreased serum trypsin-like immunoreactivity is a very sensitive and specific test for the diagnosis of exocrine pancreatic insufficiency in dogs and cats. Serum pancreatic lipase is currently the most sensitive and specific test to identify pancreatic cell damage and acute pancreatitis. However, serum canine pancreas-specific lipase is less sensitive in canine chronic pancreatitis. Increased serum trypsin-like immunoreactivity is also specific for pancreatic damage but is less sensitive. It is very likely that further studies will help to better specify the role of these new tests in the diagnosis of canine and feline pancreatic diseases.     

Tylosin-responsive chronic diarrhea in dogs

Fourteen dogs had shown chronic or intermittent diarrhea for more than 1 year. Diarrhea had been successfully treated with tylosin for at least 6 months but recurred when treatment was withdrawn on at least 2 occasions. Tylosin-responsive diarrhea (TRD) affects typically middle-aged, large-breed dogs and clinical signs indicate that TRD affects both the small and large intestine. Treatment with tylosin eliminated diarrhea in all dogs within 3 days and in most dogs within 24 hours. Tylosin administration controlled diarrhea in all dogs, but after it was discontinued, diarrhea reappeared in 12 (85.7%) of 14 dogs within 30 days. Prednisone given for 3 days did not completely resolve diarrhea. Probiotic Lactobacillus rhamnosus GG did not prevent the relapse of diarrhea in any of 9 dogs so treated. The etiology of TRD, a likely form of antibiotic-responsive diarrhea (ARD) is unclear. The following reasons for chronic diarrhea were excluded or found to be unlikely: parasites, exocrine pancreatic insufficiency, inflammatory bowel disease, small intestinal bacterial overgrowth, enteropathogenic bacteria (Salmonella spp., Campylobacter spp., Yersinia spp., or Lawsoni intracellularis), and Clostridium perfringens enterotoxin and Clostridium difficile A toxin. A possible etiologic factor is a specific enteropathogenic organism that is a common resident in the canine gastrointestinal tract and is sensitive to tylosin but difficult to eradicate. Additional studies are required to identify the specific cause of TRD.     

Feline exocrine pancreatic disorders.

Despite the uncommon clinical diagnosis, cats frequently suffer from disorders of the exocrine pancreas. Pancreatitis is the most common feline exocrine pancreatic disorder. Pancreatitis can be acute or chronic and mild or severe. The etiology of most cases of feline pancreatitis is idiopathic. Some cases have been associated with severe abdominal trauma, infectious diseases, cholangiohepatitis, and organophosphate and other drug intoxication. The clinical presentation of cats with pancreatitis is nonspecific. Vomiting and signs of abdominal pain, which are the clinical signs most commonly observed in humans and dogs with pancreatitis, are only uncommonly observed in cats with pancreatitis. Routine laboratory findings are also nonspecific. Abdominal ultrasonography is a valuable diagnostic tool in feline patients with pancreatitis. Serum activities of lipase and amylase are rarely increased in cats with pancreatitis; however, these cats often have elevated serum fTLI concentrations. The goals of management are removal of the inciting cause, provision of supportive and symptomatic therapy, and careful monitoring for and aggressive treatment of systemic complications. Exocrine pancreatic insufficiency is a syndrome caused by insufficient synthesis of pancreatic digestive enzymes by the exocrine portion of the pancrease. The clinical signs most commonly reported are weight loss, loose and voluminous stools, and greasy soiling of the hair coat. Serum fTLI is subnormal in affected cats. Treatment of cats with EPI consists of enzyme supplementation with powdered pancreatic extracts or raw beef pancreas. Many cats with EPI have concurrent small intestinal disease. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require parenteral cobalamin supplementation. Pancreatic adenocarcinoma is the most common neoplastic condition of the exocrine pancreas in the cat. At the time of diagnosis, the tumor has already metastasized in most cases, and the prognosis is poor. Pancreatic pseudocyst, pancreatic abscess, pancreatic parasites, pancreatic bladder, and nodular hyperplasia are other exocrine pancreatic disorders, that are less commonly seen in cats.     

Determination of fecal fat and trypsin output in the evaluation of chronic canine diarrhea.

Quantitative fat and trypsin analysis was done on the feces of dogs with chronic diarrhea. The results of clinical examination, quantitative fecal analysis, and other laboratory tests permitted assignment of the dogs into one of 4 groups: (1)pancreatic exocrine insufficiency,(2)small intestinal malabsorption,(3)colitis, and(4)other nonspecific or incompletely diagnosed diarrhea. The mean 24-hour fat output was significantly higher (p less than 0.01) in dogs with malabsorption or pancreatic insufficiency than in clinically normal dogs, dogs with colitis, or dogs with nonsteatorrheic diarrheas. The mean 24-hour trypsin output with pancreatic insufficiency was significantly (P less than 0.01) lower, and in dogs with malabsorption, significantly (P less than 0.05) higher than in clinically normal dogs. Normalization of the output data for body weight enhanced the value of fat and trypsin analyses in the differentiation of pancreatic insufficiency and intestinal malabsorption from other causes of chronic canine diarrhea.     

Intestinal microflora: elimination of germfree characteristics by components of the normal microbial flora.

Strict anaerobic bacteria are the predominant constituents of the intestinal flora of animals and man, the commonly studied aerobic bacteria comprise only a small percentage of the total intestinal flora. Dominating anaerobes include eubacteria, Bacteroides, fusiformis, peptostreptococci, propionibacteria. The intestinal mucosal epithelia is covered with a mucous layer which is extremely rich in anaerobes. Various germfree anomalies may be selectively redressed by various species of the intestinal flora. Obligate and moderate anaerobes are the active strains in elimination of germfree characteristics, in reduction of enlarged cecum in germfree rodents. The metabolic activity of the intestinal bacteria has been discussed.     

Exocrine Pancreatic Insufficiency in the Cat

Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient amount of pancreatic digestive enzymes in the small intestine. Clinical signs most commonly reported in cats with EPI are weight loss, loose and voluminous stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair coat in the perianal region. Serum feline trypsin-like immunoreactivity concentration is the diagnostic test of choice for the diagnosis of affected cats. Treatment of cats with EPI consists of enzyme supplementation with either a powdered pancreatic extract or raw pancreas. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require lifelong parenteral cobalamin supplementation. Most cats respond well to therapy and can have a normal life expectancy and quality of life.     

Comparison of the bacterial and fungal flora in the pharynx of normal horses and horses affected with pharyngitis

A total of 43 horses were used for the study of the pharyngeal bacterial flora. The median value of the number of bacteria in the group of 19 normal horses was 3.8 × 10⁴ cfu/g of secretions. This value was 6.4 × 10⁴cfu/g in horses with grade I pharyngitis, 1.3 × 10⁵ cfu/g in horses with grade II pharyngitis and 3.5 × 10⁶ cfu/g in horses affected with grades III and IV pharyngitis. Corynebacterium spp, coagulase-negative staphylococci, Nocardia spp, Moraxella spp and Enterobacter spp were the most frequently encountered bacteria in the normal animals as well as in horses affected with pharyngitis of grades I or II. Moraxella spp were isolated in 87.5% of the horses with pharyngitis of grades III and IV, followed by Streptococcus zooepidemicus, Pseudomonas aeruginosa, coagulase-negative staphylococci and Enterobacter spp. No fastidious bacteria, nor strict anaerobes were isolated from any of the 43 horses. None of the microorganisms were found in 100% of the animals and the majority of the isolates were opportunistic bacteria. These results demonstrate that the isolation of Moraxella spp and S. zooepidemicus in large numbers is frequent in horses with lymphoid follicular hyperplasia grades III and IV. Fungi were isolated in small numbers from two or three horses in each group.     

Influence of glucagon on exocrine pancreatic function as determined by the Lundh test in dogs

Exocrine pancreatic function was investigated by means of the Lundh test model in dogs with chronic duodenal and gastric fistulas. The test was standardized and the effect of glucagon on exocrine pancreatic secretion was evaluated. The mean tryptic activity detected in 18 tests in 6 dogs was 32.25 +/- 5.25 muEqH+/minute/ml, which is considerably higher than that observed in man. The administration of glucagon was followed by a significant decrease (30.8%) in the volume of the duodenal contents and a more pronounced depression of the enzyme concentrations (trypsin 59%, chymotrypsin 53.3%). It is concluded that the Lundh test affords a valuable experimental model for the investigation of exocrine pancreatic function in dogs.     

Evaluation of the anaerobic method for the analysis of fecal microflora of beagle dogs.

The plate-in-bottle method of Mitsuoka et al. (1969) for the counting of fecal bacteria in beagle dogs was superior to an anaerobic jar method. Comparisons of three nonselective media, such as medium 10 supplemented with 10% cecal extract of dogs (designated as M10C), M10 with 10% fecal extract of dogs (M10F), and M10, by the plate-in-bottle method indicated that the visible bacterial counts for M10C were higher than those for M10 and M10F. The high percentage (18.4%) of numbers of the extremely oxygen-sensitive anaerobes to the fecal total counts by using the plate-in-bottle method with M10C was also observed.     

Enteric bacteria: Friend or foe?

The normal gastrointestinal tract contains an enormous number of aerobic and anaerobic bacteria which normally enjoy a symbiotic relationship with the host but can have adverse effects with local and systemic consequences. The small intestine constitutes a zone of transition between the sparsely populated stomach and the luxuriant bacterial flora of the colon. Regulation of the intestinal flora depends on complex interactions between many factors including secretion of gastric acid, intestinal motility, biliary and pancreatic secretions, local immunity, the surface glycocalyx and mucus layer, and diet. Microbial interactions are also important, and can involve alterations in redox potential, substrate depletion and production of substances such as bacteri-ocins that inhibit bacterial growth. The beneficial effect of the normal enteric flora include the competitive exclusion of potentially pathogenic organisms, and the production of nutrients such as short-chain fatty acids (which represent an important energy source for the colonic mucosa) and vitamins. Detrimental effects of the enteric flora include competition for calories and essential nutrients, particularly by bacteria located in the small intestine, and a capacity to damage the mucosa, in some circumstances causing or contributing to inflammatory bowel disease. These problems can be accentuated by interference with the physiological regulation of intraluminal bacteria allowing overgrowth by a normal resident, or colonisation by transient pathogens. The pathophysiological consequences may involve direct damage to the intestinal mucosa, and bacterial metabolism of intraluminal constituents, for example forming deconjugated bile acids and hydroxylated fatty acids which stimulate fluid secretion. Additional problems arise if there is interference with the mucosal barrier since this can result in increased passage of bacteria and bacterial products stimulating mucosal inflammation, while bacterial translocation can result in bacteraemia and septicaeniia. Problems associated with bacterial pathogens are illustrated by the properties of the spectrum of pathogenic Escherichia coli, some of which facilitate long-term colonisation by adherence to the surface or invasion of enterocytes.     

Serum amylase and isoamylase values in dogs with pancreatic disease

Serum amylase and isoamylase values were determined in three groups of dogs. The first group contained control dogs while the other groups contained dogs with confirmed exocrine pancreatic insufficiency and diabetes mellitus respectively. The trypsin-like immunoreactivity test was also carried out on sera from dogs with exocrine pancreatic disease (EPI). A significant difference was detected in the serum amylase values between the three groups which may be of limited diagnostic value. Dogs with EPI had values lower than normal while those with diabetes mellitus had values higher than control dogs. No evidence of exocrine pancreatic insufficiency was found in dogs with diabetes mellitus.     

Lymphocytic-Plasmacytic Enteritis in 24 Dogs

Lymphocytic-plasmacytic enteritis (LPE) was diagnosed by intestinal biopsy in 24 dogs with chronic small intestinal diarrhea. Vomiting, weight loss, and reduced appetite were frequent. Breed predispositions were not documented, although four patients were German Shepherd dogs. Hypoproteinemia, hypoalbuminemia, and hypoglobulinemia were common and most likely a result of protein-losing enteropathy. Other biochemical abnormalities were uncommon. Intestinal malabsorption was common. Neutrophilia (sometimes with increased band neutrophils), monocytosis, lymphopenia, and eosinopenia were the most consistent hematologic abnormalities. The severity of the lymphocytic-plasmacytic infiltration was not significantly different (P greater than 0.05) between regions of small intestine. However, the severity of cellular infiltration often varied among different regions of small intestine in the same dog. Changes in villous architecture and lacteal dilation were common. Intestinal nematode infestation was diagnosed in five dogs, and pancreatic exocrine insufficiency was diagnosed in one dog. In the remaining 18 dogs, besides LPE, no other associated or concurrent intestinal disease was diagnosed.     

A method for the simultaneous evaluation of exocrine pancreatic function and intestinal absorptive function in dogs.

Exocrine pancreatic function was evaluated in 13 dogs, using the chymotrypsin-labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA). This peptide releases p-aminobenzoic acid (PABA) in the presence of pancreatic chymotrypsin. The amount of PABA in blood or urine after BT-PABA administration then served as an index of pancreatic function. Similarly, a xylose absorption test has been described in the literature to evaluate absorptive function of the small intestine. Here, the pentose sugar d(+)xylose was given orally, and blood xylose concentrations were then measured at intervals. Since both tests were performed in nearly the same way, they were combined into a single test. A solution containing BT-PABA (30 mg/ml) and xylose (100 mg/ml) was administered perorally to dogs with and without pancreatic duct ligation. In the unoperated (control) dogs, peak blood concentrations for PABA occurred between 60 and 120 minutes and xylose concentrations were maximal between 30 and 90 minutes. Pancreatic duct ligation reduced PABA concentrations at 90 minutes to one-sixth of the values in control dogs. Xylose absorption, however, was not altered by pancreatic duct ligation. In this way, digestive and absorptive functions were both evaluated, using a single 90-minute test.     

Exocrine Pancreatic Insufficiency in the Dog: Historical Background,Diagnosis, and Treatment

This overview summarizes research performed during the last decades that has had an impact on the diagnosis and management of exocrine pancreatic insufficiency (EPI) in dogs. Pancreatic acinar atrophy is by far the most common cause for the maldigestion signs of canine EPI. The ability to diagnose pancreatic acinar atrophy in the subclinical phase before the development of total acinar atrophy and manifestation of clinical signs has offered new possibilities to study the pathogenesis of the disease. Diagnosis of exocrine pancreatic dysfunction is based on typical findings in clinical histories and clinical signs and is confirmed with pancreatic function tests. In recent years, the measurement of serum canine trypsin-like immunoreactivity has become the most commonly used pancreatic function test to diagnose canine EPI. Serum trypsin-like immunoreactivity measurement is species- and pancreas-specific. When clinical maldigestion signs of EPI appear, enzyme replacement therapy is indicated. Despite accurate enzyme supplementation, only a small portion of orally administered enzymes are delivered functionally intact into the small intestine. In dogs, the highest enzyme activity in the duodenum has been obtained with nonenteric-coated supplements: raw chopped pancreas or powdered enzymes. Aside from dietary enzyme supplements, dietary changes are often made to improve clinical response, but sometimes weight gain and stool quality remain suboptimal. Other medications for treatment of gastrointestinal tract signs are often used in such dogs with EPI. Antibiotics are the most common adjunctive medication. Of the antibiotics administered, tylosin is used in Finland almost exclusively.