Etiology and Pathogenesis
Most cases of pancreatitis in dogs and cats are idiopathic. However, several risk factors have been identified. Miniature Schnauzers have been reported to be dramatically overrepresented in some studies, and it has been speculated that they may have a genetic predisposition similar to that in families of human patients with hereditary pancreatitis. Other studies have reported an increased prevalence in Yorkshire Terriers, Cocker Spaniels, Dachshunds, Poodles, sled dogs, or other breeds.
Dietary indiscretion is believed to be a common risk factor in dogs. Also, hypertriglyceridemia, if severe (ie, generally serum concentrations ≥500 mg/dL), is considered a risk factor for pancreatitis in dogs but not in cats. Hyperadrenocorticism Cushing Syndrome (Hyperadrenocorticism) Cushing syndrome refers to any cause of elevated cortisol concentrations. Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) is the most common form of hyperadrenocorticism and... read more has been cited in some studies as a risk factor for pancreatitis in dogs. Severe blunt trauma, such as can be sustained during a traffic accident or in cats with high-rise syndrome, can also cause pancreatitis. Surgery has been considered another risk factor; however, most postsurgical cases of pancreatitis are now believed to be due to pancreatic hypoperfusion during anesthesia. Infectious diseases have been implicated, but the evidence for a cause and effect relationship is weak in most cases. In dogs, pancreatitis has been reported with Babesia canis Babesiosis Babesiosis is caused by intraerythrocytic protozoan parasites of the genus Babesia. Transmitted by ticks, babesiosis affects a wide range of domestic and wild animals and occasionally people... read more or Leishmania infection Leishmaniosis in Dogs The leishmaniases are spectral diseases caused by protozoan parasites of the genus Leishmania. Key signs range from localized cutaneous lesions to lymphadenopathy and renal failure for visceral... read more . In cats, Toxoplasma gondii Toxoplasmosis in Animals Toxoplasmosis is an important zoonotic protozoal infection worldwide. All homoeothermic animal species may be infected. Infection is generally asymptomatic and chronic in immunocompetent individuals... read more , Amphimerus pseudofelineus, and feline infectious peritonitis Overview of Feline Infectious Peritonitis Feline infectious peritonitis (FIP) is an immune-mediated disease triggered by infection with a feline coronavirus (FCoV). FCoV belongs to the family Coronaviridae, a group of enveloped, positive-stranded... read more are considered most important.
Many drugs have been implicated in causing pancreatitis in people, but very few have been confirmed in dogs and cats. In general, most drugs should be viewed as potential causes of pancreatitis; cholinesterase inhibitors, calcium, potassium bromide, phenobarbital, l-asparaginase, estrogen, salicylates, azathioprine, thiazide diuretics, and vinca alkaloids are probably the most important.
Many different insults may ultimately lead to pancreatitis through a common pathway. Secretion of pancreatic juice decreases during the initial stages of pancreatitis. This is followed by co-localization of zymogen granules and lysosomes, leading to activation of trypsinogen to trypsin within the co-localized organelles. Trypsin, in turn, activates more trypsinogen and also other zymogens. Prematurely activated digestive enzymes lead to local damage of the exocrine pancreas with pancreatic edema, bleeding, inflammation, necrosis, and peripancreatic fat necrosis. The ensuing inflammatory process leads to recruitment of WBCs and cytokine production. The activated enzymes, and more importantly, the cytokines circulate in the bloodstream and lead to distant complications such as generalized inflammation, disseminated intravascular coagulation, disseminated lipodystrophy, pancreatic encephalopathy, hypotension, renal failure, pulmonary failure, myocarditis, or even multiorgan failure.
In dogs with the most severe forms of pancreatitis (ie, the patients in one study all either died or were euthanized because of the severity of their disease), anorexia (91%), vomiting (90%), weakness (79%), abdominal pain (58%), dehydration (46%), and diarrhea (33%) have been reported as the most common clinical signs, but it is crucial to note that these findings don't reflect the clinical signs typically encountered in all patients with pancreatitis seen in a typical veterinary practice.
Clinical signs in cats with similarly severe forms of pancreatitis are even less specific, with anorexia (87%), lethargy (81%), dehydration (54%), weight loss (47%), hypothermia (46%), vomiting (46%), icterus (37%), fever (19%), and abdominal pain (19%) most commonly reported.
Dogs and cats with milder forms of pancreatitis may be subclinical or may have only vague clinical signs, such as anorexia, lethargy, or diarrhea.
The low rate of abdominal pain reported is remarkable given that >90% of human patients with pancreatitis report abdominal pain, so it is most likely due to lack of recognition Recognition and Assessment of Pain in Animals Pain is a complex, multidimensional experience with sensory and affective elements. All mammals process the neuroanatomic and neuropharmacologic components involved in transduction, transmission... read more in veterinary patients.
Integrating clinical findings, imaging findings, and results from measurement of serum pancreatic lipase immunoreactivity
A history of dietary indiscretion combined with vomiting and abdominal pain may suggest pancreatitis in dogs, but most cats present with nonspecific histories and clinical signs. Findings on CBCs and serum biochemistry profiles may suggest inflammation but are nonspecific. Changes on a CBC and chemistry profile mainly reflect systemic complications or concurrent disease and may also help to rule out other potential differential diagnoses.
Abdominal radiographs Diagnostic Imaging of Animals Radiography (generation of transmission planar images) is one of the most commonly used diagnostic tools in veterinary practice even though other imaging modalities such as ultrasonography,... read more may show decreased detail in the proximal abdominal cavity and displacement of abdominal organs, but these findings are also nonspecific and a diagnosis based on radiographic findings alone is unreliable. However, abdominal radiographs are valuable in animals suspected of having pancreatitis to exclude other differential diagnoses. Abdominal ultrasonography Ultrasonography in Animals Ultrasonography is the second most commonly used imaging format in veterinary practice. It uses ultrasonic sound waves in the frequency range of 1.5–15 megahertz (MHz) to create images of body... read more , if stringent criteria are applied, is fairly specific for severe forms of acute pancreatitis, but pancreatic enlargement and fluid accumulation around the pancreas alone are not sufficient for diagnosis. A combination of pancreatic enlargement, fluid accumulation around the pancreas, changes in echogenicity (ie, decreased echogenicity suggesting pancreatic necrosis, increased echogenicity around the pancreas suggesting peripancreatic fat necrosis), and/or a pancreatic mass effect are suggestive of pancreatitis.
Care should be taken not to overinterpret findings, because modern ultrasonographic equipment has a very high resolution, and pancreatic nodular hyperplasia may lead to changes in echogenicity, falsely suggesting the presence of pancreatitis. Also, the sensitivity of abdominal ultrasonography is highly operator-dependent, with sensitivities as high as 35% in cats and 68% in dogs in the most experienced hands.
More advanced imaging techniques such as contrast-enhanced ultrasonography, computed tomography Computed Tomography in Animals In computed tomography (CT), an x-ray tube moves around the body and continuously projects a thin fan of x-rays through the body. Electronic detectors opposite the tube continuously monitor... read more , or magnetic resonance imaging Magnetic Resonance Imaging in Animals Magnetic resonance imaging (MRI) is the newest form of imaging in general use today. In this imaging modality, a powerful magnet, up to 60,000 times as strong as the magnetic field of the earth... read more are not yet routinely used for the diagnosis of pancreatitis in dogs and cats, though they may hold promise for the future.
Several diagnostic markers for pancreatitis have been evaluated in dogs and cats. The clinical usefulness of serum amylase activity is limited in dogs and cats. Serum lipase activity can be measured using various substrates, but none of these are specific for the measurement of pancreatic lipase activity. Some studies have suggested that DGGR and triolein may be better substrates to measure pancreatic lipase activity in serum, whereas other studies come to different conclusions, with a high rate of false-positive results.
In contrast, the measurement of pancreatic lipase immunoreactivity (PLI) is specific for the measurement of pancreatic lipase concentration in serum and is thus the most specific diagnostic test for pancreatitis. It is also highly sensitive. In-clinic tests for the semiquantitative evaluation of serum pancreatic lipase immunoreactivity (ie, SNAP cPL and SNAP fPL) are available. A negative semiquantitative test suggests that pancreatitis is very unlikely, whereas a positive test suggests pancreatitis. In the latter case, pancreatic lipase immunoreactivity (PLI) concentration should be measured in a serum sample (ie, by Spec cPL and Spec fPL) and evaluated to confirm the diagnosis and to determine a baseline concentration. This also allows the use of serum PLI concentration as a monitoring tool for the disease. It is important to remember, as for any disease, that no test should be used in isolation for diagnosis, and all clinical findings should be used in conjunction to arrive at the most appropriate diagnosis.
More recently, several quantitative in-house assays for the measurement of serum PLI concentration, mainly in dogs, have become available. These assays have either not yet been analytically validated in the primary literature or have failed analytic validation and thus cannot be recommended for routine use at this time.
Pancreatic cytology or histopathology can also be used to definitively diagnose pancreatitis. Fine-needle aspiration of the pancreas is safe and can show acinar cells and inflammatory cells, allowing a definitive diagnosis of pancreatitis. However, lack of inflammatory cells does not exclude pancreatitis, because the inflammatory infiltrate can be highly localized. Pancreatic biopsy for histopathologic evaluation may be associated with a higher risk of pancreatitis than fine-needle aspiration (due to more aggressive pancreatic handling and longer anesthesia). Also, even if the presence of pancreatitis seems obvious on macroscopic examination of the pancreas, a biopsy specimen should be collected because the definitive diagnosis of pancreatitis requires the identification of an inflammatory infiltrate during histopathology. Finally, animals with severe pancreatitis are often poor anesthetic risks, and exploratory laparotomy or even fine-needle aspiration may not be justified.
Acute cases: identification and management of underlying causes and risk factors, supportive care, and symptomatic care
Chronic cases: as above, with monitoring of progression, and, if there is no improvement, trial therapy with an immunosuppressive agent
The mainstay of therapy of severe pancreatitis is supportive care with fluid therapy, vigorous monitoring, and early intervention to prevent systemic complications. Fluid therapy should be based on calculation of degree of dehydration (to be replaced over 4–8 hours if there is no contraindication), maintenance, and ongoing losses (eg, due to vomiting or diarrhea).
In those few cases in which the cause is known, specific therapy against the inciting cause may be initiated. Antibiotics are of questionable value and should not be used routinely.
Resting the pancreas is suggested only if the animal vomits uncontrollably (ie, the animal vomits frequently and violently despite appropriate antiemetic therapy). In fact, early nutritional support is considered a key component of successful treatment of human patients with severe pancreatitis. Also, enteral nutritional support is considered superior to parenteral nutrition. Animals that vomit should be treated with an antiemetic, such as maropitant (NK1 antagonist), ondansetron, or dolasetron (HT3 antagonists), or in most animals a combination of both. Even animals that do not actively vomit may benefit from such antiemetic support, because they may be nauseated, leading to poor or absent appetite. Metoclopramide is not considered effective as an antiemetic agent and should not be used in these animals.
Abdominal pain should be assumed to be present and treated until contrary evidence is available. Intermittent meperidine, butorphanol, or buprenorphine may be used in animals with mild or moderate abdominal pain. Animals with severe pain are often treated with a constant-rate infusion of an opioid, such as morphine, fentanyl, or methadone, or with a combination therapy of fentanyl, ketamine, and lidocaine. Many other treatments have been investigated in dogs, cats, and people, but unfortunately none has been shown to be useful.
Recently, a new medication for the specific treatment of acute pancreatitis, Brenda Z, an LFA-1 antagonist, has been licensed for the treatment of acute canine pancreatitis in Japan. Although initial reports are very promising, this medication has not yet been licensed for use in either North America or Europe.
Animals with mild forms of pancreatitis should be carefully assessed for the presence of risk factors (eg, hypertriglyceridemia, hypercalcemia Hypercalcemia in Dogs and Cats Hypercalcemia can be toxic to all body tissues, but major deleterious effects occur in the kidneys, nervous system, and cardiovascular system. The development of clinical signs from hypercalcemia... read more , history of medications that can cause pancreatitis) and concurrent diseases (eg, cholangitis Feline Cholangitis/Cholangiohepatitis Syndrome Feline cholangitis/cholangiohepatitis syndrome (CCHS) is the most common acquired inflammatory liver disease in domestic cats. Both cholangitis and cholangiohepatitis are more common in cats... read more , hepatitis, inflammatory bowel disease Chronic Enteropathies in Small Animals Chronic enteropathies last 3 weeks or longer and include GI signs such as vomiting, anorexia, and diarrhea. Diagnosis is typically based on history, clinical signs, and response to treatment... read more , diabetes mellitus Diabetes Mellitus in Dogs and Cats Diabetes mellitus is a common endocrine disease in dogs and cats, occurring in about 1 of every 300 patients. Clinical signs reflect hyperglycemia with resultant glycosuria. Diagnosis is made... read more ). In dogs, feeding an ultra-low-fat diet is crucial for treatment success. In cats, a moderately fat-restricted diet is recommended. Antiemetic drugs (see above) and appetite stimulants (ie, capromorelin in dogs, mirtazapine in cats) are helpful for animals that may not eat due to nausea.
If animals with chronic pancreatitis do not respond to therapy, a trial with prednisone (dogs), prednisolone (dogs and cats), or cyclosporine (dogs or cats) may be attempted. Cyclosporine is advantageous in animals with concurrent diabetes mellitus, because it has a smaller impact on insulin resistance than glucocorticoids.
The prognosis in mild cases of pancreatitis is good, but the prognosis in severe cases of pancreatitis is guarded in both dogs and cats. Systemic complications such as hypothermia, acidosis, hypocalcemia, and single- or multiple-organ failure are considered risk factors for a poor outcome. It can be challenging to identify severe cases early during the disease process and prevent complications in those animals.
A diagnosis of pancreatitis is made by integrating clinical findings, imaging findings, and results from measurement of serum pancreatic lipase immunoreactivity.
Management of acute pancreatitis is centered around diagnosis and treatment of potential underlying causes and risk factors, supportive care, and symptomatic care.
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