Basic Stimuli That Cause Pancreatic Secretion
Three basic stimuli are important in causing pancreatic secretion:
1. Acetylcholine, which is released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system
2. Cholecystokinin, which is secreted by the duodenal and upper jejunal mucosa when food enters the small intestine
3. Secretin, which is also secreted by the duodenal and jejunal mucosa when highly acidic food enters the small intestine
The first two of these stimuli, acetylcholine and chole cystokinin, stimulate the acinar cells of the pancreas, causing production of large quantities of pancreatic diges tive enzymes but relatively small quantities of water and electrolytes to go with the enzymes. Without the water, most of the enzymes remain temporarily stored in the acini and ducts until more fluid secretion comes along to wash them into the duodenum. Secretin, in contrast to the first two basic stimuli, stimulates secretion of large quantities of water solution of sodium bicarbonate by the pancreatic ductal epithelium.
Multiplicative Effects of Different Stimuli. When all the different stimuli of pancreatic secretion occur at once, the total secretion is far greater than the sum of the secretions caused by each one separately. Therefore, the various stimuli are said to “multiply,” or “potentiate,” one another. Thus, pancreatic secretion normally results from the combined effects of the multiple basic stimuli, not from one alone.
Phases of Pancreatic Secretion
Pancreatic secretion, as with gastric secretion, occurs in three phases: the cephalic phase, the gastric phase, and the intestinal phase. Their characteristics are described in the following sections.
Cephalic and Gastric Phases. During the cephalic phase of pancreatic secretion, the same nervous signals from the brain that cause secretion in the stomach also cause acetylcholine release by the vagal nerve endings in the pancreas. This signaling causes moderate amounts of enzymes to be secreted into the pancreatic acini, accounting for about 20 percent of the total secretion of pancreatic enzymes after a meal. However, little of the secretion flows immediately through the pancreatic ducts into the intestine because only small amounts of water and electrolytes are secreted along with the enzymes.
During the gastric phase, the nervous stimulation of enzyme secretion continues, accounting for another 5 to 10 percent of pancreatic enzymes secreted after a meal. However, again, only small amounts reach the duodenum because of continued lack of significant fluid secretion.
Intestinal Phase. After chyme leaves the stomach and enters the small intestine, pancreatic secretion becomes copious, mainly in response to the hormone secretin.
Secretin Stimulates Copious Secretion of Bicarbonate Ions, Which Neutralizes Acidic Stomach Chyme. Secretin is a polypeptide containing 27 amino acids (with a molecular weight of about 3400). It is present in an inactive form, prosecretin, in so-called S cells in the mucosa of the duodenum and jejunum. When acid chyme with a pH less than 4.5 to 5.0 enters the duodenum from the stomach, it causes duodenal mucosal release and activation of secretin, which is then absorbed into the blood. The one truly potent constituent of chyme that causes this secretin release is the hydrochloric acid from the stomach.
Secretin in turn causes the pancreas to secrete large quantities of fluid containing a high concentration of bicarbonate ion (up to 145 mEq/L) but a low concentration of chloride ion. The secretin mechanism is especially important for two reasons: First, secretin begins to be released from the mucosa of the small intestine when the pH of the duodenal contents falls below 4.5 to 5.0, and its release increases greatly as the pH falls to 3.0. This mechanism immediately causes copious secretion of pancreatic juice that contains abundant amounts of sodium bicarbonate. The net result is then the following reaction in the duodenum:
The carbonic acid then immediately dissociates into carbon dioxide and water. The carbon dioxide is absorbed into the blood and expired through the lungs, thus leaving a neutral solution of sodium chloride in the duodenum. In this way, the acid contents that are emptied into the duodenum from the stomach become neutralized, and thus further peptic digestive activity by the gastric juices in the duodenum is immediately blocked. Because the mucosa of the small intestine cannot withstand the digestive action of acid gastric juice, this protective mechanism is essential to prevent the development of duodenal ulcers, as is discussed in further detail in Chapter 67.
Bicarbonate ion secretion by the pancreas provides an appropriate pH for action of the pancreatic digestive enzymes, which function optimally in a slightly alkaline or neutral medium, at a pH of 7.0 to 8.0. Fortunately, the pH of the sodium bicarbonate secretion averages 8.0.
Cholecystokinin Contributes to Control of Digestive Enzyme Secretion by the Pancreas. The presence of food in the upper small intestine also causes a second hormone, cholecystokinin (CCK), a polypeptide containing 33 amino acids, to be released from yet another group of cells, the I cells, in the mucosa of the duodenum and upper jejunum. This release of CCK results especially from the presence of proteoses and peptones (products of partial protein digestion) and long-chain fatty acids in the chyme coming from the stomach.
CCK, like secretin, passes by way of the blood to the pancreas, but instead of causing sodium bicarbonate secretion, it mainly causes secretion of much more pancreatic digestive enzymes by the acinar cells. This effect is similar to that caused by vagal stimulation but is even more pronounced, accounting for 70 to 80 percent of the total secretion of the pancreatic digestive enzymes after a meal.
The differences between the pancreatic stimulatory effects of secretin and CCK are shown in Figure 1, which demonstrates (1) intense sodium bicarbonate secretion in response to acid in the duodenum, stimulated by secretin; (2) a dual effect in response to soap (a fat); and (3) intense digestive enzyme secretion (when pep tones enter the duodenum) stimulated by CCK.
Fig1. Sodium bicarbonate (NaHCO3), water, and enzyme secretion by the pancreas, caused by the presence of acid (HCl), fat (soap), or peptone solutions in the duodenum.
Figure 2 summarizes the more important factors in the regulation of pancreatic secretion. The total amount secreted each day is about 1 liter.
Fig2. Regulation of pancreatic secretion.
