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.     

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.     

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.     

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.     

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.     

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.     

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.     

Effect of intestinal inflammation on fecal elastase concentration in dogs

BACKGROUND: A commercially available ELISA kit for fecal elastase measurement can be used in the diagnosis of exocrine pancreatic insufficiency (EPI) in dogs. However, other causes of diarrhea also may affect fecal elastase concentration. OBJECTIVE: This study was undertaken to determine whether intestinal inflammation alters fecal elastase concentration in dogs. METHODS: Fecal elastase concentration was measured with an ELISA kit in the following groups of dogs: group 1 (n=16), control dogs, without gastrointestinal disease; group 2 (n=14), dogs with diarrhea and no histopathologic evidence of intestinal inflammation; and group 3 (n=12), dogs with diarrhea and histopathologic evidence of intestinal inflammation. Serum trypsin-like immunoreactivity (TLI) was determined in dogs with diarrhea to rule out EPI. RESULTS: All dogs in groups 2 and 3 had serum TLI concentrations >5 microg/L, ruling out EPI. No statistically significant difference was found in fecal elastase concentration among the 3 groups of dogs (P=.969). CONCLUSIONS: The results indicate that intestinal inflammation does not affect fecal elastase concentration, such that test results may be used to exclude a diagnosis of EPI even in animals with inflammatory bowel disease.     

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.     

Evaluation of serum bile acid concentrations for the diagnosis of portosystemic venous anomalies in the dog and cat

The serum concentration of bile acids was measured in dogs and cats with portosystemic venous anomalies (PSVA). In 14 dogs, the mean serum bile acid concentration after 12 hours of fasting was 61.7 +/- 68.7 mumol/L (normal, 2.3 +/- 0.4 mumol/L (SEM) and when measured 2 hours after a meal in 15 dogs was 229.9 +/- 87.7 mumol/L (normal, 8.3 +/- 2.2 mumol/L). The fasting serum bile acid concentration was within the normal range in 5 of 14 dogs. The postprandial concentration was determined in 3 of the 5 and in each case increased more than tenfold above the fasting value. The mean fasting serum bile acid concentration in 4 cats was 24.4 +/- 10.1 mumol/L (normal, 1.7 +/- 0.3 mumol/L) and in 2 of the cats increased to a mean of 120.6 mumol/L (normal, 8.3 +/- 0.8 mumol/L) 2 hours after feeding. The bile acid values in patients with PSVA were correlated with values for blood ammonia content, sulfobromophthalein (BSP) retention, and results of conventional tests of hepatic function. Bile acid concentrations were more sensitive than abnormalities in serum enzyme activities or BSP retention and equal in sensitivity to the ammonia tolerance test in detecting hepatobiliary insufficiency. Bile acid measurements were accomplished with less inconvenience to the patient and clinician, than tests of BSP excretion or ammonia tolerance. Used in combination with conventional laboratory tests for hepatic disease, pre- and postprandial serum bile acid concentrations appear to be a sensitive and specific indicator of hepatobiliary dysfunction of value in the diagnosis of PSVA in the dog and cat.     

Relationships between diet and malabsorption in dogs

Abnormalities affecting the pancreas or small intestine can result in malabsorption and diarrhoea by interfering with either the degradative or absorptive phases in the handling of one or more nutrients. Diet may be involved in the pathogenesis of certain disorders and can also influence the nature and severity of the clinical manifestations of gastrointestinal disease. Exocrine pancreatic insufficiency can have serious nutritional consequences as the pancreas plays a crucial role in the degradation of the main dietary constituents. Whereas gastrointestinal peptidases help compensate for pancreatic protease deficiencies, malabsorption of carbohydrate and fat occurs and can result in osmotic and secretory diarrhoea, respectively. Small intestinal disease can result in malabsorption by interference with either the number or functioning of individual enterocytes. Diarrhoea may be due to stimulated secretion and diminished absorption of fluid and electrolytes, and also to the osmotic effects of small molecules, particularly carbohydrates, that remain in the lumen. Specific therapy depends on the disease. Dietary management is also important, for example with a restricted fat diet containing highly digestible carbohydrate and a high quality protein source. Where a specific dietary sensitivity is suspected, such as gluten-enteropathy, a hypoallergenic diet may prove particularly valuable.     

Sensitivity and specificity of canine serum total amylase and isoamylase activity determinations.

Serum isoamylases were determined prospectively in dogs with pancreatic and extrapancreatic diseases. Mean serum isoamylase determinations were significantly different (p less than 0.05) between normal dogs and dogs with pancreatitis and exocrine pancreatic insufficiency. The sensitivity of serum isoamylase determination exceeded that of total amylase activity for the diagnosis of pancreatitis. Serum isoamylase determinations were less influenced by extrapancreatic diseases compared to total amylase activity when used in the diagnosis of pancreatic disease. Neither serum isoamylase determination nor total amylase activity had adequate sensitivity to support their use in the diagnosis of exocrine pancreatic insufficiency. There were significant (p less than 0.05) linear correlations between isoamylase determinations, total amylase activity, and trypsin-like immunoreactivity concentration.     

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 intestinal carbohydrate malabsorption in the dog by pulmonary hydrogen gas excretion

Breath H2 was measured for the assessment of intestinal carbohydrate absorption in healthy, fasted dogs before and after the ingestion of carbohydrate test meals. The dogs were fed lactulose, xylose, glucose, a hypoallergenic diet, or the hypoallergenic diet supplemented with rice, corn, or wheat flour. Breath samples for H2 analysis were collected by an interval-sampling technique during tidal breathing and were analyzed by thermal conductivity gas chromatography. Pulmonary H2 excretion in fasted dogs never exceeded 1 part per million (molecules of H2 per 10(6) molecules of air). Breath H2 excretion after the ingestion of 12.5 g of glucose, a completely absorbed monosaccharide, was not significantly different (P greater than 0.05) from that during fasting; however, ingestion of 12.5 g of xylose, an incompletely absorbed pentose, significantly increased (P less than 0.001) breath H2 excretion. After ingestion of 12.5, 25, or 50 g of lactulose, a nonabsorbable disaccharide, pulmonary H2 excretion increased significantly (P less than 0.001) over fasting amounts and the increases were different (P less than 0.001) from one another. Increases in breath H2 excretion correlated (r = 0.97) with increases in lactulose dose. Breath H2 excretion after the ingestion of the hypoallergenic diet did not significantly (P greater than 0.05) differ from that after fasting. The addition of rice flour to this diet did not significantly (P greater than 0.05) increase H2 production. However, the addition of wheat or corn flour to this diet significantly (P less than 0.001) increased breath H2 excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Digestion of bentiromide and absorption of xylose in healthy cats and absorption of xylose in cats with infiltrative intestinal disease

The digestion of bentiromide and the absorption of D-xylose was measured in 17 clinically healthy cats. The plasma xylose concentrations of the healthy cats were compared with values from 9 cats with diffuse infiltrative intestinal disease. The cats were administered 16.7 mg of bentiromide/kg and 0.5 g of xylose/kg via a stomach tube. Plasma samples were obtained before administration and 30, 60, 90, and 120 minutes after administration. The maximum mean plasma p-aminobenzoic acid concentration occurred at 60 minutes, with a value of 386 +/- 134 micrograms/dl (mean +/- SD). The maximum mean plasma xylose concentration also occurred at 60 minutes, with a value of 26.0 +/- 9.2 mg/dl. Plasma concentrations of p-aminobenzoic acid and xylose were lower in healthy cats than those reported for healthy dogs. There was no significant difference between xylose concentrations in healthy cats and cats with infiltrative intestinal disease.     

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.     

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.     

Pancreatic Degenerative Atrophy and Chronic Pancreatitis in Dogs a Comparative Study of 60 Cases

During the years 1977–1980 60 cases of non-neoplastic chronic exocrine pancreatic disease in dogs were investigated clinically and pathologically. The disorders were clinically divided into pancreatic degenerative atrophy (PDA) and chronic pancreatitis. Fifty dogs had PDA and 45 of them were German shepherd dogs. The PDA cases formed both clinically and pathologically a homogeneous group except for 1 case. All the dogs had maldigestion and protease activity was absent from the faeces. General inanition and highly atrophic pancreas were the most typical macroscopic findings. Histologically the exocrine pancreas contained atypical acinar tissue and mononuclear cell infiltrations. Five of the dogs died spontaneously, 4 of them had intestinal torsion and 1 had paralytic ileus.There were 10 dogs with chronic pancreatitis. This group was rather heterogeneous both clinically and pathologically. The pancreas was slightly enlarged and the consistency was firm. The histologic picture was one of fibrous tissue proliferation and inflammatory cell infiltrations in the interstitium. The dogs nutritional state as well as faecal protease activity were normal.     

Exocrine Pancreatic Insufficiency in the Dog: Breed Associations,Nutritional Considerations,and Long-term Outcome

Canine exocrine pancreatic insufficiency (EPI) is an alimentary tract disorder causing malabsorption and debilitations in affected individuals. This article covers predisposing factors to EPI and response to therapy. Although relatively easy to diagnose, knowledge of breed predispositions (and also of those breeds where the disease is less common) can guide the clinician. Numerous studies have examined therapy for EPI, and a key finding is the variability in response among affected dogs. This implies that close monitoring and individual tailoring of therapy is needed to maximize the chance of success. Important factors affecting outcome are the choice of enzyme preparation, presence of hypocobalaminemia, and the response to the first 2 to 3 months of therapy.