Pancreatitis in dogs and cats (Proceedings)

The pancreas has both endocrine and exocrine functions. The endocrine pancreas consists of the islets of Langerhans and is particularly important to carbohydrate metabolism. Diseases of the endocrine pancreas include diabetes mellitus and hormone-producing tumors such insulinomas and glucagonomas. The exocrine pancreas consists of the acinar and ductular cells. The exocrine pancreas produces enzymes, zymogens and other products that aid in the digestion of food. Diseases of the exocrine pancreas include pancreatitis, exocrine pancreatic insufficiency and carcinomas.

Pathophysiology

Pancreatitis is thought to be due to the premature activation of zymogens within the pancreas. Zymogens are synthesized as inactive enzymes to prevent cell membrane damage within the pancreas. These zymogens are activated in the duodenum. Pancreatitis is the result of fusion of lysosomal enzymes with zymogen granules in the acinar cells. As a result, autodigestion of the pancreas occurs, inflammatory cells are recruited, free radicals produced, and inflammatory mediators are produced. As a result further damage and additional inflammation occurs. There are several mechanisms in place that help prevent premature activation of the granules, pancreatitis and systemic inflammation. These include storage of zymogens in granules, co-secretion of pancreatic secretory trypsin inhibitor (PSTI), secretion into the duodenum as inactive zymogens, the pancreatic duct, the sphincter of Oddi, and circulating protease inhibitors.

Acute and chronic forms of pancreatitis have been described in dogs and cats. In acute pancreatitis inflammation is present but fibrosis and atrophy are absent. With chronic pancreatitis fibrosis and pancreatic atrophy are present. Both forms may have neutrophilic and lymphocytic inflammatory cell infiltrates, edema and necrosis.

Etiology

Most cases of pancreatitis are idiopathic. There are several conditions which have been associated with the development of pancreatitis including dietary indiscretion, inflammatory bowel disease, biliary disease, hyperlipidemia, certain drugs, hypercalcemia, zinc toxicosis, organophosphate poisoning, obesity, hyperadrenocorticism, hypothyroidism, diabetic ketoacidosis, trauma, ischemia, Babesia canis, Toxoplasma gondii, and flukes. In the Miniature Schnauzer mutations in the SPINK 1 gene, which encodes for PSTI, have been identified. The significance of this is unknown but PSTI is a trypsin inhibitor cosecreted with trypsinogen that is thought to help deter premature activation of the zymogens.

Clinical presentation

There is no age or sex predisposition. All breeds can be affected but there is an increased incidence in Miniature Schnauzers, Shetland Sheepdogs, Yorkshire terriers, poodles, Bichon frises, maltese, shih tzus, Samoyeds and many others.

The clinical presentation is variable but animals with acute pancreatitis tend to have more severe signs than those with chronic pancreatitis. In dogs anorexia, vomiting, lethargy, and abdominal pain are common. Fever and diarrhea are not as common. Most cats have very non-specific signs including anorexia and lethargy. Less common are weight loss, icterus, fever, hypothermia, abdominal pain, and diarrhea. In dogs and cats signs of systemic inflammation such a dyspnea and cardiac arrhythmias as well as circulatory shock may be present.

Diagnosis

Bloodwork may reveal a relative polycythemia, anemia, neutrophilia with a left shift, thrombocytopenia, elevated liver enzymes, azotemia, decreased albumin, and hypocalcemia on the CBC and biochemical profile.

Tests used historically to diagnose pancreatitis are serum amylase and lipase, trypsinlike immunoreactivity and pancreatic lipase immunoreactivity. Amylase and lipase lack sensitivity and specificity in dogs and cats for detecting pancreatitis. Trypsinlike immunoreactivity is a sensitive test for the diagnosis of exocrine pancreatic insufficiency but not for pancreatitis in the dog and cat. Pancreatic lipase immunoreactivity is the most sensitive and specific test for diagnosing pancreatitis in the dog and cat. IDEXX Laboratories has developed a commercial Spec cPL for dogs, a SNAP cPL for dogs, and SNAP fPL for cats making testing more readily available. The SNAP tests only read as positive or negative whereas the PLI and Spec cPL provide actual values.

Radiographs are not preferred but may be valuable in eliminating other causes of clinical signs. Classic radiographic changes seen in the dog, but not the cat, include decreased abdominal detail, cranial abdominal mass effect, widening of the juncture between the pylorus and duodenum, displacement of the stomach, and ileus. Abdominal ultrasound is preferred. The pancreas may be surrounded by fluid, enlarged, heterogenous, hypoechoic, or contain fluid-filled structures. A hypoechoic pancreas with hyperechoic peripancreatic fat is suggestive of pancreatic necrosis. A heterogenous pancreas is more suggestive of fibrosis seen with chronic pancreatitis. Unfortunately for cats ultrasonographic changes of the pancreas are not as reliable indicators of pancreatitis. Ultrasound has the additional advantage of the ability to sample the pancreas and visualize other abdominal structures. Pancreatic cytology is done with needle aspirates. Pancreatic aspirates may be helpful in cases of acute pancreatitis by identifying pancreatic necrosis. Aspirates are also useful in diagnosing pancreatic neoplasia. Cross-sectional imaging has not been studied extensively in dogs and cats for the diagnosis of pancreatitis.

Histologic examination of the pancreas is considered the gold standard for diagnosis. It is possible to miss significant lesions with biopsy and lesions consistent with pancreatitis are found in animals with no clinical signs. This again emphasizes the importance of performing diagnostic tests in animals with clinical signs. Unfortunately there is concern that in obtaining biopsies a patient will be at risk for developing more severe pancreatitis. Biopsies can be taken surgically or laparoscopically.

Treatment

Treatment for pancreatitis has focused on supportive care directed towards animals with more acute, severe forms of pancreatitis. Supportive care primarily consists of fluid therapy, nutritional support, pain management, antiemetics, and plasma administration. The goals of fluid therapy are to correct fluid deficits, electrolyte abnormalities and metabolic disturbances as well as to maintain perfusion to the pancreas.

Traditionally, a 4 day NPO was recommended for dogs with acute pancreatitis but this is no longer the case. Currently the recommendation is to provide enteral nutrition to dogs and cats as soon as possible. This means that animals that are not vomiting should be fed. Animals that are vomiting should have the vomiting controlled so feeding can be started. Only animals in which aggressive antiemetic therapy fails to control vomiting should enteral feeding be delayed. Traditionally, total parenteral nutrition or jejunostomy tube feedings were recommended in order to avoid the pancreas. Jejunostomy tubes require surgical placement and limit the feeding to liquid diets as a continuous rate infusion. Total parenteral nutrition requires placement of central catheters, diligent catheter care and formulation of solutions. Nasoesophageal, esophagostomy and gastrostomy tube feedings are considered reasonable options for feeding. Nasoesophageal tubes can be placed without sedation or anesthesia. Esophagostomy and gastrostomy tubes require anesthesia for placement but have the advantage of more dietary options. It is still recommended that diets selected should be low in fat.

Pain management is very important in animals with pancreatitis. Unfortunately we as veterinarians are not always good at assessing pain in our patients. Opioids and synthetic opioids are commonly used such as butorphanol, buprenorphine, morphine, fentanyl, and tramadol. Fentanyl and lidocaine constant rate infusions are being utilized more commonly with severe abdominal pain.

Antiemetics are necessary in many cases of pancreatitis. The 5HT-3 antagonists (ondansetron, dolasetron) and NK1 antagonist (maripotant) are used most commonly.

The administration of plasma is controversial. Plasma contains α2- macroglobulin, clotting factors and albumin which may be beneficial in pancreatitis. The plasma α2-macroglobulins can replace depleted endogenous α2-macroglobulins. Pancreatitis can cause systemic inflammation and consumption of clotting factors. Albumin can help maintain oncotic pressure and perfusion to the pancreas. Plasma is most commonly used in more severe forms of acute pancreatitis.

Antibiotic use is also controversial. Pancreatitis is a sterile inflammatory disease in most dogs and cats so antibiotics are not indicated. Even when pancreatic abscesses are found, they are usually sterile. The use of antibiotics should be justified by a documented or highly suspected bacterial infection.

Pancreatic pseudocysts and abscesses are uncommon manifestations of chronic pancreatitis in dogs and cats. Diagnosis is made utilizing ultrasound and cytology. Abscesses should be cultured but are usually sterile. Surgery and antimicrobials are indicated when an infection is present but medical management with ultrasound guided drainage is recommended for pseudocysts and sterile abscesses.

Although supportive care has been the focus in treating pancreatitis in dogs and cats, any identifiable underlying disease or predisposing condition should be addressed. In cats there is particular concern about a relationship between pancreatitis (particularly chronic), cholangitis and inflammatory bowel disease due to the anatomy. In dogs ascending inflammation or bacteria may also be responsible for pancreatic and hepatobiliary disease. If there is any indication of diseases in these other organs then a diagnostic evaluation should be considered.

Prognosis

The prognosis is guarded for dogs and cats with acute and chronic pancreatitis primarily because of the development of systemic complications. Complications of acute and chronic pancreatitis include DIC, acute renal failure, respiratory failure, myocarditis, and pancreatic encephalopathy. Cats with chronic pancreatitis may develop exocrine pancreatic insufficiency and diabetes mellitus.

References

Steiner JM. Canine pancreatic disease in Textbook of Veterinary Internal Medicine 7th ed. Ettinger SJ, Feldman EC (eds) Elsevier 2010. pp 1695 – 1704.

Steiner JM. Exocrine pancreas in Small Animal Gastroenterology. Steiner JM (ed). 2008 Schlütersche. pp 283 – 306.

Washabau RJ. Feline pancreatic disease in Textbook of Veterinary Internal Medicine 7th ed. Ettinger SJ, Feldman EC (eds) Elsevier 2010. pp 1705 - 1709