Effects of exocrine pancreatic insufficiency and replacement therapy on the bacterial flora of the duodenum in dogs

The influence of pancreatic secretions on the bacterial flora of the small intestine in 6 dogs was investigated by determining effects of exocrine pancreatic insufficiency on numbers and types of bacteria in duodenal juice, and by examining the subsequent response to dietary supplementation with bovine pancreatic extract. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and was confirmed by indirect assessment of exocrine pancreatic function. Duct ligation was followed by large increases (P less than 0.01) in total numbers of bacteria, reflecting increased numbers particularly of Lactobacillus spp and Streptococcus spp, in 3 dogs accompanied by obligate anaerobes. Total numbers of aerobes and anaerobes decreased markedly (P less than 0.05) after supplementation with bovine pancreatic extract to values that were not significantly different from those determined before duct ligation. Exocrine pancreatic insufficiency therefore resulted in small intestinal bacterial overgrowth that was reversed by pancreatic replacement therapy, indicating that pancreatic secretions can have an important influence on the small intestinal bacterial flora of dogs.     

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.     

Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs.

The effects of pancreatic duct anastomosis to stomach (stomach group) or duodenum (duodenal group) on pancreatic function were examined in dogs following two thirds pancreatectomy. Normal fasting blood glucose concentrations were maintained in both groups despite significant reductions in glucose tolerance in the stomach group, and reductions in fasting insulin and insulin peak response in both groups. Pancreatic exocrine function was significantly decreased in both groups, though plasma p-aminobenzoic acid (PABA) concentrations were generally higher in the duodenal group. A correlation was found between plasma trypsin-like immunoreactivity (TLI) and pancreatic weight. These results indicate that anastomosis of the pancreas to bowel can be undertaken with minimal postoperative complications and that the site of the anastomosis influences pancreatic function. They suggest that preservation of more than one third of the pancreas is required for optimal function. The complementary information provided by the PABA and TLI tests suggests their dual application will be clinically useful for the detection and characterisation of naturally occurring pancreatic diseases.     

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.     

Pancreatic adenocarcinoma in a dog with a maldigestion syndrome

Maldigestion caused by a pancreatic enzyme insufficiency was diagnosed in a 10-year-old Scottish Terrier on the basis of clinical signs and gastrointestinal function test results. The histologic diagnosis was pancreatic adenocarcinoma. Maldigestion is an unusual manifestation of this malignancy, particularly in the absence of other clinical signs. However, pancreatic neoplasia should be considered in aged dogs that develop exocrine insufficiency.     

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.     

Evaluation of Fecal Elastase and Serum Cholecystokinin in Dogs with a False Positive Fecal Elastase Test

Background: An assay for the measurement of pancreatic elastase in dog feces has been introduced. Hypothesis/Objectives: The goal of this study was to evaluate the rate of false‐positive fecal‐elastase test results in dogs with suspected exocrine pancreatic insufficiency (EPI) and to assess serum cholecystokinin (CCK) concentrations in dogs with a false positive fecal elastase test result. Animals: Twenty‐six fecal and serum samples from dogs suspected of EPI, for which samples had been submitted to a commercial laboratory (Vet Med Labor) for analysis. Methods: Prospective study. Serum trypsin‐like immunoreactivity (TLI) was measured in 26 dogs with a decreased fecal elastase concentration of <10 μg/g feces. Serum CCK concentrations were measured in 21 of these dogs. Results: Of 26 dogs with a decreased fecal elastase concentration, 6 (23%) had serum TLI concentrations within or above the reference range. Serum CCK concentrations were significantly higher in dogs with a true positive fecal elastase test result (median: 1.1 pmol/L; range: 0.1–3.3 pmol/L) than in those with a false positive fecal elastase test result (median: 0.1 pmol/L; range: 0.1–0.9 pmol/L; P value = .0163). Conclusions and Clinical Importance: The rate of false positive fecal elastase test results was high in this group of dogs, suggesting that diagnosis of EPI must be confirmed by other means. The decreased CCK concentration in dogs with a false positive fecal elastase test result could suggest that false positive results are because of decreased stimulation of exocrine pancreatic function caused by other conditions.     

Quantitative assessment of fat absorption and its diagnostic value in exocrine pancreatic insufficiency

A new method of quantifying fat absorption based on the estimation of serum triglyceride levels is described. When long chain triglyceride (LCT) was fed to normal dogs a significant elevation of serum triglyceride concentration was recorded which was not observed in dogs with exocrine pancreatic insufficiency. When the test was repeated on the dogs with pancreatic insufficiency using the LCT together with lipase the serum triglyceride concentration increased, suggesting the failure in the initial test was caused by a deficiency in pancreatic lipase. Feeding medium chain triglyceride (MCT) did not raise the serum triglyceride levels in normal dogs.     

Comparison of the effect of caerulein and testmeal on exocrine pancreatic secretion in the dog

Small doses of caerulein (10, 20, 40, 100 ng/kg/h) were given to conscious dogs with chronic duodenal and gastric fistulas, and the exocrine pancreatic response was compared with that obtained by a testmeal. Maximal protein and bicarbonate secretion varied between 20 and more than 100 ng/kg/h, depending on the individual animal. Testmeal-stimulated pancreatic secretion was approximately equivalent to that achieved with 10 ng caerulein/kg/h. Plasma secretin levels did not change significantly during testmeal stimulation.     

Serum lipase activities and pancreatic lipase immunoreactivity concentrations in dogs with exocrine pancreatic insufficiency

OBJECTIVE: To determine serum lipase activities and pancreatic lipase immunoreactivity (PLI) concentrations in dogs with exocrine pancreatic insufficiency (EPI). ANIMALS: 74 healthy dogs and 25 dogs with EPI. PROCEDURES: A diagnosis of EPI was made on the basis of clinical signs, low serum trypsin like immunoreactivity (TLI) concentration, and response to treatment with enzyme replacement. Median values for fasting serum lipase activity and serum PLI concentrations were compared between the 2 groups with a Mann-Whitney U test. RESULTS: Median fasting serum lipase activity was not significantly different between dogs with EPI (366.0 U/L) and healthy dogs (294.5 U/L), and only 1 dog with EPI had a serum lipase activity less than the lower limit of the reference range. Median serum PLI concentration was significantly lower in dogs with EPI (0.1 microg/L) than in healthy dogs (16.3 microg/L). All dogs with EPI had serum PLI concentrations less than the lower limit of the reference range. CONCLUSION AND CLINICAL RELEVANCE: Serum lipase activity is not limited to the exocrine pancreas in origin, whereas serum PLI is derived only from the exocrine pancreas. Unlike in serum TLI concentrations, there was a small degree of overlap in serum PLI concentrations between healthy dogs and dogs with EPI. Serum TLI concentration remains the test of choice for diagnosis of EPI.     

Collection of pancreatic exocrine secretions by formation of a duodenal pouch in cattle.

Collection of exocrine pancreatic secretions from cattle by use of a single-unit cannula was performed. The major advantage of the cannula was simple technical management. A small pouch of the duodenum into which the major pancreatic duct drains was formed. Continuity of the duodenum was reestablished by end-to-end anastomosis. A side arm of the cannula was inserted into the pouch to collect exocrine secretions, and the main portion of the cannula was placed cranial to the anastomosis to return pancreatic secretions to the small intestine between collection periods. The accessory pancreatic duct was ligated in 2 of 4 cattle to evaluate possible secretory contribution from this source. All cattle remained healthy after cannulation, and cattle gained approximately 100 kg of body weight in the 5 months after surgery. The mean secretory rate for exocrine pancreatic secretion in cattle was 106 +/- 6.8 ml/h. There was no effect of feeding on the pattern of secretion nor were there significant differences between cattle. A fistula formed between the pouch and duodenum approximately 120 days after surgery in the first 2 cattle used. Development of fistulas was prevented for 300 days in subsequently prepared cattle by use of surgical mesh around the cannulas, leading to functional cannulation sites. Preparation of a duodenal pouch appeared useful for long-term studies of pancreatic exocrine secretion in cattle.     

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.     

Exocrine pancreatic insufficiency in the cat

While exocrine pancreatic insufficiency (EPI) is a well-documented functional disease of the pancreas in dogs, only a few reports characterize EPI in cats and no information is available on cats diagnosed with a function test from Europe. The present case series describes and discusses the clinicopathologic findings, diagnostics and therapy in 5 cats (18 months to 16 years) with EPI from Switzerland.     

Liver biochemical and histopathological findings in dogs with experimentally induced exocrine pancreatic insufficiency

Routine liver biochemical parameters were evaluated in 8 dogs with exocrine pancreatic insufficiency (EPI) induced by surgical ligation of the pancreatic duct and the pancreatic branch of the pancreaticoduodenal artery and confirmed with the trypsin-like immunoreactivity test. Eight additional dogs were used as healthy controls. Data collection began at the 4th week postoperatively and continued weekly to the 21st week. In the dogs with EPI, the serum activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were consistently elevated. The serum total and conjugated bilirubin concentrations remained within normal limits throughout the experimental period. Histopathological study revealed hepatic lipidosis in the dogs with EPI. Therefore, since this condition seems to be an additional consequence of EPI in dogs, laboratory evaluation of dogs with EPI must include assessment of liver function, to determine if additional or different therapeutic measures are indicated.     

Immunocytochemical component of endocrine cells in pancreatic islets of horses

The endocrine cell components in the pancreatic islets of the following 4 pancreatic regions of the horse were investigated by immunohistochemical methods: lobus pancreatis sinister (left lobe); lobus pancreatis dexter (right lobe); and 2 regions of Corpus pancreatis (body), the duodenal lobe which lies along the cranial duodenal flexure and descending duodenum, and the intermediate lobe which is situated around the portal vein. The islets in the left and intermediate lobes contained a central mass of glucagon cells surrounded by insulin cells, a few somatostatin cells and sporadic pancreatic polypeptide (PP) cells. On the other hand, the islets in the duodenal lobe were small in size compared with the other 3 regions, and were predominant in insulin and pancreatic polypeptide (PP) cells, but almost lacked in glucagon cells. These findings suggested that the duodenal lobe was derived from the ventral pancreatic primordium, and the left and intermediate lobes were originated from the dorsal pancreatic primordium. In the right lobe, the composition and distribution of the islet cells were almost the same as those in the left and intermediate lobes, but there were several lobules containing numerous PP cells as seen in the duodenal lobe.     

Ileal exposure to pig pancreatic juice and bile inhibit exocrine pancreatic secretion in pigs

The mechanisms involved in the down regulation of the exocrine pancreas are still not fully elucidated. The purpose of the present study was to examine the effect of duodenal and ileal exposure to pancreatic enzymes and bile on pancreatic secretion. Experiments were performed with pigs fitted with pancreatic duct, ileal and jugular vein catheters, and duodenal T-shaped cannula. A negative feedback regulation of pancreatic secretion was found for both duodenal and ileal delivery of pancreatic juice. Pancreatic secretion was unaffected by duodenal delivery of bile and bile salts, while ileal delivery of bile and bile salts lowered it. On the other hand, pancreatic secretion was increased by duodenal loading of commercial non- or activated pancreatic enzyme preparations, thus probably recognised as dietary protein. Plasma cholecystokinin (CCK) level was lowered only by duodenal delivery of pancreatic juice. In conclusion, the results prove the existence of negative feedback mechanism regulating pancreatic secretion dependent on the presence of pure pancreatic juice or bile at the ileal level. The mechanism at the duodenal level is exclusively sensitive to pure pancreatic juice.     

Sensitivity and specificity of radioimmunoassay of serum trypsin-like immunoreactivity for the diagnosis of canine exocrine pancreatic insufficiency

Concentrations of serum trypsin-like immunoreactivity (TLI) measured by radioimmunoassay were low (less than 1.9 micrograms/L) in 25 dogs with exocrine pancreatic insufficiency (EPI), compared with 100 clinically normal (control) dogs (5.2 to 34.0 micrograms/L; P less than 0.001; sensitivity, 100%). Serum TLI concentrations (5.5 to 35.0 micrograms/L) in a group of 50 dogs with small intestinal disease (SID) were not significantly different from those of control dogs, values being greater than the lower limit of the control range in all cases (specificity, 100%). Results of bentiromide (N-benzoyl-L-tyrosyl-p-aminobenzoic acid [BT-PABA]) tests and fecal proteolytic activity (determined by use of an azocasein substrate) were abnormal in 21 of 22 dogs with EPI (sensitivity, 95%). Bentiromide test results were subnormal in 13 of 35 dogs with SID (specificity, 63%), whereas fecal proteolytic activity was subnormal in 7 of 34 dogs with SID (specificity, 79%). It was concluded that assay of serum TLI is a highly sensitive and specific test for the identification of dogs with EPI.     

Histologic assessment and grading of the exocrine pancreas in the dog.

Histologic grading schemes for canine inflammatory conditions are sparse, and in the case of the canine pancreas, have not been previously described. In a previous study, we determined that histologic lesions of the exocrine pancreas occurred much more frequently than gross lesions. The intention of the current study was to develop a histologic grading scheme for nonneoplastic lesions following extensive assessment of the exocrine pancreas from dogs presented for necropsy examination. The parameters of the proposed scheme include neutrophilic inflammation, lymphocytic inflammation, pancreatic necrosis, pancreatic fat necrosis, edema, fibrosis, atrophy, and hyperplastic nodules. In this case series, the most common lesion was pancreatic hyperplastic nodules (80.2%), followed by lymphocytic inflammation (52.5%), fibrosis (49.5%), atrophy (46.5%), neutrophilic inflammation (31.7%), pancreatic fat necrosis (25.7%), pancreatic necrosis (16.8%), and edema (9.9%). Only 8 of the 101 animals had no evidence of any of the lesions in any of the sections examined. Fibrosis, atrophy, and/or lymphocytic infiltration most commonly accompanied nodules. Neutrophilic inflammation, when present, was often associated with necrosis (pancreatic necrosis, pancreatic fat necrosis, or both) and occasionally with hyperplastic nodules. The utilization of a grading scheme for exocrine pancreatic lesions will be useful in advancing the classification of exocrine pancreatic disease in the dog, which may lead to multicenter studies of exocrine pancreatic disorders in the dog and in other species.     

Localization of pancreatic inflammation and necrosis in dogs

Few studies of the prevalence of histologic lesions of the exocrine pancreas in dogs have been reported, and none of them systematically evaluate the localization of these lesions. The purpose of this study was to describe the anatomic localization of pancreatic inflammation, necrosis, and fibrosis in dogs presented for postmortem examination. Seventy-three pancreata from dogs presented for postmortem examination were evaluated and investigated for the presence of suppurative inflammation (SI), pancreatic necrosis (PN), and lymphocytic inflammation (LI). Sections that showed evidence of SI, PN, or LI also were evaluated for pancreatic fibrosis (F). The tendency for a preferred localization for SI, PN, and LI was evaluated by chi-square analysis. A total of 47 pancreata with histologic evidence of pancreatitis (SI, PN, or LI; F alone was not considered evidence of pancreatitis) were identified. Twenty-four (51.1%) had SI, 23 (48.9%) had PN, and 34 (72.3%) had LI. Of the 47 dogs with SI, PN, or LI, 28 (59.6%) had F. The distribution of SI, PN, and LI between the right and the left limb of the pancreas and among the 5 anatomic regions was random, based on a goodness-of-fit test. We conclude that pancreatic inflammation tends to occur in discrete areas within the pancreas rather than diffusely throughout the whole organ. These findings suggest that a single biopsy is insufficient to exclude subclinical pancreatitis and that there is no preferred site for pancreatic biopsy collection unless gross lesions are apparent.     

Juvenile Pancreatic Atrophy in Greyhounds: 12 Cases (1995–2000)

Background: This study describes compound failure of the endocrine and exocrine pancreas in Greyhounds, a condition that has not been reported in the veterinary literature.
Objective: To describe the clinical and pathologic findings in 12 Greyhounds with juvenile pancreatic atrophy.
Animals: Ten Greyhounds presented for necropsy examination and 2 sibling Greyhounds presented for clinical evaluation before necropsy, all with a history of small-bowel diarrhea.
Procedures: Retrospective study of laboratory and pathologic findings in 12 Greyhounds, including serum trypsin-like immunoreactivity assays, oral glucose tolerance testing, and serum anti-insulin antibody concentrations.
Results: Gross pancreatic atrophy was found in all 12 dogs. Histopathologic lesions were found in both the endocrine and exocrine pancreas and included acinar cell apoptosis, zymogen granule loss, cytoplasmic clearing or vacuolar change, lobular atrophy, islet loss, and lymphocytic or lymphoplasmacytic pancreatitis. Antemortem test results on the 2 Greyhound puppies indicated concurrent exocrine pancreatic insufficiency (EPI) and insulin-dependent diabetes mellitus (IDDM).
Conclusions and Clinical Importance: Compound failure of the exocrine and endocrine pancreas is rarely reported in dogs and neither disease is well recognized in the Greyhound. This condition is of potential economic importance to the Greyhound racing industry.