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Feline pancreatitis (Proceedings)
Cats have a different embryological development and anatomy of the pancreas from other species. In cats, unlike other species, the pancreatic duct is the main functional duct; the accessory pancreatic duct usually does not persist. In dogs the pancreatic duct is of minor importance and may be absent.
Anatomy and Physiology
Cats have a different embryological development and anatomy of the pancreas from other species. In cats, unlike other species, the pancreatic duct is the main functional duct; the accessory pancreatic duct usually does not persist. In dogs the pancreatic duct is of minor importance and may be absent. The pancreatic duct enters the duodenum through the major duodenal papilla. In cats this is the main and often only pancreatic duct opening into the duodenum. It enters the duodenum jointly with the bile duct.
The exocrine pancreas has two primary roles: to aid the digestion and assimilation of food and to protect against autodigestion. Pancreatic secretions include digestive enzymes to break down lipids, proteins, and polysaccharides in the proximal duodenum. These enzymes include trypsin, chymotrypsin, kallidrein, elastases, carboxypeptidases, and lipase. These enzymes are secreted in an inactive form as a zymogen or proenzyme. Trypsin, the active form of trypsinogen, is the only activated enzyme that can activate both itself and other zymogens. Bicarbonate is secreted to neutralize gastric acid when food boluses enter the duodenum from the stomach. Colipase is secreted to facilitate the action of lipase in the breakdown of fats. Factors are also secreted that enable the absorption of zinc and cobalamin (Vit B12). Pancreatic secretions inhibit bacterial growth in proliferation and promote normal degradation of exposed brush border enzymes. Protection against autodigestion is complex and involves many safeguards.
• Pancreatic enzymes are synthesized, stored, transported, and secreted into the duodenum in the inactive form, zymogen or proenzyme. The zymogens are activated in the duodenum by the brush border enzyme, enterokinase. Enterokinase is 2000 times more effective at activating trypsinogen that trypsin.
• In the pancreatic acinar cells the zymogens are packaged in lipid structures (vesicles/granules) segregated from lysosomal enzymes that may activate the zymogens.
• A trypsin inhibitor, pancreatic trypsin secretory inhibitor (PTSI) is included within the zymogen granules that can inactivate trypsin that may have been prematurely activated within the granule. PSTI is located in pancreatic ducts and within the acinar cells in addition to zymogen granules.
• Antiproteases such as α-antitrypsin, α-macroglobulin, and anti-chymotrypsin circulate in the plasma and protect against proteases that escape into circulation.
• Muscle sphincters in the pancreatic ducts help prevent reflux of enterokinase and duodenal contents into the pancreas.
• Maintenance of a high alkaline ductular flushing. The alkalinity is maintained by bicarbonate secretion through the cystic fibrosis transmembrane conductance regulatory (CFTR). In humans mutation of CFTR can lead to chronic pancreatitis.
Secretion of zymogen granules is mediated by neural and humoral mechanisms of which the humoral mediators, secretin and cholecystokinin, are the most important in cats in stimulating zymogen secretion. Secretin stimulates a bicarbonate rich pancreatic juice and cholecystokinin, an enzyme rich pancreatic juice. The pancreas secretes mainly in response to food, however, a small amount of secretion occurs into the duodenum during fasting accounting for approximately 2% of bicarbonate and 10% of enzymes that are secreted in response to food.
Pancreatitis results from failure of protective mechanisms of the pancreas resulting in zymogen activation within the pancreas. Most agree that trypsin activation within the pancreas plays a major role in development and propagation of pancreatitis. Trypsin, as stated previously, is capable of activating itself and other zymogens. Pancreatitis is a multifactorial and complex process; the initiating events are not completely understood. Acute pancreatitis can result from the abnormal fusion of lysosomal and zymogen granules within the acinar cells and may also result from inappropriate duodenal reflux into the pancreas. In humans chronic or recurrent acute pancreatitis has been associated with mutations in the PTSI gene and CFTR gene.
Once zymogen activation has occurred, the active enzymes, most importantly proteases and lipases, enter the interstitium of the pancreas and the peritoneal cavity. The activated pancreatic enzymes damage pancreatic tissue and this damage is amplified by free radical-associated damage and increased permeability due to endothelial membrane damage. The increased permeability can lead to pancreatic edema, decreased microvascular circulation, increased free-radical stasis, and local ischemia leading to worsening of inflammation and parenchymal damage.
Circulating proteases can overwhelm the circulating anti-proteases (α-antitrypsin and α-macroglobulin). Circulating proteases can activate complement, fibrinogen, coagulation, and kinin cascades. This may lead to hypotensive shock, disseminated intravascular coagulation, multiple organ dysfunction syndrome, and death.
Classification of Pancreatitis
Pancreatitis can encompass a spectrum of clinical presentations: subclinical, mild and self limiting, or severe. Severe cases can be associated with pancreatic necrosis and abscessation, formation of a pseudocyst, shock, DIC, embolic disease, ARDS, SIRS, MODS, and death. It is important to remember that acute pancreatitis does not necessarily equate with severe disease. Human classifications for pancreatitis have been adapted for veterinary use. Following the human system, feline pancreatitis can be divided into acute and chronic forms based on the presence, as in chronic, or absence, as in acute, of permanent histopathologic changes such as fibrosis or acinar atrophy. Other histologic findings such as pancreatic cell necrosis, peripancreatic fat necrosis, predominant type of cell infiltration and clinical criteria are often to further classify the disease process in cats. Pancreatic cell necrosis and peripancreatic fat necrosis are seen in acute disease. Chronic pancreatitis can be defined as a continuous usually progressive inflammation of the pancreas characterized by permanent damage of the pancreatic structure that can lead to irreversible impairment of pancreatic exocrine and possibly endocrine function. Both acute and chronic forms of pancreatitis may be clinically mild or severe although chronic pancreatitis is usually considered to be milder than acute or even sub-clinical. Acute necrotizing pancreatitis is impossible to distinguish from chronic pancreatitis in the cat based upon history, physical examination findings, and abdominal imaging.
The predominant inflammatory cellular infiltrate is often used to describe pancreatitis. Suppurative inflammation is considered consistent with acute disease and lymphoplasmacytic inflammation is considered a component of chronic disease. Necrosis as implied earlier is also considered a component of acute disease. Some may show evidence of fibrosis and concurrent cell necrosis and the term chronic active pancreatitis has been adapted by some to describe this occurrence. Chronic pancreatitis seems to be more common in cats and has been reported in 60% of all pancreatitis cases in cats.1 Chronic active pancreatitis in cats has been reported to occur in 9.6% of pancreatitis cases in cats and acute pancreatitis accounting for approximately 6.1% of cats with pancreatitis.1 The true prevalence of pancreatitis in cats is unknown.
In the vast majority of cats the cause of pancreatitis cannot be determined and it is considered to be idiopathic. Factors that have been associated with the development of pancreatitis in cats include infectious agents such as Toxoplasma gondii, Eurytrema procyonis (pancreatic fluke), Ampimerus pseudofelineus (liver fluke), virulent feline calicivirus, feline infectious peritonitis virus, feline parvovirus, feline herpesrvirus. Biliary tract disease including cholangitis and obstruction, and inflammatory bowel disease have been shown to have an association with the development of pancreatitis in cats. Triaditis has been used to describe these three disease processes occurring simultaneously. Pancreatic duct obstruction, hypotension, trauma, organophosphates, and hypercalcemia (in the experimental setting) are other risk factors that have been identified for pancreatitis in cats. Hepatic lipidosis can be seen concurrently with pancreatitis.
Clinical Features and Diagnostics
Any cat of any age, breed, or sex can develop pancreatitis. Some studies have found older cats to be over-represented especially in the chronic form of pancreatitis. Domestic shorthaired cats and Siamese have been reported to be at increased risk in some studies but not in others. In cats mild pancreatitis may not be detected by an owner. As stated previously acute and chronic pancreatitis in cats cannot be differentiated clinically (clinical signs, duration of illness); although chronic pancreatitis is believed to be more clinically mild and acute more clinically severe.
Clinical signs reported in cats with pancreatitis include most commonly anorexia (complete or partial) 97%, lethargy 100%, and less commonly, as opposed to canines, vomiting 35%, abdominal pain 25%, and diarrhea 15%.2 Physical examination findings include dehydration, pallor, icterus, tachypnea, dyspnea, hypothermia, fever, abdominal pain, and palpable abdominal mass. Severe systemic complications occasionally are seen in cats including DIC, PTE, cardiovascular shock, MODS.
Complete blood count, serum biochemical profile, and urinalysis should be performed in cats suspected of having pancreatitis, however findings are usually non-specific, may be normal, and are not confirmative of pancreatitis. CBC changes can include a leukocytosis or leucopenia, regenerative anemia or hemoconcentration. Increased ALT, ALP activities and bilirubin may be seen which may reflect concurrent inflammatory hepatic disease or hepatic lipidosis. Hypercholesterolemia, hyperglycemia, and hypoalbuminemia may be seen. Hypocalcemia should raise suspicion of pancreatitis especially in a cat showing consistent clinical signs; and, cats with pancreatitis and low ionized calcium may have a poorer prognosis. Amylase and lipase activities are not valuable in the diagnosis of feline pancreatitis. The sensitivity of the fTLI is low for the diagnosis of pancreatitis in cats (28%-33%) and its specificity is questionable. The fPLI (Gastrointestinal Laboratory Texas A&M University) has a reported sensitivity of 100% for cats with moderate to severe pancreatitis and 54% for histopathologically mild pancreatitis, and an overall sensitivity of 67%.12 The recently available fPL (IDEXX labs) is reported to have a sensitivity of 79% and specificity of 82%.3
Abdominal radiographs lack sensitivity and specificity for diagnosing feline pancreatitis. The most common radiographic abnormality seen is decreased detail/contrast in the cranial abdomen, ileus, hepatomegaly, and a cranial abdominal mass. Abdominal ultrasound has a reported sensitivity that ranges from 25% to 67%.10,11,12 The variation reflects the skill of the examiner, the equipment used, and the severity of lesions. The most common and most specific abnormal ultrasound findings in pancreatitis include hypoechoic pancreas and hyperechoic peripancreatic mesentery. Other less common and less specific findings include abdominal effusion, an enlarged pancreas, hepatomegaly, cavitary lesions of the pancreas (pseudocysts), calcification of the pancreas, and hyperechoic areas of the pancreas indicating fibrosis. Abdominal ultrasound is helpful in evaluating for concurrent disease and in guiding FNAs of the pancreas to evaluate for cytologic evidence of inflammatory cells and try to differentiate pancreatitis from pancreatic neoplasia. Lack of cytologic evidence of inflammation does not rule out pancreatitis. Ultrasound guided fine needle aspiration can be used for diagnosing and managing via drainage pseudocysts and abscesses. Computed tomography is the gold standard for diagnosis of pancreatitis in humans. Early studies have shown that CT is not very useful for the diagnosis of pancreatitis in cats.
Visualization of the pancreas can be made possible during laparotomy or laparoscopy. Gross lesions suggestive of pancreatitis in the cat may include peripancreatic fat necrosis, pancreatic hemorrhage and congestion, and a dull granular capsular surface. Histopathology is the only way to differentiate between acute and chronic pancreatitis. There are limitations to biopsy and histopathology as inflammatory lesions are often localized and can be missed. Surgery is invasive and requires anesthesia and is risky in patients with pancreatitis especially in cats that are not hemodynamically stable. If taken to surgery, it is recommended that hepatic and intestinal biopsies be obtained because of the triaditis phenomenon.
Potential etiologic factors should be investigated and managed. Concurrent disease should be treated. Treatment of pancreatitis is based on supportive care. Cats presenting with pancreatitis are often time dehydrated. Aggressive fluid therapy is important to restore/maintain pancreatic perfusion. Intravenous replacement crystalloid fluids are recommended and colloids solutions may be necessary. Electrolytes should be monitored and if deficient, replaced. Hypokalemia is not uncommonly seen due to lack of intake or losses via vomiting/diarrhea. Serum calcium should be monitored as well.
Early nutritional support is very important for cats with pancreatitis. If a cat is not vomiting, it should be fed orally. If vomiting is severe, food and water may be restricted for 12 to 24 hours and antiemetics given to control vomiting. If after this short period, water does not cause vomiting, small amounts of food may be offered. If a cat is anorexic for more than 2-3 days (including time prior to presentation to the hospital) placement of a feeding tube is recommended. Depending on the patients' stability and risks of anesthesia nasoesophageal, esophagostomy, gastrostomy, or jejunostomy tubes can be considered. Enteral nutrition is preferred to parenteral nutrition (total or partial parenteral nutrition) for the prevention/treatment of concurrent hepatic lipidosis and to maintain nutrition to enterocytes to decrease the likelihood of bacterial translocation.
Although in published studies abdominal pain does not appear to be a very common finding in feline pancreatitis, this may reflect our inability to detect pain in cats as well as the stoic nature of cats. As such, analgesic therapy is important in the management of pancreatitis even when pain is not identified. Intermittent injections of buprenorphine (.007-.015 mg/kg IV or IM q 6-8 hrs), meperidine (2-5 mg/kg IV or IM q 2-6 hrs), or butorphanol 0.2-0.8 mg/kg IV or SQ q 2-6 hrs) may be used initially for pain control. Butorphanol given as a constant rate infusion may also provide antiemetic properties. Transdermal fentanyl patches may be used as well as a fentanyl constant rate infusion with or without lidocaine and ketamine.
Antiemetic therapy is indicated in cases where vomiting or nausea is present. The 5-HT3 antagonists such as dolasetron (Anzemet 0.6 mg/kg IV, SQ, PO q 12 hrs) and ondanestron (Zofran 0.1-0.2 mg/kg IV q 6-12 hrs) and α2-adrenergic antagonists such as chlorpromazine (0.2-0.5 mg/kg IM or Sq q 8 hrs) seem to be most effective in cats. The dopaminergic antagonists such as metoclopramide (0.2-0.5 mg/kg IV, IM, SQ q 6-8 hrs or 0.04-0.08 mg/kg/hr constant rate infusion) may be less effective. Maropitant, although not licensed for use in cats seems to be effective at a similar dose used in dogs (0.5 - 1 mg/kg SQ).
Antibiotic administration is controversial for feline pancreatitis. Antibiotics are recommended in cases with infectious complications are present such as pancreatic abscess and concurrent suppurative cholangitis or if infectious complications suspected (fever, melena, etc). Enrofloxacin (5 mg/kg IV, PO q 24 hrs) and ampicillin sodium (22 mg/kg IV, IM, SQ q 8 hrs) or ampicillin sodium/sublactam sodium (20-50 mg/kg IV q 8 hrs) or cefotaxime (20-80 mg/kg IV or IM q 6 hrs) may be good choices.
Pancreatic pseudocysts may develop as a complication of pancreatitis and can cause necrosis of pancreatic tissue. In humans percutaneous drainage seems to be the treatment of choice. Surgery for pseudocysts and pancreatic abscesses are not well described in cats demonstrating a lack of experience. Surgery may be considered for pancreatic abscesses especially infected abscesses or when extrahepatic bile duct obstruction occurs secondary to pancreatitis.
The prognosis for cats is variable. In cats with acute pancreatitis, a decreased ionized calcium (<1 mmol/L) or concurrent hepatic lipidosis have been reported to be associated with a poor prognosis.
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