Feline pancreatitis (Proceedings)
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.