Pancreatitis in Dogs and Cats

PANCREATITIS in Dogs and Cats

an overview

PSA-DVM Paola Moreno Estanol

OVERVIEW

Pancreatitis, a multifaceted pancreatic inflammation, is increasingly recognized in veterinary practice. This article provides a comprehensive overview of its clinical presentation, diagnostics, treatment, and prognosis in dogs and cats, underscoring species-specific distinctions.

Clinical Presentation:

In dogs, pancreatitis spans from asymptomatic to severe systemic disease. Common symptoms include vomiting, abdominal pain, and dehydration. Chronic cases might manifest subtly, with anorexia or behavioral changes. Cats often exhibit nonspecific symptoms like lethargy, reduced appetite, and dehydration, with abdominal pain being less overt.

Diagnosis:

Diagnosis relies on a combination of clinical assessment, laboratory tests, and imaging. Blood tests, particularly serum cPLI in dogs and fPLI in cats, are critical. However, these tests have limitations in sensitivity, necessitating comprehensive diagnostic approaches. Abdominal ultrasound is the primary imaging modality, revealing pancreatic alterations and adjacent abnormalities. Radiography offers less specificity but is useful in excluding differential diagnoses. Advanced imaging techniques like CT and MRI provide detailed insights but are less commonly employed.

Treatment:

Acute Pancreatitis: Aggressive supportive care is imperative, encompassing fluid therapy, analgesia, and antiemetic treatment. Nutritional support is essential, with dogs benefitting from a low-fat diet, while cats require high-protein, moderate-fat diets.

Chronic Pancreatitis: 

Management focuses on dietary modification and pain control. In dogs, anti-inflammatory drugs, including corticosteroids, are used with caution. In cats, immunomodulatory therapies are often effective.

Prognosis:

The prognosis is contingent on disease severity, systemic complications, and concurrent conditions. Chronic pancreatitis in dogs can lead to diabetes and exocrine pancreatic insufficiency. In cats, it often occurs as part of multi-organ inflammatory syndrome.

Conclusion:

Understanding the nuances of pancreatitis in dogs and cats is crucial for effective management. This comprehensive overview synthesizes current knowledge, offering a foundation for evidence-based clinical decision-making in veterinary medicine.

Introduction:

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Pancreatitis in dogs and cats is a multifaceted condition, manifesting in both acute (AP) and chronic (CP) forms, posing significant diagnostic complexities. The clinical symptoms often mimic those of other non-pancreatic diseases and differ between the acute and chronic stages. Diagnosing pancreatitis is challenging due to inconsistent results from laboratory tests and abdominal ultrasound. Although morphological differentiation of pancreatic inflammation through ultrasound-guided fine-needle aspiration or biopsy is possible, it's infrequently practiced. The origins of pancreatitis are largely unknown, but several risk factors, including breed predispositions, genetic factors, hypertriglyceridemia, obesity, dietary errors, and certain infections, are suggested. The disease's pathophysiology encompasses acinar cell destruction and systemic inflammatory responses, leading to a spectrum of conditions ranging from mild AP to severe necrotizing pancreatitis with systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Understanding the risk factors, pathophysiology, and clinical variations of AP and CP is essential for effective treatment and management in veterinary medicine. The prevalence of pancreatitis is notable, with necropsy studies indicating a significant incidence in dogs. While chronic pancreatitis often goes undiagnosed, it can lead to grave complications such as diabetes mellitus and exocrine pancreatic insufficiency. In cats, previously underdiagnosed pancreatitis is now acknowledged as a common exocrine pancreatic disorder, thanks to advances in diagnostic modalities and a deeper understanding of its unique clinical presentations.

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Pathophysiology:

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The pathophysiology of pancreatitis in dogs and cats is intricate, stemming from the premature activation of pancreatic enzymes, notably trypsin, within the pancreatic acinar cells. Normally inactive until reaching the small intestine, trypsinogen's early conversion into trypsin within the pancreas triggers inflammation and obstruction, exacerbated by genetic factors. This activation ignites a chain reaction, activating other enzymes like chymotrypsin and elastase, leading to pancreatic tissue autodigestion. The resulting damage releases pro-inflammatory cytokines and chemokines, intensifying the inflammation and sparking systemic effects, including pancreatic necrosis, hemorrhage, edema, multi-organ dysfunction, and sepsis.At the molecular level, pancreatitis engages multiple signaling pathways, particularly the NF-κB pathway, crucial in managing immune and inflammatory responses. Activated by stimuli such as cytokines and oxidative stress, NF-κB regulates genes linked to inflammation, cell survival, and apoptosis. Other pathways like MAPK and JAK/STAT also play significant roles in the disease's pathogenesis. Additionally, changes in intestinal microbiota, or dysbiosis, contribute to the inflammatory cascade, potentially leading to bacterial translocation to the pancreas and aggravating inflammation.

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Clinical Presentation:

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The clinical manifestation of pancreatitis in canines varies, ranging from asymptomatic chronic forms to severe acute expressions. Acute episodes typically present with emesis, pronounced abdominal discomfort, lethargy, and dehydration, occasionally accompanied by diarrhea and pyrexia. Systemic complications may exhibit as oliguria or anuria in renal impairment, respiratory distress due to pulmonary involvement, neurological manifestations in pancreatic encephalopathy, and hemorrhagic phenomena in disseminated intravascular coagulation. Chronic conditions are often subtle, characterized by diminished appetite, lethargy, and behavioral alterations.Feline presentations of pancreatitis are more elusive, commonly displaying anorexia, lethargy, dehydration, and emesis. Contrasting with canine cases, abdominal pain in felines is less evident, often under-recognized due to diagnostic intricacies. This indistinct presentation necessitates considering pancreatitis in differential diagnoses for felines presenting with vomiting, anorexia, or lethargy of unidentified origin. Distinguishing acute from chronic pancreatitis based on clinical signs is challenging in cats, with both forms potentially leading to critical complications or coexisting morbidities.

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Imaging Diagnosis:

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Clinical Imaging Diagnosis in Dogs with Pancreatitis:

Abdominal ultrasonography, the primary diagnostic imaging modality for canine pancreatitis, shows variable sensitivity based on factors like equipment quality, operator expertise, and disease severity. Severe acute pancreatitis in dogs may display pancreatic necrosis as hypoechoic areas within the pancreas. Other ultrasonographic signs include pancreatic enlargement, peritoneal effusion, and hyperechoic peripancreatic fat. However, specificity is limited due to similar ultrasonographic changes caused by other abdominal pathologies. For instance, abdominal effusion from different etiologies or pancreatic enlargement due to portal hypertension can mimic pancreatitis. Furthermore, pancreatic nodular hyperplasia, common in older dogs, might cause echogenicity changes, complicating diagnosis. Therefore, an experienced ultrasonographer's skill is critical for accurate interpretation. Historically, computed tomography (CT) and magnetic resonance imaging (MRI) were less favored due to perceived insensitivity in canine pancreatitis diagnosis.

Clinical Imaging Diagnosis in Cats with Pancreatitis:

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Plain radiographic changes in acute feline pancreatitis include reduced abdominal contrast, bowel loop dilation, and pleural effusion. However, these signs are subtle and non-specific with low sensitivity. Chronic pancreatitis in cats lacks well-characterized radiographic signs. The use of high-resolution abdominal ultrasonography has enhanced the diagnostic imaging of feline pancreatic diseases. Ultrasonographic findings consistent with pancreatitis in cats include pancreatic enlargement, altered parenchymal echogenicity, abdominal effusions, and pancreatic duct dilation. Despite these specific indicators, ultrasound sensitivity varies greatly, and it cannot be solely relied upon for definitive diagnosis. Endoscopic ultrasonography, although feasible in cats, has not significantly altered diagnoses compared to traditional methods. CT scans in cats with pancreatitis have shown low sensitivity and no appreciable difference in pancreatic appearance between normal and symptomatic cats. Considering the cost and need for sedation or anesthesia, CT is generally not recommended for diagnosing feline pancreatitis. Thus, abdominal ultrasonography, performed by skilled operators, remains crucial in evaluating suspected pancreatitis in cats, especially for identifying comorbid conditions.

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Pathology Diagnosis:

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Pathology Diagnosis in Dogs with Pancreatitis:

In dogs, a variety of hematological and serum biochemical changes are observed in acute severe pancreatitis, reflecting systemic conditions rather than direct pancreatic inflammation. Hematological and serum chemistry profiles aid in excluding alternative diagnoses. Serum Amylase Activity, a hydrolytic enzyme for complex carbohydrates, is inconsistently elevated in canine pancreatitis, rendering it a less reliable marker. Total Serum Lipase Activity, which hydrolyzes triglycerides, shows limited specificity and sensitivity for canine pancreatitis. The synthetic substrate resorufin (DGGR) offers improved utility but is not exclusively specific for pancreatic inflammation.

Pancreatic Lipase Immunoreactivity (PLI), particularly canine PLI (cPLI), is a specific assay for pancreatic lipase and serves as the most sensitive diagnostic tool for canine pancreatitis. Serum cPLI has demonstrated high specificity and sensitivity in various clinical studies. Trypsin-like Immunoreactivity (TLI) is specific to exocrine pancreatic function but has lower sensitivity for pancreatitis compared to PLI or ultrasound. However, TLI remains the choice for diagnosing Exocrine Pancreatic Insufficiency (EPI).

For cytology, fine-needle aspirates of the pancreas can confirm pancreatic inflammation, but severe necrosis may yield inconclusive results. Histopathologic evaluation via biopsy, though definitive, may miss localized lesions in mild chronic pancreatitis. Surgical risks in severe cases also limit its use.

Pathology Diagnosis in Cats with Pancreatitis:

Routine biochemistry and Complete Blood Count in cats reveal common abnormalities like leukocytosis, elevated liver enzymes, and electrolyte imbalances, but no specific pattern is indicative of pancreatitis. The lack of specificity in traditional amylase and lipase activities necessitates pancreas-specific diagnostic tests.

Feline Trypsin-Like Immunoreactivity (fTLI) and Pancreatic Lipase Immunoreactivity (fPLI/Spec fPL) have been explored for their diagnostic potential. While fTLI offers limited sensitivity, fPLI/Spec fPL shows higher sensitivity and specificity for pancreatitis. However, fTLI's specificity is questioned due to elevated levels in other significant diseases.

DGGR-lipase assay, a substrate with high specificity for pancreatic lipases, presents a promising alternative, showing moderate to substantial agreement with Spec fPL in diagnosing pancreatitis. However, DGGR-lipase's clinical utility is still under investigation.

Pancreatic biopsy via laparoscopic techniques, considered the gold standard, often yields useful information. Chronic pancreatitis is the most common histological finding in feline patients. The procedure's invasiveness, potential for post-surgical complications, and the patchy distribution of lesions pose challenges in feline pancreatic biopsy, suggesting the need for multiple samples for accurate diagnosis. Despite these limitations, pancreatic biopsy is increasingly recognized as a valuable diagnostic tool in feline pancreatitis, provided it is performed judiciously.

Histopathological examination remains the definitive method for diagnosing pancreatitis in cats, distinguishing between acute and chronic forms based on inflammatory patterns. Acute pancreatitis is characterized by interstitial edema, neutrophilic infiltration, and potential mesenteric fat necrosis. Chronic pancreatitis, more common in felines, exhibits lymphocytic infiltration, fibrosis, and cystic acinar degeneration. Histological findings often reveal a mixed pattern of inflammation with patchy lesion distribution. Necropsy studies indicate high prevalence, with chronic inflammation noted in 60% of cases, and a mix of acute and chronic changes in others. Pancreatic biopsies frequently reveal chronic or acute-on-chronic pancreatitis, underscoring its prevalence in clinical suspicions of feline pancreatic disease.

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Treatment of Acute Severe Pancreatitis in Dogs:

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Treatment of Cause:

Identifying and treating the cause of pancreatitis is crucial, although most cases in dogs are idiopathic. Dietary indiscretion and severe hypertriglyceridemia are notable risk factors. In Miniature Schnauzers, SPINK-1 gene mutations are linked to the disease. Other potential causes include blunt external trauma, surgical trauma, hypoperfusion during anesthesia, and certain infections like Babesia canis and Leishmania infantis. A thorough history, including trauma, dietary indiscretion, and drug exposure, is essential. Blood tests, including triglycerides and calcium levels, can provide etiological clues.

Supportive Care:

Aggressive fluid therapy is essential for dogs with severe pancreatitis to correct fluid, electrolyte, and acid-base imbalances. Systemic complications associated with worse outcomes require early intervention. Nutritional support is crucial; enteral nutrition is preferable to parenteral. If oral feeding is not possible, feeding tubes (gastrostomy, esophagostomy, or nasogastric) should be used. For persistent vomiting, jejunostomy or parenteral nutrition may be necessary.

Analgesia:

Abdominal pain, a common symptom in pancreatitis, may be underappreciated in dogs. Analgesic drugs like meperidine, butorphanol, buprenorphine, morphine, fentanyl, and methadone are recommended, assuming pain presence in all dogs with pancreatitis.

Antiemetics:

Antiemetics are critical for managing nausea and vomiting, which can impede nutritional support. Maropitant is preferred, with ondansetron as an additional option for refractory cases. Metoclopramide is generally insufficient for severe cases.

Proteinase Inhibitors:

Despite theoretical benefits in managing pancreatitis, proteinase inhibitors have not shown significant efficacy in dogs with spontaneous pancreatitis, unlike in experimental settings.

Fresh Frozen Plasma:

The use of fresh frozen plasma in severe pancreatitis is debated. While it contains useful proteins and factors, its efficacy in improving outcomes is not definitively proven and may be associated with worse outcomes in some studies.Antibiotics:Routine antibiotic use is not recommended unless a bacterial infectious complication is confirmed or strongly suspected, as bacterial infections are less common in canine pancreatitis compared to humans.

Anti-inflammatory Agents:

Glucocorticoids and non-steroidal anti-inflammatory drugs have not shown benefits in pancreatitis and should be used cautiously, mainly in cases with cardiovascular shock.

Other Therapeutic Strategies:

Various experimental treatments, including antioxidants, probiotics, antacids, antisecretory agents, and PAF inhibitors, have not consistently demonstrated benefits in canine pancreatitis. Dopamine may be beneficial during anesthesia but is not effective in routine therapy.

Surgical Intervention:

Conservative management is generally preferred in canine pancreatitis. Surgical intervention is limited to specific cases like infected necrosis or fluid accumulations. Secondary biliary obstruction rarely necessitates surgery and may worsen the patient's condition.

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Therapeutic Approach to Pancreatitis in Cats

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Management of Severe Disease:Cats presenting with severe pancreatitis require immediate, aggressive hospital-based care. Treatment includes:Fluid Therapy:

Administering synthetic colloid and crystalloid fluids is crucial for resuscitation and maintaining volume. Fresh-frozen feline plasma may provide oncotic support and replenish coagulation proteins, although its use in severe cases is not well-documented.Electrolyte Management:

Addressing substantial electrolyte abnormalities, especially hypokalemia and hypocalcemia, is essential. Potassium supplementation should be tailored based on serum levels.Analgesia and Antiemetic Therapy:

Narcotic pain control, such as transdermal fentanyl patches and sublingual buprenorphine, is necessary. Additionally, maropitant, a neurokinase-1 receptor antagonist, provides effective antiemetic and antinociceptive effects. Combining it with a 5-HT3-receptor antagonist, like ondansetron or dolasetron, effectively controls vomiting and nausea.Nutritional Support:

Early reintroduction of feeding is generally well tolerated and beneficial. Enteral nutrition is associated with better outcomes and fewer side effects.Comorbidity Management:

Screening and appropriate treatment for comorbidities, such as hepatic disease and diabetes mellitus, are vital.

Management of Chronic Pancreatitis in Cats:

Cats with chronic pancreatitis are treated similarly to those with chronic enteropathies or idiopathic inflammatory bowel disease:Dietary Modification:

Implementing a novel protein source or hypoallergenic diet is recommended. Unlike dogs, fat restriction is not advised in cats due to their high dietary fat requirement.Anti-inflammatory Therapy:

If dietary modification is ineffective, considering anti-inflammatory or immune-modulatory therapies is rational, provided there are no contraindications due to other comorbidities.Overall, the management of pancreatitis in cats, whether acute or chronic, involves a multifaceted approach encompassing fluid therapy, electrolyte management, pain control, antiemetic therapy, nutritional support, and addressing comorbid conditions. Careful monitoring and adjustment of treatment plans are crucial based on the individual cat's response and evolving clinical picture.

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Treatment of Mild Chronic Pancreatitis in Dogs:

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In managing mild chronic pancreatitis in dogs, a multifaceted approach is necessaryTreatment of Cause:

Identifying and addressing underlying causes is crucial. Assess for hypertriglyceridemia, hypercalcemia, and drug history. Concurrent conditions like idiopathic inflammatory bowel disease, chronic hepatitis, and diabetes mellitus should be evaluated through serum analyses (glucose, cobalamin, folate, hepatic enzymes) and further diagnostics if abnormalities are detected.Antiemetic and Analgesic Therapy:

Tailor therapy based on clinical signs. Mild analgesics like butorphanol or tramadol are used for discomfort without overt pain. Fentanyl patches are recommended for significant abdominal pain. Antiemetic therapy, involving maropitant and/or a 5-HT-antagonist, is necessary for symptoms like vomiting, hyporexia, or anorexia.Dietary Management:

Switching to an ultra-low-fat diet (<20 g fat/1,000 kcal) is essential. Educate owners about low-fat treats, considering vegetables, fruits, or home-made treats. In cases with concurrent conditions like food hypersensitivity or chronic kidney disease, dietary requirements for pancreatitis take precedence, or a custom diet may be formulated with a veterinary nutritionist's assistance.Monitoring and Adjusting Treatment:

Regular rechecks (every 2-3 weeks initially) are vital to monitor clinical signs and serum Spec cPL concentrations. Adjust the frequency of rechecks as the condition stabilizes.Exploratory Therapies:

In refractory cases, corticosteroids (prednisone protocol) and cyclosporine have shown some promise. While anecdotal success and ongoing clinical trials suggest potential benefits, further studies are needed before widespread recommendation.The treatment of mild chronic pancreatitis in dogs requires a comprehensive and individualized approach, focusing on addressing underlying causes, managing symptoms, dietary adjustments, and regular monitoring. Exploratory treatments like corticosteroids and cyclosporine may be beneficial in some cases but require further validation.

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Prognosis:

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The prognosis for pancreatitis in dogs hinges on factors like disease severity, pancreatic necrosis extent, systemic and pancreatic complications, disease duration, and concurrent illnesses. While several prognostic systems from human medicine have been adapted for canine use, their effectiveness in routine clinical settings remains unproven. These systems aim to identify high-risk patients for aggressive treatment, but their utility in predicting outcomes in dogs with pancreatitis has not been established with certainty.

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References:

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• Ettinger SJ. Textbook of Veterinary Internal Medicine. 8th ed. ELSEVIER. 2017.

• Forman, MA. ACVIM consensus statement on pancreatitis in cats. J Vet Intern Med. 2021;35:703–723.

• Cridge, H. Advances in the Diagnosis of Acute Pancreatitis in Dogs. J Vet Intern Med. 2021 Nov:35(6):2572-2587.

• Cridge, H. New Insights into the Etiology, Risk Factors, and Pathogenesis of Pancreatitis in Dogs. J Vet Intern Med. 2022 May;36(3):847-864.

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