Porth's Essentials of Pathophysiology, 4e

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Structure and Function of the Gastrointestinal System

C h a p t e r 2 8

stomach. The primary function of gastrin is the stimula- tion of gastric acid secretion. Gastrin also has a trophic, or growth-producing, effect on the mucosa of the small intestine, colon, and acid-secreting area of the stomach. Removal of the tissue that produces gastrin results in atrophy of these structures. Ghrelin is a recently discov- ered peptide hormone produced by endocrine cells in the mucosal layer of the fundus of the stomach. It displays potent growth hormone–releasing activity and has a stimulatory effect on food intake and digestive function, while reducing energy expenditure. The isolation of this hormone has led to new insights into the gut–brain regu- lation of growth hormone secretion and energy balance. The intestine is the source of secretin, cholecystoki- nin, and incretin hormones. Secretin , which is secreted by S cells in the mucosa of the duodenum and jeju- num, inhibits gastric acid secretion. The entry of an acid chyme into the intestine stimulates the release of secretin, which inhibits the release of gastrin. Secretin also stimulates the pancreas to secrete large quantities of fluid with a high bicarbonate concentration and low chloride concentration. The primary function of cho- lecystokinin (CCK), secreted by I cells in the intestinal mucosa, is the stimulation of pancreatic enzyme secre- tion. It also potentiates the action of secretin, increasing the pancreatic bicarbonate response to low circulating levels of secretin; and regulates gallbladder contrac- tion and gastric emptying. CCK has also been shown to inhibit food intake and to be an important mediator for appetite and amount of food consumed during a meal. Several gut-derived hormones have been identified as having what is termed an incretin effect, meaning that they increase insulin release after an oral glucose load. This sug- gests that gut-derived factors can stimulate insulin secre- tion after a high-carbohydrate meal. The two hormones that account for about 90% of the incretin effect are glucagon-like peptide 1 (GLP-1), which is released from L cells in the distal small intestine, and glucose-dependent insulinotropic peptide (GIP), which is released by K cells in the upper small intestine (mainly the jejunum). Because increased levels of GLP-1 and GIP can lower blood glucose levels by augmenting insulin release in a glucose-depen- dent manner (i.e., at low blood glucose levels no further insulin is secreted, minimizing the risk of hypoglycemia), these hormones have been targeted as possible antidia- betic drugs. Moreover, GLP-1 can exert other metaboli- cally beneficial effects, including suppression of glucagon release, slowing of gastric emptying, augmenting glucose clearance, and decreasing appetite and body weight.

Digestion and Absorption in the Gastrointestinal Tract Digestion involves the dismantling of foods into their constituent parts, a process that requires hydrolysis, enzyme cleavage, and fat emulsification. Hydrolysis is the breakdown of a compound that involves a chemi- cal reaction with water. The importance of hydrolysis to digestion is evidenced by the amount of water (7 to 8 L) that is secreted into the GI tract daily. Enzyme cleavage requires the use of enzymes to cut substances into smaller components. Emulsification involves the breakdown of large globules of dietary fat into smaller particles. Absorption is the process of moving nutrients and other materials from the external environment in the lumen of the GI tract into the blood or lymph of the internal environment. Absorption is accomplished by active transport and diffusion. A number of substances require a specific carrier or transport system. For exam- ple, vitamin B 12 is not absorbed in the absence of intrin- sic factor, which is secreted by the parietal cells of the stomach. Transport of amino acids and glucose occurs mainly in the presence of sodium. Water is absorbed passively along an osmotic gradient. digestive enzymes, the GI tract produces and secretes hormones that act locally, then pass into the general circulation for distribution to more distant sites. Among the hormones produced by the GI tract are gastrin, ghrelin, secretin, cholecystokinin, and incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose- dependent insulinotropic polypeptide [GIP]). These hormones influence appetite, GI motility, enzyme activity, electrolyte levels, and the secretion and action of hormones such as growth hormone, insulin, and glucagon. ■■ The stomach, in addition to producing mucus, secretes hydrochloric acid (HCl); pepsinogen, which is converted to pepsin, which is important in protein metabolism; and intrinsic factor, which is involved in the absorption of vitamin B 12 . ■■ The cells of the small intestine, where most digestion and absorption of foods take place, produces a watery alkaline fluid that aids in the digestive process and surface enzymes that aid in the digestion and absorption of carbohydrates and proteins. Digestive and absorptive processes in the small intestine are aided by bile from the liver and enzymes from the pancreas. ■■ In addition to secreting fluids containing

SUMMARY CONCEPTS

■■ Secretory glands throughout the gastrointestinal tract serve two basic purposes: production of mucus to lubricate and protect its mucosal layer and secretion of fluids and enzymes to aid in the digestion and absorption of nutrients.