RESUMO
BACKGROUND: Several studies have revealed that exocrine pancreatic insufficiency (EPI) is an inherited disease in German Shepherd Dogs (GSDs). Pedigree analyses have suggested an autosomal recessive inheritance model. OBJECTIVE: Test mating of 2 dogs with EPI. ANIMALS: A sire and dam purebred GSD both with EPI and a litter of 6 puppies. METHODS: Test mating and long-term follow-up of offspring. The pancreas was biopsied via laparotomy on 26 occasions. Serum trypsin-like immunoreactivity was measured. Study was approved by Animal Ethics Committee. RESULTS: During the 12-year study period only 2 of the 6 offsprings developed pancreatic acinar atrophy (PAA). In 1 puppy, end-stage PAA and in the other puppy partial PAA was diagnosed. CONCLUSIONS AND CLINICAL IMPORTANCE: PAA is not a congenital disease in GSDs. This study provided evidence that PAA is not inherited in a simple autosomal recessive fashion.
Assuntos
Doenças do Cão/genética , Insuficiência Pancreática Exócrina/veterinária , Animais , Cães , Insuficiência Pancreática Exócrina/genética , Feminino , Predisposição Genética para Doença , MasculinoRESUMO
In pancreatic acinar atrophy (PAA) a selective destruction of digestive enzyme-producing acinar cells leads to maldigestion signs typical of exocrine pancreatic insufficiency (EPI). Although the clinical disease is well-known, the etiopathogenesis of PAA has been long remained obscure. German shepherd dogs and rough-coated Collies with PAA show similar genetic, clinical and pathological findings indicating a similar etiopathogenesis of the disease in these two breeds. In this review article the etiopathogenesis of PAA is discussed, including the current suggestion of autoimmune nature of the disease. The diagnostic methods for detection both early and end-stage exocrine pancreatic dysfunction are described, as well as the treatment options and prognosis.
Assuntos
Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Pâncreas/patologia , Pancreatite/veterinária , Animais , Atrofia/diagnóstico , Atrofia/terapia , Atrofia/veterinária , Doenças do Cão/sangue , Doenças do Cão/genética , Cães , Pancreatite/diagnóstico , Pancreatite/terapia , LinhagemRESUMO
The most common cause for the clinical signs of exocrine pancreatic insufficiency (EPI) in dogs is pancreatic acinar atrophy (PAA). In the subclinical phase of EPI, before total atrophy occurs, exocrine pancreas is affected by infiltrative lymphocytic inflammation, which gradually leads to selective destruction and atrophy of the acinar tissue.Here, we analyzed the role of cell-mediated and humoral immune mechanisms in the pathogenesis of atrophic lymphocytic pancreatitis in German shepherd dogs and rough-coated collies. Pancreas biopsies and serum samples were obtained from 12 dogs with subclinical EPI (SEPI), 13 dogs with clinical EPI and 13 healthy control dogs. Immunohistochemical analysis showed that, in the subclinical phase, the majority of the infiltrating lymphocytes were T-cells with an almost equal number of CD4+ 'T-helper' and CD8+ 'cytotoxic' T-lymphocytes. The distribution of the two lymphocyte subsets was different. Typically, the CD4+ cells were present in large cellular infiltrates in the affected parenchyma, and the scattered CD8+ cells had infiltrated both the affected and the normal parenchyma. In sections where destruction of acinar parenchyma was present, the CD8+ T-cells were predominant. In cases of marked T-cell infiltration, CD79+ B-lymphocytes and plasma cells, and lysozyme-positive macrophages were also detected. Lymphoid follicle germinal centers with a majority of cells staining positively for CD79 were found. The lymphocytic infiltration in the totally atrophic tissue of dogs with clinical EPI was less prominent. Indirect immunofluorescence staining showed serum antibodies reacting weakly with pancreatic acinar cells in five out of nine dogs with subclinical and three out of 10 dogs with clinical EPI, but not in the control dogs. The results suggest that the tissue destruction is largely T-cell-mediated, although the presence of numerous B-lymphocytes and pancreas-specific antibodies in the sera of some dogs indicate that humoral mechanisms are also involved. In conclusion, this study suggests that the atrophic lymphocytic pancreatitis in German shepherds and rough-coated collies is an autoimmune disease.
Assuntos
Doenças do Cão/imunologia , Pancreatite/veterinária , Animais , Formação de Anticorpos , Antígenos CD/análise , Autoanticorpos/sangue , Eletroforese das Proteínas Sanguíneas/veterinária , Linfócitos T CD4-Positivos/imunologia , Antígenos CD79 , Linfócitos T CD8-Positivos/imunologia , Cães , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Imunidade Celular , Imunofenotipagem/veterinária , Masculino , Microscopia de Fluorescência/veterinária , Pancreatite/imunologia , Receptores de Antígenos de Linfócitos B/análiseRESUMO
Previously published studies of the pathology of canine exocrine pancreatic insufficiency (EPI) have been based on morphological findings during the clinical phase of the disease, when atrophy of acinar parenchyma occurs. Recently, low serum trypsinlike immunoreactivity (TLI) concentration has been shown to precede clinical signs, making it possible to diagnose EPI prior to onset of the clinical disease. This study presents histological and ultrastructural findings of pancreatic biopsies from 11 German Shepherd Dogs and 2 Rough-coated Collies with subclinical EPI (SEPI). These findings were compared with those from dogs with clinical EPI (n = 11) and healthy control dogs (n = 5). Biopsied tissue from dogs with SEPI typically contained both normal and atrophied acinar parenchyma. The most significant finding was the marked lymphocytic infiltration, which was most prevalent at the border zone of affected and nonaffected parenchyma but had spread into the normal acinar tissue. Numerous intraacinar lymphocytes were found. Most of the lymphocytes were positive by immunostaining for CD3. In more advanced stages of destruction, the findings were characteristic of pancreatic acinar atrophy. In the atrophied parenchyma, the inflammatory reaction, if present, was less prominent. Ultrastructural changes were in accordance with those of the histological study showing infiltration of lymphocytes both in affected acini and in acini that revealed no obvious ultrastructural changes. Progressive degenerative changes of acinar cells were considered a nonspecific finding. Apoptotic death of acinar cells was occasionally found. The inflammatory reaction was clearly shown to precede the pancreatic acinar atrophy, and the findings suggested that lymphocytic pancreatitis leads to atrophy of the pancreas. The possibility that EPI is an immune-mediated disease in German Shepherd Dogs and Rough-coated Collies is discussed.
Assuntos
Doenças do Cão/patologia , Pâncreas/patologia , Pancreatite/veterinária , Animais , Atrofia/patologia , Atrofia/veterinária , Biópsia/veterinária , Doenças do Cão/imunologia , Cães , Feminino , Imuno-Histoquímica , Linfócitos/patologia , Masculino , Microscopia Eletrônica/veterinária , Pâncreas/ultraestrutura , Pancreatite/imunologia , Pancreatite/patologiaRESUMO
Dogs (n = 158) with serum trypsinlike immunoreactivity (TLI) concentrations < or = 5.0 microg/L were studied. The diagnosis of clinical exocrine pancreatic insufficiency (EPI) was made in 114 of 158 dogs based on TLI concentration < 2.5 microg/L and clinical signs typical of EPI (eg, polyphagia, voluminous feces, weight loss). In 44 of 158 dogs, a single TLI measurement and clinical signs were not diagnostic. In 9 of 44 dogs, TLI was < 2.5 microg/L, indicating EPI, but the gastrointestinal signs were atypical or the dogs were asymptomatic. In 35 of 44 dogs, TLI was 2.5-5.0 microg/L. All 44 dogs were retested for TLI within 1-27 months (mean, 11.9 months). In 20 of 44 dogs, the retested TLI was normal (> 5.0 microg/L). In 4 of 44 dogs with clinically diagnosed EPI, the retested TLI was < 2.5 microg/L. In the remaining 20 of 44 dogs, TLI was persistently < 5.0 microg/L (range, 1.0-4.9 microg/L; mean, 3.1 microg/L). Of these dogs, 15 had no clinical signs of gastrointestinal disease, and 5 had occasional clinical signs atypical for EPI. Gross examination of the pancreas (12 dogs) showed that the amount of normal pancreatic tissue was remarkably diminished. These dogs were diagnosed with subclinical EPI. The TLI-stimulation test, in which TLI is measured before and after stimulation with secretin and cholecystokinin, showed a significant response (P < .05) both in dogs with subclinical EPI and in control dogs, but showed no response in dogs with clinical EPI. In this study, EPI was diagnosed in its subclinical phase by TLI concentrations persistently < 5.0 microg/L, and a single TLI concentration < 5.0 microg/L was not diagnostic. Retesting after TLI concentrations < 5.0 microg/L is recommended even in clinically normal dogs, because of the possibility of subclinical EPI.
Assuntos
Doenças do Cão/diagnóstico , Insuficiência Pancreática Exócrina/veterinária , Tripsina/sangue , Tripsinogênio/sangue , Animais , Diagnóstico Diferencial , Doenças do Cão/sangue , Cães , Insuficiência Pancreática Exócrina/sangue , Insuficiência Pancreática Exócrina/diagnóstico , Feminino , Masculino , Valor Preditivo dos Testes , Radioimunoensaio/veterináriaRESUMO
OBJECTIVE: To study response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency (EPI). DESIGN: Cross-sectional study. ANIMALS: 76 German Shepherd Dogs or rough-coated Collies with EPI and 145 clinically normal dogs of the same breeds. PROCEDURE: Questionnaires were sent to owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had been given dietary enzyme supplements for at least 4 months. Relative frequency distributions of gastrointestinal tract and dermatologic signs, prevalences of typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy feces, high fecal volume), feeding regimens, and dietary intolerances were compared between dogs with EPI and clinically normal dogs. RESULTS: Gastrointestinal tract signs considered typical for dogs with EPI were almost completely controlled with dietary enzyme supplements in half of the dogs with EPI, and their general health was similar to that of clinically normal dogs. A poor treatment response was found in a fifth of dogs with EPI that had several signs that were typical of EPI. Signs most often persisting were high fecal volume, yellow and pulpy feces, and flatulence. Dermatologic problems were common, especially in German Shepherd Dogs with EPI. Treatment response was irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and raw chopped pancreas were equally effective in controlling clinical signs. Although dietary sensitivities were common, use of adjunctive dietary treatment was minimal. Antibiotics were occasionally administered to half of the dogs with EPI. CLINICAL IMPLICATIONS: Results of this study indicate that, with basically similar treatment regimens, response to long-term enzyme treatment in dogs with EPI varied considerably.
Assuntos
Doenças do Cão/tratamento farmacológico , Terapia Enzimática , Insuficiência Pancreática Exócrina/veterinária , Pâncreas/enzimologia , Animais , Bovinos , Estudos Transversais , Dieta/veterinária , Suplementos Nutricionais , Doenças do Cão/dietoterapia , Cães , Enzimas/administração & dosagem , Insuficiência Pancreática Exócrina/dietoterapia , Insuficiência Pancreática Exócrina/tratamento farmacológico , Feminino , Masculino , Extratos Pancreáticos/administração & dosagem , Extratos Pancreáticos/uso terapêutico , Pós , Rena , Ovinos , Inquéritos e Questionários , SuínosRESUMO
The main objective of the study reported here was to determine whether signs typical of exocrine pancreatic insufficiency (EPI) are alleviated when affected dogs are fed a diet with low fat content, compared with feeding ordinary commercial dog food or food prepared by the owner. The most cost-effective amount of enzyme supplement also was estimated. The study consisted of 6 test periods. Duration of the first and third periods was 4 weeks, and that of the others was 2 weeks. During the first 2 periods, the dogs were fed their original diet. The amount of enzyme supplement was reduced by half between the first and the second period. During the last 4 periods, the dogs were fed only the low-fat diet, and amount of the enzyme supplement was reduced stepwise. During the entire study, owners were asked to assess daily the severity of 9 signs typical of EPI. A new index was established by adding the daily scores of each individual EPI sign. This index was designated the EPI index and was used as a measure of the general well-being of the dog. When the mean EPI indexes of the original diet periods were compared with those of the corresponding low-fat diet periods, there were no statistically significant differences by use of Tukey's test or the paired t-test. There was considerable variability between dogs, however. The fat content of the original diet did not correlate with the difference in EPI signs when the dogs were fed the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)