There are two types of exocrine secretions produced by the
pancreas. Acinar cells produce digestive
enzymes: amylase, lipase, and peptidases. Pancreatic
peptidases are produced as inactive zymogens that are only
activated after they reach the duodenum (see webpage on Zymogens).
other major secretion is bicarbonate (HCO3-),
is produced by the duct cells. The bicarbonate acts
to neutralize acidic chyme coming from the stomach. As well,
fluid that is produced by duct cells flushes enzymes and zymogens
out into the large pancreatic duct.
At right is a picture from one of our histology slides. The majority of exocrine tissue in the pancreas consists of acinar cells, which are the dark clusters visible throughout. The pointer points to a small intercalated duct. These ducts receive the acinar cell secretions, and secrete bicarbonate and fluid. They connect to larger ducts that eventually lead to the large pancreatic duct that has its outlet at the duodenal papilla.
figure at left summarizes the regulation of pancreatic
secretion. A small amount of pancreatic secretion occurs due
to neural inputs that are triggered by cephalic phase and gastric
phase stimuli. The majority of pancreatic secretion arises
from intestinal phase stimuli (when chyme reaches the
duodenum). The hormones secretin and cholecystokinin
(CCK) are released by endocrine cells that are located in
the duodenal epithelium.
As shown in the figure, secretin release is triggered by H+ ions (low pH). Secretin then travels via the circulation to stimulate bicarbonate secretion by duct cells. CCK release is triggered by digestive products (fats and peptides). CCK then travels via the circulation to stimulate secretion by acinar cells.
Secretion of bicarbonate by duct cells depends upon the protein CFTR. In the fall, we learned that CFTR is a chloride channel that provides the rate limiting step in fluid secretion in the small intestine (see webpage on Epithelial Transport). But it turns out the CFTR protein is also a bicarbonate channel. When the CFTR protein is defective, as it is in patients with cystic fibrosis, duct cell secretion is disrupted. This causes a lack of fluid secretion to flush out pancreatic zymogens, blockage of pancreatic ducts, and inappropriate activation of trypsin in the pancreas. The result is inflammation with damage to acinar and duct cells, which may be replaced by connective tissue. Patients with severe mutations of CFTR (little or no CFTR function) are often born with pancreatic insufficiency, meaning their pancreas does not release sufficient quantities of digestive enzymes. They will have have a failure to thrive, and need to be treated with digestive enzyme supplements. Less severe mutations in CFTR (with some channel function) still increase the risk for pancreatitis. You can review the clinical effects of the CFTR mutation on the webpage Clinical Examples: Epithelial Transport (from Fall Quarter).