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Updated: 03/13/08 11:26 AM |
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| HOME | HEAL | EDUCATE | RESEARCH | DIRECTORY | OUTREACH |
Authors: G. Leinbach, B.J. Reid, D.R. Saunders, and T.D. Nguyen
Download Chapter ♦ Download Lecture Slides & Notes
Download Chapter ♦ Download Lecture Slides & Notes
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D. Regulation of Exocrine Function
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| Timing, pH, quantity are crucial |
The pancreas must deliver an appropriate quantity of enzymes, at the appropriate time, and at the optimal pH for the efficient digestion of nutrients delivered from the stomach to the duodenum. The acidic gastric chyme must be neutralized by pancreatic bicarbonate so that pancreatic enzymes can operate at their pH optima of 6-7, acid-peptic damage to small bowel mucosa is prevented, and solubility of bile salts is favored. Hormones and the nervous system participate in the three phases of pancreatic exocrine regulation, the cephalic, gastric, and intestinal phases.
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a. Cephalic Phase:
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Mainly cholinergic fibers
Abolished by vagotomy |
The cephalic phase, provoked by smell or taste of food, is exemplified by sham feeding (chewing food and spitting out the chewed food) which can stimulate about 25% of maximal pancreatic secretion. Stimuli reach the dorsal vagal complex to activate efferent vagal fibers. Acinar secretion is mainly stimulated in this phase. Acetylcholine is the major neurotransmitter involved.
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b. Gastric Phase:
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The gastric phase is initiated by gastric distension and by peptides and amino acids in the gastric lumen which activate vagovagal reflexes. This phase accounts for about 10% of meal-stimulated pancreatic secretion.
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c. Intestinal Phase:
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| Chief stimulants are H+, amino acids, fatty acids |
The intestinal phase is most important, and it is the most complex. Gastric chyme in the small intestinal lumen stimulates vagal afferents, and initiates the release of CCK and secretin from specific mucosal endocrine cells. Digestion products of fats (fatty acids containing more than twelve carbon atoms, mono-glycerides) and protein (amino acids and peptides) and, to a smaller extent, glucose promote CCK release. Gastric H+ (low pH) and to a lesser extent, fatty acids, and bile acids promote release of secretin. While secretin mainly stimulates ductal secretion of bicarbonate, and CCK mainly stimulates acinar secretion of enzymes, potentiation between these two hormones occurs so than an enzyme –and bicarbonate-rich juice is secreted.
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| CCK promotes pancreatic secretion by stimulating vagal and intra-pancreatic nerves |
Until recently, because CCK receptors are present on rat pancreatic acini, it was presumed that CCK, released into the bloodstream, circulates to the pancreatic acinar cells and affects these cells directly through CCK receptors. However, it appears that CCK receptors may not be expressed on human acinar cells. It is now proposed that CCK may interact with afferent vagal neurons to stimulate secretion through efferent vagal neurons. This model is consistent with the finding that the effects of physiologic concentrations of CCK on pancreatic enzyme secretion are blocked by atropine.
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| One inhibitory feedback loop involves trypsin |
Diversion of pancreatic juice from the intestine increases pancreatic secretion, an effect mediated by removing feedback inhibition of trypsin. During a meal, trypsin is occupied with ingested proteins and is not available for feedback inhibition. However, after dietary protein has been digested, trypsin then digests a peptide CCK-releasing factor, which is elaborated by endocrine cells in the duodenum. Less CCK is released as the amount of CCK-releasing factor in the lumen decreases.
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Figure 5 Feedback Regulation of Pancreatic Exocrine Secretion This figure summarizes the intestinal phase of stimulation of pancreatic secretion and the major pathways for regulation of pancreatic bicarbonate and enzyme secretion. Duodenal pH, determined by a balance of pancreatic HCO3 -and gastric HCl regulates the secretion, by intestinal endocrine S cells, of secretin. Secretin then circulates to the pancreas to stimulate, in an endocrine manner, HCO3-secretion from pancreatic duct cells. CCK-releasing factor (CCK-RF), present in the intestinal lumen, stimulates other intestinal endocrine cells to secrete CCK. In the fasting state, trypsin degrades CCK-RF to control pancreatic secretion; after a meal, trypsin binds to ingested proteins and does not attack CCK-RF as efficiently. CCK, originally believed to act as a hormone to directly stimulate enzyme secretion by acinar cells, may act through vagal afferent nerve endings, the CNS, and vagal efferent pathways. Synergism also exists between CCK and secretin in stimulating ductal and acinar secretion. (+) = upregulation/ stimulation (-) = downregulation/ inhibition |
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| Another loop involves circulating hormones. |
Nutrient molecules (glucose, amino acids, fatty acids) in the lower ileum, and proximal colon can inhibit CCK or meal-stimulated pancreatic secretion. This inhibition may be mediated by circulating hormones (such as PYY), or by vagal reflexes involving pancreatic polypeptide.
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| Frontiers of pancreatic physiology | You can judge that we have much to learn about pancreatic physiology. An emerging concept emphasizes the importance of the dorsal vagal complex with its sensory receptive area, its motor nucleus, and its area postrema whose fenestrated capillaries breach the blood-brain barrier. Signals from blood-borne hormones and nutrients can be integrated with nervous afferent impulses so that the motor vagal response is appropriate for the phase of digestion and absorption. | |
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Next Section (E): Regulation of Pancreatic Endocrine Function » |
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