2.1 Bicarbonate Secretion 

The pancreas secretes an isosmotic juice at a daily rate of 1,500-3,000 mL. It has a pH ranging between 8.0 and 8.5 and contains enzymes for fat, carbohydrate and protein digestion, water and electrolytes. The total concentration of the major anions Cl^- and HCO₃^- approaches 150 mEq/L (Figure 4). At maximum output, as would be observed following a meal, HCO₃^- concentration reaches 150 mEq/L, whereas Cl^- concentration is less than 50 mEq/L. This ratio is reversed at low flow rates. The high pH of the postprandial juice neutralizes acidic gastric chyme and raises duodenal contents to an optimal pH for enzymatic digestion. Pancreatic juice also contains Ca⁺⁺ and traces of Mg⁺⁺, HPO₄⁼ and SO₄⁼, although the role of these electrolytes is not known.

Four classes of enzymes are secreted by the pancreas; these are proteolytic, lipolytic, carbohydrate-hydrolyzing and nucleolytic enzymes.

Two of the proteolytic enzymes, trypsin and chymotrypsin, are secreted as zymogens. Both trypsinogen and chymotrypsinogen are activated by enterokinases that are secreted by the mucosa of the proximal intestine. Once trypsinogen is activated into trypsin, it in turn activates further zymogens. Trypsin and chymotrypsin are endopeptidases and constitute the largest component; they act by cleaving the peptide bonds of dietary protein, producing oligopeptides and amino acids. Other enzymes include carboxypeptidases A and B, and elastase.

Lipolytic enzymes are secreted in active form. Lipase is the major component. This enzyme hydrolyzes triglycerides to diglycerides, monoglycerides and fatty acids. Lipase acts as the oil-water interface of fat droplets. Its action is thus facilitated when the fat droplets are emulsified by bile salts and fatty acids. Bile salts also form molecular aggregates, micelles, to solubilize the products of lipolysis in the aqueous duodenal juice, removing them from the oil-water interface and so enhancing lipase activity. Colipase, a small-molecular-weight cofactor, is secreted by the pancreas. It combines with lipase to prevent the latter from being inhibited and removed from the oil-water interface by bile salts. Colipase also lowers the pH optimum of lipase from 8.5 to 6.5, which is the normal pH in the proximal intestine.

Amylase hydrolyzes starch to form maltose, maltotrioses and dextrins.

The fourth class of enzymes comprises nucleolytic enzymes, which hydrolyze the phosphodiester bonds that unite nucleotides in nucleic acid.

There are two patterns of pancreatic secretion. The first pattern is basal secretion, which is punctuated every 1 to 2 hours by bursts of increased bicarbonate and enzyme secretion that last 10 to 15 minutes. The second pattern is the postprandial stage, which results from a complex interaction of neural and hormonal mechanisms. It is divided into three phases. The cephalic phase occurs in response to the sight or taste of food and is probably mediated by the vagus nerve. The stimulation of cholinergic nerve fibers results in the production of enzymes and bicarbonate. The gastric phase occurs partially in response to distention of the stomach, which may stimulate gastrin release, probably by vagal reflexes. The released gastrin and neural reflexes stimulate acid secretion by the gastric parietal cells and pancreatic enzyme secretion. The intestinal phase, which is the most important, is initiated in response to acid entering the duodenum. When the pH of duodenal contents falls to 4.5 or below, secretin is released from the intestine; secretin in turn stimulates the pancreatic ducts to secrete bicarbonate. The presence of fatty acids, oligopeptides and amino acids results in the release of cholecystokinin (CCK), which stimulates the secretion of pancreatic enzymes. It appears that CCK and secretin each augments the action of the other on the secretion of both bicarbonate and enzyme.

The ultimate result of these interactions is food digestion and then absorption. Although secretin and cholecystokinin induce pancreatic secretion, other hormones -such as pancreatic polypeptide (PP) and peptide YY - inhibit basal and stimulated pancreatic secretion. Produced by the intestinal mucosa, they appear to act as a feedback mechanism to inhibit pancreatic production of further enzymes and electrolytes.

Stimulation of the vagus nerve induces bicarbonate secretion by the pancreas. This activity is thought to be in part mediated by vasoactive intestinal peptide (VIP). VIP hormone is present in vagal nerve endings and throughout the entire gastrointestinal tract. Its physiological role has not been established.