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Feline Exocrine Pancreatic Disease (VET-192)

WESTERNVETERINARYCONFERENCE2004

Robert J. Washabau, VMD, PhD, DACVIMSchool of Veterinary Medicine, University of Pennsylvania

Philadelphia, PA, USA

HISTOLOGICCLASSIFICATIONOFFELINEPANCREATICLESIONS

Based on a recent retrospective review of our pathology database, we have developed a revised classification scheme for feline exocrine pancreatic pathology, which is characterized in thefollowing way:

Acute necrotizing pancreatitis--Peri-pancreatic fat necrosis and/or pancreatic acinar cell necrosis (>50% of the pathology), inflammation, hemorrhage, mineralization, fibrosis. Inflammation can be present, but necrosis must be the predominant feature.

Acute suppurative pancreatitis--Neutrophilic (>50%) pancreatic inflammation necrosis. Necrosis can be present, but PMN's must be the predominant feature.

Chronic non-suppurative pancreatitis--Lymphocytic/plasmacytic inflammation, fibrosis, acinar atrophy. Necrosis and suppuration can be present in small amounts, butlymphocytes must be the predominant feature.

Pancreatic nodular hyperplasia--Nodules of pancreatic acinar and/or ductular tissue are present. Fibrosis is not a feature of this condition.

Pancreatic neoplasia--Malignancy of pancreatic origin, whether accompanied by necrosis, inflammation, fibrosis, hemorrhage, or mineralization.

Pancreatic pseudocyst/abscess--Cystic structure observed at ultrasound and/or surgery and/or necropsy. Cystic cavity contains fluid, pancreatic cells, enzyme.

Pancreatic atrophy--Hypoplasia, degeneration, involution, or apoptosis of the exocrine portion of the gland. The endocrine portion of the gland may be spared or involved in thesame process.

FELINEACUTENECROTIZINGPANCREATITIS

Introduction--Peripancreatic fat necrosis and acinar cell necrosis are now recognized as an important cause of morbidity and mortality in the domestic cat. Reports of this condition wereuncommon prior to the early 1990's, probably related to diffi culties in diagnosis as well as low incidence of disease. Some of the difficulties in the diagnosis and treatment of this disordermay have, in fact, related to preconceived notions about the same disorder in the dog. Like many other companion animal disorders, there are important differences in the natural historyof the disease between cats and dogs.

History--Siamese cats were reported to be at increased risk for the disease in the first retrospective study of feline pancreatitis. A more recent study suggests that most cases ofpancreatitis are seen in the Domestic Short Hair breed. Lethargy (100%) and partial to complete anorexia (97%) are the most frequently reported clinical signs in cats with acute

pancreatitis, but, of course, these clinical signs are not pathognomonic for pancreatitis. Lethargy and anorexia are the most important clinical signs in many feline diseases.Gastroenterologic signs are sporadic and less frequently reported. For example, vomiting (35%) and diarrhea (15%) were less frequently reported clinical signs in a retrospective study of40 cases of feline acute pancreatitis. Similar findings were reported in a more recent study of feline pancreatitis. In canine acute pancreatitis, vomiting (90%) and diarrhea (33%) appear

to be more important clinical signs.

Physical Examination Findings--Physical examination findings in cats with acute pancreatitis include dehydration (92%), tachypnea (74%), hypothermia (68%), icterus (64%),tachycardia (48%), abdominal pain (25%), abdominal mass (23%), dyspnea (20%), ataxia (15%), and fever (7%). These findings clearly suggest that a "textbook" description of acute

pancreatitis (e.g., vomiting, diarrhea, abdominal pain, and fever) is uncommonly seen in the domestic cat. Many of these physical examination findings are more commonly reported incanine acute pancreatitis. For example, abdominal pain (58% in dogs; 25% in cats) and fever (32% in dogs; 7% in cats) are more commonly reported in dogs with acute pancreatitis.

Laboratory Findings--In 40 cats with spontaneous acute pancreatitis, laboratory abnormalities included: normocytic, normochromic regenerative anemia (55%), leukocytosis (30%),

leukopenia (15%), hyperglycemia (64%), azotemia (57%), hypocalcemia (45%), hypokalemia (56%), hypoalbuminemia (24%), hyperbilirubinemia (64%), hypercholesterolemia (64%),and elevations in serum alanine aminotransferase (68%) and alkaline phosphatase (50%) activities. Similar changes were reported in a more recent retrospective review of feline acutepancreatitis. Thus, changes in red and white blood cell counts, serum activities of liver enzymes, and serum concentrations of bilirubin, glucose, and cholesterol are fairly consistent

findings in spontaneous feline acute pancreatitis, just as they are in the canine disorder. Important differences between cats and dogs appear to be reflected in white blood cell counts andserum calcium concentrations. Leukocytosis is a more important clinical finding in the dog (62% in dogs; 30% in cats). Leukopenia is sometimes seen instead of leukocytosis in cats, and aworse prognosis has been attributed to leukopenia in the cat. Hypocalcemia also appears to be a more frequent finding in cats (3-5 % in dogs; 45-50% in cats. Hypocalcemia (total andserum ionized) may result from several mechanisms, e.g., acid-base disturbances, peripancreatic fat saponification, and/or parathormone resistance. Regardless of the mechanism,

hypocalcemia appears to confer a worse clinical prognosis in cats-greater morbidity and mortality were reported in association with hypocalcemia in a recent retrospective report of felineacute pancreatitis. This finding suggests that cats should be monitored fairly closely for the development of hypocalcemia. Serum trypsinogen-like immunoreactivity (TLI) concentrationsappear to be elevated early in feline acute pancreatitis, but some peaks may be missed during the clinical evolution of the disease. Serum amylase and lipase activities do not appear to beuseful in the diagnosis of feline acute pancreatitis, whereas these enzyme activities may still have some clinical utility in the diagnosis of canine acute pancreatitis. Assays of the

trypsinogen activation peptide (asp-asp-asp-asp-lys) appeared to have some promise based on experimental studies, but more recent studies have not shown consistent clinical results.

Feline pancreatic-specific lipase assays (fPLI) may hold some additional benefit over feline TLI (fTLI). Indeed, fPLI may be more sensitive and specific than fTLI.Imaging Findings--The radiographic findings of acute pancreatitis in the domestic cat have not been very well characterized. It has been suggested that the radiographic findings of

acute pancreatitis in the dog (e.g., increased density in the right cranial abdominal quadrant, left gastric displacement, right duodenal displacement, and gas-filled duodenum/colon) are

similar in the cat. This statement has not been very well substantiated. Indeed, in several recent reports, many of these radiographic findings were not reported in cats with documentedacute pancreatic necrosis. In spontaneous clinical cases, hepatomegaly and abdominal effusion are the most common radiographic findings. Hypoechoic pancreas, hyperechogenicity of theperipancreatic mesentery, and peritoneal effusion have been observed with abdominal ultrasonography in many cats with spontaneous acute pancreatitis. The sensitiv ity and specificity of

this imaging modality have not yet been determined. Recent studies suggest a high sensitivity (>85%) but a low sensitivity (

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secretion is no longer present. Although this process takes place in other cells without adverse consequences, it can be lethal in pancreatic acinar cells because of the peculiarity of their

secretion products (digestive zymogens). Lysosomal hydrolases, such as cathepsin B and N-acetyl glucosaminidase, activate trypsinogen to the active trypsin form, and the enhancedfragility of these large vacuoles permits release of active enzyme into the cell cytoplasm. Trypsin acts auto-catalytically to activate other trypsinogen molecules and other zymogens, eachinducing a unique chemical pathology in pancreatic and extra-pancreatic cells. A variety of inflammatory mediators and cytokines (tumor necrosis factor-, interferon-, interferon-,platelet-activating factor), interleukins (IL-1, IL-2, IL-6, IL-8, IL-10), nitric oxide, and free radicals are involved in the further evolution of pancreatic acinar cell necrosis and inflammation.

Therapy--Supportive care continues to be the mainstay of therapy for feline acute pancreatitis. Thus, efforts should be made to identify and eliminate any inciting agents, sustain bloodand plasma volume, correct acid/base and electrolyte disorders, place the pancreas in physiologic rest (NPO) for short periods of time, and treat any complications that might develop.Important complications of acute pancreatitis in cats include hypocalcemia, disseminated intravascular coagulation, thromboembolism, cardiac arrhythmia, sepsis, acute tubular necrosis,pulmonary edema and pleural effusion. Other therapies of benefit in the treatment of this disease include relief of pain (fentanyl, buprenorphine), anti-emetic agents (2adrenergic

antagonists, 5-HT3antagonists), calcium gluconate supplementation, H2histamine antagonists (to improve pancreatic blood flow), low dose dopamine infusion (5 g/kg/min; to improve

pancreatic blood flow), and broad spectrum antibiotics (to reduce colonic bacterial translocation). High colonization rates suggest that bacteria may spread to the inf lamed pancreas more

frequently than is currently thought, and that broad-spectrum antibiotics may be appropriate in suspected cases of feline acute pancreatitis.

CHRONICNON-SUPPURATIVEPANCREATITIS

Results of a recent study in our Hospital suggest that ante mortem differentiation of acute and chronic pancreatitis cannot be made based solely on clinical, clinicopathologic, or imagingfindings. Many of the clinical criteria that clinicians have attributed to acute pancreatitis may also be seen in cats with histologically confirmed chronic pancreatitis. The prevalence of

concurrent disease in both groups described in this s tudy makes it difficult to determine if the nonspecific findings in history, physical examination, clinicopathologic and radiographicfindings are attributable to acute or chronic pancreatitis. Although the absence of concurrent disease may suggest presentation with acute pancreatitis, histopathology remains the onlydependable method of differentiating acute and chronic pancreatitis. In addition, the clinical relevance of differentiating acute and chronic pancreatitis with regard to morbidity, mortality,and outcome, requires further evaluation.

EXOCRINEPANCREATICINSUFFICIENCY

Exocrine pancreatic insufficiency (EPI) is an uncommon cause of chronic diarrhea in cats. Insufficiency results from failure of synthesis and secretion of pancreatic digestive enzymes. Thenatural history of feline exocrine pancreatic insuff iciency is poorly understood, but many cases are thought to result from chronic pancreatitis. As with dogs, clinical signs reported in cats

with EPI include weight loss, soft voluminous feces, and greasy soiling of the hair coat. Affected cats may also have an antecedent history of recurring bouts of acute pancreatitis (e.g.,anorexia, lethargy, vomiting) culminating in chronic pancreatitis and EPI.

The diagnosis of EPI in cats has been technically difficult. Clinical signs in affected cats are not pathognomonic for EPI, clinicopathologic data are fairly non-specific, imaging findings areinconsistent, and the severity of pancreatic histologic changes are not always directly related to the severity of clinical signs. A feline-specific radioimmunoassay for trypsin-likeimmunoreactivity (TLI) has been developed, and a recent paper suggests that it may prove useful in the diagnosis of this disease. In that study, TLI concentrations less than 8 g/L

(reference range = 17-49 g/L) were reported in 17/20 cats with clinical signs compatible with EPI (e.g., weight loss, loose voluminous feces, greasy soiling of the hair coat) and at leastone other finding, e.g., decreased fecal proteolytic activity, exploratory laparotomy or necropsy findings compatible with EPI, or favorable response to pancreatic enzyme replacementtherapy.

References

References are available upon request.

SPEAKERINFORMATION(click the speaker's name to view other papers and abstracts submitted by this speaker)

Robert J . Washabau, VMD, PhD, DACVIM

Professor of MedicineUniv. of PA, School of Veterinary MedicinePhiladelphia, PA

Front Page: Library: WVC 2004: Small Animal: Gastroenterology: Exocrine Pancreatic Disease

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