Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency is thought to occur rarely in cats. This assumption has been made based on the lack of a specific test for this disease in the cat. Clinical data from the 1st 20 cats with serum feline trypsin-like immunoreactivity (fTLI) concentrations < or = 8 microg/L are presented. In 17 of these 20 cats compelling evidence for a diagnosis of exocrine pancreatic insufficiency (EPI) was present and in the remaining 3 supportive evidence for a diagnosis of EPI was available. The conclusion was made that serum fTLI concentration is a specific test for EPI in the cat.     

Serum isoamylase values in normal dogs and dogs with exocrine pancreatic insufficiency

Estimations were made of the serum isoamylase values of normal dogs and of dogs with confirmed exocrine pancreatic insufficiency. A statistically significant difference was demonstrated between the two groups in respect of the values of one of the isoamylase fractions measured. Further study has confirmed that canine salivary tissue lacks amylase activity and that the source of the isoamylase fractions was the pancreas.This knowledge has potential value in the diagnosis of canine exocrine pancreatic insufficiency.     

Subclinical exocrine pancreatic insufficiency in dogs

OBJECTIVE: To study progression of autoimmune-mediated atrophic lymphocytic pancreatitis from the subclinical to the clinical phase (exocrine pancreatic insufficiency [EPI]) and determine whether progression of the disease could be halted by treatment with immunosuppressive drugs. DESIGN: Randomized controlled trial. ANIMALS: 20 dogs with subclinical EPI. PROCEDURE: Diagnosis of subclinical EPI was determined on the basis of repeatedly low serum trypsin like-immunoreactivity (TLI) in dogs with no signs of EPI. Laparotomy was performed on 12 dogs with partial acinar atrophy and atrophic lymphocytic pancreatitis. A treatment group (7 dogs) received an immunosuppressive drug (azathioprine) for 9 to 18 months, and a nontreatment group (13) received no medication. RESULTS: During the subclinical phase, serum TLI was repeatedly low (< 5.0 microg/L). Although a few dogs had nonspecific gastrointestinal tract signs, they did not need diet supplementation with enzymes. While receiving immunosuppressive medication, treated dogs had no clinical signs of EPI, but within 2 to 6 months after treatment was stopped, 2 dogs had signs of EPI, and diet supplementation with enzymes was started. Five of the 13 untreated dogs needed diet supplementation with enzymes within 6 to 46 months. During follow-up of 1 to 6 years, 3 of the 7 treated dogs and 8 of the 13 untreated dogs did not need continuous diet supplementation with enzymes. CONCLUSIONS AND CLINICAL RELEVANCE: Progression of atrophic lymphocytic pancreatitis varied widely. The subclinical phase may last for years and sometimes for life. The value of early treatment with an immunosuppressive drug was questionable and, because of the slow natural progression of the disease, cannot be recommended.     

Circulating concentrations of trypsin-like immunoreactivity and activities of lipase and amylase after pancreatic duct ligation in dogs

The possibility that assay of circulating trypsin-like immunoreactivity (TLI) could assist in the diagnosis of acute pancreatitis in dogs has been examined by assaying plasma TLI concentrations after pancreatic duct ligation and comparing the results with plasma activities of lipase and amylase. Venous blood samples were obtained from 8 dogs before surgery, then daily for 5 days and at 14 days after ligation of pancreatic ducts. Plasma concentrations of TLI increased within 24 hours and tended to peak before and to decrease more rapidly than activities of lipase and amylase, remaining greater than the control range for 5 days in all but 2 dogs. Plasma lipase and amylase activities increased together and remained greater than the control range in all dogs for 5 days after surgery. Regression analysis of all postoperative data indicated significant correlations between concentration of TLI and lipase activity (r = 0.67, P less than 0.001), concentration of TLI and amylase activity (r = 0.53, P less than 0.001), and between lipase and amylase activities (r = 0.74, P less than 0.001). These findings suggested that assay of TLI may provide an early indication of acute pancreatitis in dogs. Because TLI is specifically pancreatic in origin, high plasma TLI concentration may prove a more reliable indicator of clinical pancreatitis than high activities of amylase or lipase, which may be derived from extrapancreatic tissues.     

Oral bleeding associated with pancreatic enzyme supplementation in three dogs with exocrine pancreatic insufficiency

Three dogs with exocrine pancreatic insufficiency developed oral bleeding during treatment with pancreatic enzyme supplements. According to the owners of the dogs, bleeding from the oral cavity developed during or shortly after consumption of meals containing the pancreatic enzyme supplement. Oral bleeding stopped in all dogs when owners reduced the dose of the pancreatic enzyme supplement. In 2 dogs, the decrease in the dose of the pancreatic enzyme supplement did not affect fecal consistency. However, in the third dog, the decrease in dose led to a recurrence of clinical signs. Findings in these dogs suggest that high doses of pancreatic enzyme supplements can cause oral bleeding in dogs with pancreatic insufficiency, but that oral bleeding can be successfully managed by dose reduction in most dogs.     

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.     

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.     

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.     

High serum trypsin-like immunoreactivity secondary to pancreatitis in a dog with exocrine pancreatic insufficiency

A 13-year-old spayed Doberman Pinscher with acute vomiting of 24 hours' duration and concurrent 2-week history of polyphagia with weight loss had diabetic ketoacidosis complicated by acute pancreatitis and exocrine pancreatic insufficiency. Diagnostic testing for exocrine pancreatic insufficiency, by determining serum trypsin-like immunoreactivity, revealed an unexpectedly high result when a low result was anticipated. High trypsin-like immunoreactivity was attributed to acute pancreatic inflammation.     

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.     

Observations on exocrine pancreatic insufficiency in a family of English setter dogs

The aim of this paper is to report serum trypsin-like immunoreactivity (TLI) concentrations in the progeny of a pair of English setters. These dogs had a history of producing puppies with a high prevalence of exocrine pancreatic insufficiency (EPI) secondary to either congenital deficiency or early onset juvenile atrophy of pancreatic acinar cells. Serum TLI concentrations in the clinically healthy parents of the puppies with EPI were normal, as were serum TLI concentrations in the unaffected puppies. However, serum TLI concentrations were extremely low (less than 1 μg/litre) in three puppies at eight to 12 weeks of age when clinical signs of EPI were present. In addition, one of the three puppies, with low TLI concentrations at eight weeks of age, had serum TLI concentrations of 0.7 μg/litre at two weeks of age even though no clinical signs were evident at that time. These results suggest that serum TLI assay may be a useful diagnostic aid in identifying puppies at a very early age with this unusual form of EPI.     

Effects of diet on clinical signs of exocrine pancreatic insufficiency in dogs

OBJECTIVE: To assess the effects of dietary modification on clinical signs of exocrine pancreatic insufficiency (EPI) in dogs. DESIGN: Blinded randomized crossover study. ANIMALS: 21 dogs with EPI. PROCEDURE: Dogs were fed the diet they received at home for 2 weeks. Thereafter, they received 3 special diets (a high-fat diet, a high-fiber diet, and a highly digestible low-residue diet) for 3 weeks each. Owners scored dogs daily for the last 2 weeks of each 3-week period for severity of 6 clinical signs including appetite, defecation frequency, consistency of feces, borborygmus, flatulence, and coprophagia. An EPI index was calculated for each dog by adding the daily scores for each clinical sign. RESULTS: Significant differences in daily EPI indices among diets were observed in 20 dogs. The original diet appeared to be the most suitable in 8 dogs, whereas the high-fat diet was most suitable in 5 dogs, the high-fiber diet was most suitable in 4 dogs, and the low-residue diet was most suitable in 2 dogs. In 1 dog, the lowest EPI index score was the same during the original diet and the high-fat diet feeding periods. One dog did not complete the feeding period for the high-fiber diet. Differences in mean EPI indices among diets were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that responses to different diets varied among individual dogs. Because responses to the feeding regimens were unpredictable, it is suggested that feeding regimens be individually formulated for dogs with EPI.     

Serum amylase and lipase activities after exploratory laparotomy in dogs

Serum amylase and lipase activities and creatinine concentration were determined before surgery, and at 1 and 2 days after exploratory laparotomy in 24 dogs. Examination of all viscera was done during each laparotomy, but a surgical procedure was not performed. The mean serum activities for lipase were: before surgery, 0.71 (0.0 to 2.0) Cherry Crandall units (CCU)/L; 1 day after surgery, 2.1 (0.0 to 4.5) CCU/L; and 2 days after surgery, 1.19 (0.0 to 3.9) CCU/L. The mean serum activities for amylase were: before surgery, 1,958 (1,027 to 3,426) IU/L; 1 day after surgery, 1,538 (937 to 2,659) IU/L; and 2 days after surgery, 1,663 (1,066 to 2,274) IU/L. Serum creatinine concentrations before surgery, 1 day after surgery, and 2 days after surgery were 0.88 (0.2 to 1.7) mg/dl, 0.78 (0.4 to 1.3) mg/dl, and 0.78 (0.3 to 1.3) mg/dl, respectively. Mean preoperative, day-1, and day-2 serum amylase activities and serum creatinine concentrations did not differ significantly from each other. Mean preoperative and day-2 serum lipase activities did not differ significantly; however, mean serum lipase activity was significantly greater when day 1 activities were compared with preoperative activities (P = 0.0002). Post-mortem examinations revealed no gross or histologic evidence of pancreatitis in any dog. The results of this study show that a 3 or more fold increase in serum lipase activity may occur after routine exploratory laparotomy in dogs without clinical signs or gross evidence of pancreatitis. Histologic evidence of pancreatitis was not found in the right pancreatic lobes in any dog.     

Diagnosis of canine exocrine pancreatic insufficiency by the assay of serum trypsin-like immunoreactivity

A radioimmunoassay for canine serum trypsin-like immunoreactivity (TLI) has been developed and evaluated for use in the diagnosis of exocrine pancreatic insufficiency (EPI). The maximum fasting TLI concentration in 14 dogs with EPI was 1.8 μg/l, compared with a minimum value of 7.0 μg/l in a control group of 75 dogs. The measurement of serum TLI therefore provides a sensitive test for the diagnosis of EPI in the dog.     

Serum values of amylase and pancreatic lipase in healthy mature dogs and dogs with experimental pancreatitis

Serum values of amylase and pancreatic lipase were determined by the iodometric and the turbidimetric methods, respectively, in 44 mature healthy dogs and in 8 dogs with experimentally induced pancreatitis (plus 1 sham-operated control). Serum value of amylase in mature healthy dogs varied from 250 to 1,500 Caraway units/dl and that of pancreatic lipase varied from 0 to 50 IU/L. Maximal serum values of amylase and pancreatic lipase in the dogs with experimentally induced pancreatitis varied from 4,540 to 14,000 Caraway units/dl and 325 to 810 IU/L, respectively. Following pancreatic damage, serum values of amylase and pancreatic lipase increased rapidly in the 8 dogs and ran parallel to each other in 6 of the 8 dogs studied. However, the serum value of amylase returned to within normal range earlier than the serum value of pancreatic lipase in 2 dogs; the reverse was true in 2 other dogs.