GIT BRS PHYSIOLOGY PDF

Chapter 6 Gastrointestinal Physiology For additional ancillary materials related to this chapter, please visit thePoint. I. STRUCTURE AND INNERVATION OF THE GASTROINTESTINAL TRACT A. Structure of the gastrointestinal (GI) tract (Figure 6.1) FIGURE 6.1 Struc...

Chapter 6 Gastrointestinal Physiology For additional ancillary materials related to this chapter, please visit thePoint. I. STRUCTURE AND INNERVATION OF THE GASTROINTESTINAL TRACT A. Structure of the gastrointestinal (GI) tract (Figure 6.1) FIGURE 6.1 Structure of the gastrointestinal tract.  1. Epithelial cells are specialized in different parts of the GI tract for secretion or absorption. 2. Muscularis mucosa Contraction causes a change in the surface area for secretion or absorption. 3. Circular muscle Contraction causes a decrease in diameter of the lumen of the GI tract. 4. Longitudinal muscle Contraction causes shortening of a segment of the GI tract. 5. Submucosal plexus (Meissner plexus) and myenteric plexus comprise the enteric nervous system of the GI tract. integrate and coordinate the motility, secretory, and endocrine functions of the GI tract. B. Innervation of the GI tract The autonomic nervous system (ANS) of the GI tract comprises both extrinsic and intrinsic nervous systems. 1. Extrinsic innervation (parasympathetic and sympathetic nervous systems) Efferent fibers carry information from the brainstem and spinal cord to the GI tract. Afferent fibers carry sensory information from chemoreceptors and mechanoreceptors in the GI tract to the brainstem and spinal cord. a. Parasympathetic nervous system is usually excitatory on the functions of the GI tract. is carried via the vagus and pelvic nerves. Preganglionic parasympathetic fibers synapse in the myenteric and submucosal plexuses. Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 1. The vagus nerve innervates the esophagus, stomach, pancreas, and upper large intestine. Reflexes in which both afferent and efferent pathways are contained in the vagus nerve are called vagovagal reflexes.  2. The pelvic nerve innervates the lower large intestine, rectum, and anus. b. Sympathetic nervous system is usually inhibitory on the functions of the GI tract. Fibers originate in the spinal cord between T8 and L2. Preganglionic sympathetic cholinergic fibers synapse in the prevertebral ganglia. Postganglionic sympathetic adrenergic fibers leave the prevertebral ganglia and synapse in the myenteric and submucosal plexuses. Direct postganglionic adrenergic innervation of blood vessels and some smooth muscle cells also occurs. Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 2. Intrinsic innervation (enteric nervous system) coordinates and relays information from the parasympathetic and sympathetic nervous systems to the GI tract. uses local reflexes to relay information within the GI tract. controls most functions of the GI tract, especially motility and secretion, even in the absence of extrinsic innervation. a. Myenteric plexus (Auerbach plexus) primarily controls the motility of the GI smooth muscle. b. Submucosal plexus (Meissner plexus) primarily controls secretion and blood flow. receives sensory information from chemoreceptors and mechanoreceptors in the GI tract. II. REGULATORY SUBSTANCES IN THE GASTROINTESTINAL TRACT (FIGURE 6.2) FIGURE 6.2 Gastrointestinal hormones, paracrines, and neurocrines. A. GI hormones (Table 6.1) table 6.1 Summary of Gastrointestinal (GI) Hormones CCK = cholecystokinin; GIP = glucose-dependent insulinotropic peptide; GRP = gastrin-releasing peptide. are released from endocrine cells in the GI mucosa into the portal circulation, enter the general circulation, and have physiologic actions on target cells. Four substances meet the requirements to be considered “official” GI hormones; others are considered “candidate” hormones. The four official GI hormones are gastrin, cholecystokinin (CCK), secretin, and glucose-dependent insulinotropic peptide (GIP). 1. Gastrin contains 17 amino acids (“little gastrin”). Little gastrin is the form secreted in response to a meal. All of the biologic activity of gastrin resides in the four C-terminal amino acids. “Big gastrin” contains 34 amino acids, although it is not a dimer of little gastrin. a. Actions of gastrin 1. increases H+ secretion by the gastric parietal cells. 2. stimulates growth of gastric mucosa by stimulating the synthesis of RNA and new protein. Patients with gastrin-secreting tumors have hypertrophy and hyperplasia of the gastric mucosa. b. Stimuli for secretion of gastrin Gastrin is secreted from the G cells of the gastric antrum in response to a meal. Gastrin is secreted in response to the following: 1. small peptides and amino acids in the lumen of the stomach. The most potent stimuli for gastrin secretion are phenylalanine and tryptophan. 2. distention of the stomach. 3. vagal stimulation, mediated by gastrin-releasing peptide (GRP). Atropine does not block vagally mediated gastrin secretion because the mediator of the vagal effect is GRP, not acetylcholine (ACh). c. Inhibition of gastrin secretion H+ in the lumen of the stomach inhibits gastrin release. This negative feedback control ensures that gastrin secretion is inhibited if the stomach contents are sufficiently acidified. Somatostatin inhibits gastrin release. d. Zollinger–Ellison syndrome (gastrinoma) occurs when gastrin is secreted by non–β-cell tumors of the pancreas. 2. CCK contains 33 amino acids. is homologous to gastrin. The five C-terminal amino acids are the same in CCK and gastrin. The biologic activity of CCK resides in the C-terminal heptapeptide. Thus, the heptapeptide contains the sequence that is homologous to gastrin and has both CCK and gastrin activity. a. Actions of CCK 1. stimulates contraction of the gallbladder and simultaneously causes relaxation of the sphincter of Oddi for secretion of bile. 2. stimulates pancreatic enzyme secretion. 3. potentiates secretin-induced stimulation of pancreatic HCO3− secretion. 4. stimulates growth of the exocrine pancreas. 5. inhibits gastric emptying. Thus, meals containing fat stimulate the secretion of CCK, which slows gastric emptying to allow more time for intestinal digestion and absorption. b. Stimuli for the release of CCK CCK is released from the I cells of the duodenal and jejunal mucosa by 1. small peptides and amino acids. 2. fatty acids and monoglycerides. Triglycerides do not stimulate the release of CCK because they cannot cross intestinal cell membranes. 3. Secretin contains 27 amino acids. is homologous to glucagon; 14 of the 27 amino acids in secretin are the same as those in glucagon. All of the amino acids are required for biologic activity. a. Actions of secretin are coordinated to reduce the amount of H+ in the lumen of the small intestine. 1. stimulates pancreatic HCO3- secretion and increases growth of the exocrine pancreas. Pancreatic HCO3− neutralizes H+ in the intestinal lumen. 2. stimulates HCO3− and H2O secretion by the liver and increases bile production. 3. inhibits H+ secretion by gastric parietal cells. b. Stimuli for the release of secretin Secretin is released by the S cells of the duodenum in response to 1. H+ in the lumen of the duodenum. 2. fatty acids in the lumen of the duodenum. 4. GIP contain 42 amino acids. is homologous to secretin and glucagon. a. Actions of GIP 1. stimulates insulin release. In the presence of an oral glucose load, GIP causes the release of insulin from the pancreas. Thus, oral glucose is  more effective than intravenous glucose in causing insulin release and, therefore, glucose utilization. 2. inhibits H+ secretion by gastric parietal cells. b. Stimuli for the release of GIP GIP is secreted by the duodenum and jejunum. GIP is the only GI hormone that is released in response to fat, protein, and carbohydrate. GIP secretion is stimulated by fatty acids, amino acids, and orally administered glucose. 5. Candidate hormones are secreted by cells of the GI tract. Motilin increases GI motility and is involved in interdigestive myoelectric complexes. Pancreatic polypeptide inhibits pancreatic secretions. Glucagon-like peptide-1 (GLP-1) binds to pancreatic β-cells and stimulates insulin secretion. Analogues of GLP-1 may be helpful in the treatment of type 2 diabetes mellitus. Leptin decreases appetite. Ghrelin increases appetite. B. Paracrines are released from endocrine cells in the GI mucosa. diffuse over short distances to act on target cells located in the GI tract. The GI paracrines are somatostatin and histamine. 1. Somatostatin is secreted by cells throughout the GI tract in response to H+ in the lumen. Its secretion is inhibited by vagal stimulation. inhibits the release of all GI hormones. inhibits gastric H+ secretion. 2. Histamine is secreted by mast cells of the gastric mucosa. increases gastric H+ secretion directly and by potentiating the effects of gastrin and vagal stimulation. C. Neurocrines are synthesized in neurons of the GI tract, moved by axonal transport down the axons, and released by action potentials in the nerves.  Neurocrines then diffuse across the synaptic cleft to a target cell. The GI neurocrines are vasoactive intestinal peptide (VIP), neuropeptide Y, nitric oxide (NO), GRP (bombesin), and enkephalins. 1. VIP contains 28 amino acids and is homologous to secretin. is released from neurons in the mucosa and smooth muscle of the GI tract. produces relaxation of GI smooth muscle, including the lower esophageal sphincter. stimulates pancreatic HCO3- secretion and inhibits gastric H+ secretion. In these actions, it resembles secretin. is secreted by pancreatic islet cell tumors and is presumed to mediate pancreatic cholera. 2. GRP (bombesin) is released from vagus nerves that innervate the G cells. stimulates gastrin release from G cells. 3. Enkephalins (met-enkephalin and leu-enkephalin) are secreted from nerves in the mucosa and smooth muscle of the GI tract. stimulate contraction of GI smooth muscle, particularly the lower esophageal, pyloric, and ileocecal sphincters. inhibit intestinal secretion of fluid and electrolytes. This action forms the basis for the usefulness of opiates in the treatment of diarrhea. D. Satiety Hypothalamic centers 1. Satiety center (inhibits appetite) is located in the ventromedial nucleus of the hypothalamus. 2. Feeding center (stimulates appetite) is located in the lateral hypothalamic area of the hypothalamus. Anorexigenic neurons release proopiomelanocortin (POMC) in the hypothalamic centers and cause decreased appetite. Orexigenic neurons release neuropeptide Y in the hypothalamic centers and stimulate appetite. Leptin is secreted by fat cells. It stimulates anorexigenic neurons and  inhibits orexigenic neurons, thus decreasing appetite. Insulin and GLP-1 inhibit appetite. Ghrelin is secreted by gastric cells. It stimulates orexigenic neurons and inhibits anorexigenic neurons, thus increasing appetite. III. GASTROINTESTINAL MOTILITY Contractile tissue of the GI tract is almost exclusively unitary smooth muscle, with the exception of the pharynx, upper one-third of the esophagus, and external anal sphincter, all of which are striated muscle. Depolarization of circular muscle leads to contraction of a ring of smooth muscle and a decrease in diameter of that segment of the GI tract. Depolarization of longitudinal muscle leads to contraction in the longitudinal direction and a decrease in length of that segment of the GI tract. Phasic contractions occur in the esophagus, gastric antrum, and small intestine, which contract and relax periodically. Tonic contractions occur in the lower esophageal sphincter, orad stomach, and ileocecal and internal anal sphincters. A. Slow waves (Figure 6.3) FIGURE 6.3 Gastrointestinal slow waves superimposed by action potentials. Action potentials produce subsequent contraction. are oscillating membrane potentials inherent to the smooth muscle  cells of some parts of the GI tract. occur spontaneously. originate in the interstitial cells of Cajal, which serve as the pacemaker for GI smooth muscle. are not action potentials, although they determine the pattern of action potentials and, therefore, the pattern of contraction. 1. Mechanism of slow wave production is the cyclic opening of Ca2+ channels (depolarization) followed by opening of K+ channels (repolarization). Depolarization during each slow wave brings the membrane potential of smooth muscle cells closer to threshold and, therefore, increases the probability that action potentials will occur. Action potentials, produced on top of the background of slow waves, then initiate phasic contractions of the smooth muscle cells (see Chapter 1, VII B). 2. Frequency of slow waves varies along the GI tract, but is constant and characteristic for each part of the GI tract. is not influenced by neural or hormonal input. In contrast, the frequency of the action potentials that occur on top of the slow waves is modified by neural and hormonal influences. sets the maximum frequency of contractions for each part of the GI tract. is lowest in the stomach (3 slow waves/min) and highest in the duodenum (12 slow waves/min). B. Chewing, swallowing, and esophageal peristalsis 1. Chewing lubricates food by mixing it with saliva. decreases the size of food particles to facilitate swallowing and to begin the digestive process. 2. Swallowing The swallowing reflex is coordinated in the medulla. Fibers in the vagus and glossopharyngeal nerves carry information between the GI tract and the medulla. The following sequence of events is involved in swallowing: a. The nasopharynx closes and, at the same time, breathing is inhibited.  b. The laryngeal muscles contract to close the glottis and elevate the larynx. c. Peristalsis begins in the pharynx to propel the food bolus toward the esophagus. Simultaneously, the upper esophageal sphincter relaxes to permit the food bolus to enter the esophagus. 3. Esophageal motility The esophagus propels the swallowed food into the stomach. Sphincters at either end of the esophagus prevent air from entering the upper esophagus and gastric acid from entering the lower esophagus. Because the esophagus is located in the thorax, intraesophageal pressure equals thoracic pressure, which is lower than atmospheric pressure. In fact, a balloon catheter placed in the esophagus can be used to measure intrathoracic pressure. The following sequence of events occurs as food moves into and down the esophagus: a. As part of the swallowing reflex, the upper esophageal sphincter relaxes to permit swallowed food to enter the esophagus. b. The upper esophageal sphincter then contracts so that food will not reflux into the pharynx. c. A primary peristaltic contraction creates an area of high pressure behind the food bolus. The peristaltic contraction moves down the esophagus and propels the food bolus along. Gravity accelerates the movement. d. A secondary peristaltic contraction clears the esophagus of any remaining food. e. As the food bolus approaches the lower end of the esophagus, the lower esophageal sphincter relaxes. This relaxation is vagally mediated, and the neurotransmitter is VIP. f. The orad region of the stomach relaxes (“receptive relaxation”) to allow the food bolus to enter the stomach. 4. Clinical correlations of esophageal motility a. Gastroesophageal reflux (heartburn) may occur if the tone of the lower esophageal sphincter is decreased and gastric contents reflux into the esophagus. b. Achalasia may occur if the lower esophageal sphincter does not relax during swallowing, with impaired esophageal peristalsis. Food accumulates in the esophagus, and there is dilation of the esophagus  above the sphincter. C. Gastric motility The stomach has three layers of smooth muscle—the usual longitudinal and circular layers and a third oblique layer. The stomach has three anatomic divisions—the fundus, body, and antrum. The orad region of the stomach includes the fundus and the proximal body. This region contains oxyntic glands and is responsible for receiving the ingested meal. The caudad region of the stomach includes the antrum and the distal body. This region is responsible for the contractions that mix food and propel it into the duodenum. 1. “Receptive relaxation” is a vagovagal reflex that is initiated by distention of the stomach and is abolished by vagotomy. The orad region of the stomach relaxes to accommodate the ingested meal. CCK participates in “receptive relaxation” by increasing the distensibility of the orad stomach. 2. Mixing and digestion The caudad region of the stomach contracts to mix the food with gastric secretions and begins the process of digestion. The size of food particles is reduced. a. Slow waves in the caudad stomach occur at a frequency of 3 to 5 waves/min. They depolarize the smooth muscle cells. b. If threshold is reached during the slow waves, action potentials are fired, followed by contraction. Thus, the frequency of slow waves sets the maximal frequency of contraction. c. A wave of contraction closes the distal antrum. Thus, as the caudad stomach contracts, food is propelled back into the stomach to be mixed (retropulsion). d. Gastric contractions are increased by vagal stimulation and decreased by sympathetic stimulation. e. Even during fasting, contractions (the “migrating myoelectric complex”) occur at 90-minute intervals and clear the stomach of residual food. Motilin is the mediator of these contractions.  3. Gastric emptying The caudad region of the stomach contracts to propel food into the duodenum. a. The rate of gastric emptying is fastest when the stomach contents are isotonic. If the stomach contents are hypertonic or hypotonic, gastric emptying is slowed. b. Fat inhibits gastric emptying (i.e., increases gastric emptying time) by stimulating the release of CCK. c. H+ in the duodenum inhibits gastric emptying via direct neural reflexes. H+ receptors in the duodenum relay information to the gastric smooth muscle via interneurons in the GI plexuses. D. Small intestinal motility The small intestine functions in the digestion and absorption of nutrients. The small intestine mixes nutrients with digestive enzymes, exposes the digested nutrients to the absorptive mucosa, and then propels any nonabsorbed material to the large intestine. As in the stomach, slow waves set the basic electrical rhythm, which occurs at a frequency of 12 waves/min. Action potentials occur on top of the slow waves and lead to contractions. Parasympathetic stimulation increases intestinal smooth muscle contraction; sympathetic stimulation decreases it. 1. Segmentation contractions mix the intestinal contents. A section of small intestine contracts, sending the intestinal contents (chyme) in both orad and caudad directions. That section of small intestine then relaxes, and the contents move back into the segment. This back-and-forth movement produced by segmentation contractions causes mixing without any net forward movement of the chyme. 2. Peristaltic contractions are highly coordinated and propel the chyme through the small intestine toward the large intestine. Ideally, peristalsis occurs after digestion and absorption have taken place. Contraction behind the bolus and, simultaneously, relaxation in front of the bolus cause the chyme to be propelled caudally. The peristaltic reflex is coordinated by the enteric nervous system.  a. Food in the intestinal lumen is sensed by enterochromaffin cells, which release serotonin (5-hydroxytryptamine, 5-HT). b. 5-HT binds to receptors on intrinsic primary afferent neurons (IPANs), which initiate the peristaltic reflex. c. Behind the food bolus, excitatory transmitters cause contraction of circular muscle and inhibitory transmitters cause relaxation of longitudinal muscle. In front of the bolus, inhibitory transmitters cause relaxation of circular muscle and excitatory transmitters cause contraction of longitudinal muscle. 3. Gastroileal reflex is mediated by the extrinsic ANS and possibly by gastrin. The presence of food in the stomach triggers increased peristalsis in the ileum and relaxation of the ileocecal sphincter. As a result, the intestinal contents are delivered to the large intestine. E. Large intestinal motility Fecal material moves from the cecum to the colon (i.e., through the ascending, transverse, descending, and sigmoid colons), to the rectum, and then to the anal canal. Haustra, or saclike segments, appear after contractions of the large intestine. 1. Cecum and proximal colon When the proximal colon is distended with fecal material, the ileocecal sphincter contracts to prevent reflux into the ileum. a. Segmentation contractions in the proximal colon mix the contents and are responsible for the appearance of haustra. b. Mass movements occur 1 to 3 times/day and cause the colonic contents to move distally for long distances (e.g., from the transverse colon to the sigmoid colon). 2. Distal colon Because most colonic water absorption occurs in the proximal colon, fecal material in the distal colon becomes semisolid and moves slowly. Mass movements propel it into the rectum. 3. Rectum, anal canal, and defecation The sequence of events for defecation is as follows: a. As the rectum fills with fecal material, it contracts and the internal anal  sphincter relaxes (rectosphincteric reflex). b. Once the rectum is filled to about 25% of its capacity, there is an urge to defecate. However, defecation is prevented because the external anal sphincter is tonically contracted. c. When it is convenient to defecate, the external anal sphincter is relaxed voluntarily. The smooth muscle of the rectum contracts, forcing the feces out of the body. Intra-abdominal pressure is increased by expiring against a closed glottis (Valsalva maneuver). 4. Gastrocolic reflex The presence of food in the stomach increases the motility of the colon and increases the frequency of mass movements. a. The gastrocolic reflex has a rapid parasympathetic component that is initiated when the stomach is stretched by food. b. A slower, hormonal component is mediated by CCK and gastrin. 5. Disorders of large intestinal motility a. Emotional factors strongly influence large intestinal motility via the extrinsic ANS. Irritable bowel syndrome may occur during periods of stress and may result in constipation (increased segmentation contractions) or diarrhea (decreased segmentation contractions). b. Megacolon (Hirschsprung disease), the absence of the colonic enteric nervous system, results in constriction of the involved segment, marked dilation and accumulation of intestinal contents proximal to the constriction, and severe constipation. F. Vomiting A wave of reverse peristalsis begins in the small intestine, moving the GI contents in the orad direction. The gastric contents are eventually pushed into the esophagus. If the upper esophageal sphincter remains closed, retching occurs. If the pressure in the esophagus becomes high enough to open the upper esophageal sphincter, vomiting occurs. The vomiting center in the medulla is stimulated by tickling the back of the throat, gastric distention, and vestibular stimulation (motion sickness). The chemoreceptor trigger zone in the fourth ventricle is activated by  emetics, radiation, and vestibular stimulation. IV. GASTROINTESTINAL SECRETION (TABLE 6.2) table 6.2 Summary of Gastrointestinal (GI) Secretions CCK = cholecystokinin; GIP = glucose-dependent insulinotropic peptide. A. Salivary secretion 1. Functions of saliva a. initial starch digestion by α-amylase (ptyalin) and initial triglyceride  digestion by lingual lipase. b. lubrication of ingested food by mucus. c. protection of the mouth and esophagus by dilution and buffering of ingested foods. 2. Composition of saliva a. Saliva is characterized by 1. high volume (relative to the small size of the salivary glands). 2. high K+ and HCO3− concentrations. 3. low Na+ and Cl− concentrations. 4. hypotonicity. 5. presence of α-amylase, lingual lipase, and kallikrein. b. The composition of saliva varies with the salivary flow rate (Figure 6.4). 1. At the lowest flow rates, saliva has the lowest osmolarity and lowest Na+, Cl−, and HCO3− concentrations but has the highest K+ concentration. 2. At the highest flow rates (up to 4 mL/min), the composition of saliva is closest to that of plasma. 3. Formation of saliva (Figure 6.5) Saliva is formed by three major glands—the parotid, submandibular, and sublingual glands. The structure of each gland is similar to a bunch of grapes. The acinus (the blind end of each duct) is lined with acinar cells and secretes an initial saliva. A branching duct system is lined with columnar epithelial cells, which modify the initial saliva. When saliva production is stimulated, myoepithelial cells, which line the acinus and initial ducts, contract and eject saliva into the mouth. a. The acinus produces an initial saliva with a composition similar to plasma. This initial saliva is isotonic and has the same Na+, K+, Cl−, and HCO3− concentrations as plasma. b. The ducts modify the initial saliva by the following processes: 1. The ducts reabsorb Na+ and Cl-; therefore, the concentrations of these ions are lower than their plasma concentrations. 2. The ducts secrete K+ and HCO3-; therefore, the concentrations of these ions are higher than their plasma concentrations. 3. Aldosterone acts on the ductal cells to increase the reabsorption of Na+ and the secretion of K+ (analogous to its actions on the renal distal tubule). 4. Saliva becomes hypotonic in the ducts because the ducts are relatively impermeable to water. Because more solute than water is reabsorbed by the ducts, the saliva becomes dilute relative to plasma. 5. The effect of flow rate on saliva composition is explained primarily by changes in the contact time available for reabsorption and secretion processes to occur in the ducts. Thus, at high flow rates, saliva is most like the initial secretion from the acinus; it has the highest Na+ and Cl− concentrations and the lowest K+ concentration. At low flow rates, saliva is least like the initial secretion from the acinus; it has the lowest Na+ and Cl− concentrations and the highest K+ concentration. The only ion that does not “fit” this contact time explanation is HCO3−; HCO3− secretion is selectively stimulated when saliva secretion is stimulated. 4. Regulation of saliva production (Figure 6.6) Saliva production is controlled by the parasympathetic and sympathetic nervous systems (not by GI hormones). Saliva production is unique in that it is increased by both parasympathetic and sympathetic activity. Parasympathetic activity is more important, however. a. Parasympathetic stimulation (cranial nerves VII and IX) increases saliva production by increasing transport processes in the acinar and ductal cells and by causing vasodilation. Cholinergic receptors on acinar and ductal cells are muscarinic. The second messenger is inositol 1,4,5-triphosphate (IP3) and increased intracellular [Ca2+]. Anticholinergic drugs (e.g., atropine) inhibit the production of saliva and cause dry mouth. b. Sympathetic stimulation increases the production of saliva and the growth of salivary glands, although the effects are smaller than those of parasympathetic  stimulation. Receptors on acinar and ductal cells are β-adrenergic. The second messenger is cyclic adenosine monophosphate (cAMP). c. Saliva production is increased (via activation of the parasympathetic nervous system) by food in the mouth, smells, conditioned reflexes, and nausea. is decreased (via inhibition of the parasympathetic nervous system) by sleep, dehydration, fear, and anticholinergic drugs. FIGURE 6.4 Composition of saliva as a function of salivary flow rate. FIGURE 6.5 Modification of saliva by ductal cells. FIGURE 6.6 Regulation of salivary secretion. ACh = acetylcholine; cAMP = cyclic adenosine monophosphate; IP3 = inositol 1,4,5- triphosphate; NE = norepinephrine. B. Gastric secretion 1. Gastric cell types and their secretions (Table 6.3 and Figure 6.7) Parietal cells, located in the body, secrete HCl and intrinsic factor. Chief cells, located in the body, secrete pepsinogen. G cells, located in the antrum, secrete gastrin. 2. Mechanism of gastric H+ secretion (Figure 6.8) Parietal cells secrete HCl into the lumen of the stomach and, concurrently, absorb HCO3- into the bloodstream as follows: a. In the parietal cells, CO2 and H2O are converted to H+ and HCO3−, catalyzed by carbonic anhydrase. b. H+ is secreted into the lumen of the stomach by the H+–K+ pump (H+, K+-ATPase). Cl− is secreted along with H+; thus, the secretion product of the parietal cells is HCl. The drug omeprazole (a “proton pump inhibitor”) inhibits the H+, K+- ATPase and blocks H+ secretion. c. The HCO3- produced in the cells is absorbed into the bloodstream in exchange for Cl− (Cl-–HCO3- exchange). As HCO3− is added to the venous blood, the pH of the blood increases (“alkaline tide”). (Eventually, this HCO3− will be secreted in pancreatic secretions to neutralize H+ in the small intestine.) If vomiting occurs, gastric H+ never arrives in the small intestine, there is no stimulus for pancreatic HCO3− secretion, and the arterial blood becomes alkaline (metabolic alkalosis). 3. Stimulation of gastric H+ secretion (Figure 6.9) a. Vagal stimulation increases H+ secretion by a direct pathway and an indirect pathway. In the direct path, the vagus nerve innervates parietal cells and stimulates H+ secretion directly. The neurotransmitter at these synapses is ACh, the receptor on the parietal cells is muscarinic (M3), and the second messengers for CCK are IP3 and increased intracellular [Ca2+]. In the indirect path, the vagus nerve innervates G cells and stimulates gastrin secretion, which then stimulates H+ secretion by an endocrine action. The neurotransmitter at these synapses is GRP (not ACh). Atropine, a cholinergic muscarinic antagonist, inhibits H+ secretion by blocking the direct pathway, which uses ACh as a neurotransmitter. However, atropine does not block H+ secretion completely because it does not inhibit the indirect pathway, which uses GRP as a neurotransmitter.  Vagotomy eliminates both direct and indirect pathways. b. Gastrin is released in response to eating a meal (small peptides, distention of the stomach, vagal stimulation). stimulates H+ secretion by interacting with the cholecystokininB (CCKB) receptor on the parietal cells. The second messenger for gastrin on the parietal cell is IP3/Ca2+. Gastrin also stimulates enterochromaffin-like (ECL) cells and histamine secretion, which stimulates H+ secretion (not shown in figure). c. Histamine is released from ECL cells in the gastric mucosa and diffuses to the nearby parietal cells. stimulates H+ secretion by activating H2 receptors on the parietal cell membrane. The H2 receptor is coupled to adenylyl cyclase via a Gs protein. The second messenger for histamine is cAMP. H2 receptor–blocking drugs, such as cimetidine, inhibit H+ secretion by blocking the stimulatory effect of histamine. d. Potentiating effects of ACh, histamine, and gastrin on H+ secretion Potentiation occurs when the response to simultaneous administration of two stimulants is greater than the sum of responses to either agent given alone. As a result, low concentrations of stimulants given together can produce maximal effects. Potentiation of gastric H+ secretion can be explained, in part, because each agent has a different mechanism of action on the parietal cell. 1. Histamine potentiates the actions of ACh and gastrin in stimulating H+ secretion. Thus, H2 receptor blockers (e.g., cimetidine) are particularly effective in treating ulcers because they block both the direct action of histamine on parietal cells and the potentiating effects of histamine on ACh and gastrin. 2. ACh potentiates the actions of histamine and gastrin in stimulating H+ secretion. Thus, muscarinic receptor blockers, such as atropine, block both the  direct action of ACh on parietal cells and the potentiating effects of ACh on histamine and gastrin. 4. Inhibition of gastric H+ secretion Negative feedback mechanisms inhibit the secretion of H+ by the parietal cells. a. Low pH (5, pepsin is denatured. Thus, in the intestine, as HCO3− is secreted in pancreatic fluids, duodenal pH increases and pepsin is inactivated. d. Pancreatic proteases  include trypsin, chymotrypsin, elastase, carboxypeptidase A, and carboxypeptidase B. are secreted in inactive forms that are activated in the small intestine as follows: 1. Trypsinogen is activated to trypsin by a brush border enzyme, enterokinase. 2. Trypsin then converts chymotrypsinogen, proelastase, and procarboxypeptidase A and B to their active forms. (Even trypsinogen is converted to more trypsin by trypsin!) 3. After their digestive work is complete, the pancreatic proteases degrade each other and are absorbed along with dietary proteins. 2. Absorption of proteins (Figure 6.14) Digestive products of protein can be absorbed as amino acids, dipeptides, and tripeptides (in contrast to carbohydrates, which can only be absorbed as monosaccharides). a. Free amino acids Na+-dependent amino acid cotransport occurs in the luminal membrane. It is analogous to the cotransporter for glucose and galactose. The amino acids are then transported from cell to blood by facilitated diffusion. There are four separate carriers for neutral, acidic, basic, and imino amino acids, respectively. b. Dipeptides and tripeptides are absorbed faster than free amino acids. H+-dependent cotransport of dipeptides and tripeptides also occurs in the luminal membrane. After the dipeptides and tripeptides are transported into the intestinal cells, cytoplasmic peptidases hydrolyze them to amino acids. The amino acids are then transported from cell to blood by facilitated diffusion. FIGURE 6.14 Mechanism of absorption of amino acids, dipeptides, and tripeptides by intestinal epithelial cells. C. Lipids 1. Digestion of lipids a. Stomach 1. In the stomach, mixing breaks lipids into droplets to increase the surface area for digestion by pancreatic enzymes. 2. Lingual lipases digest some of the ingested triglycerides to monoglycerides and fatty acids. However, most of the ingested lipids are digested in the intestine by pancreatic lipases. 3. CCK slows gastric emptying. Thus, delivery of lipids from the stomach to the duodenum is slowed to allow adequate time for digestion and absorption in the intestine. b. Small intestine 1. Bile acids emulsify lipids in the small intestine, increasing the surface area for digestion. 2. Pancreatic lipases hydrolyze lipids to fatty acids, monoglycerides, cholesterol, and lysolecithin. The enzymes are pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2. 3. The hydrophobic products of lipid digestion are solubilized in micelles by bile acids. 2. Absorption of lipids a. Micelles bring the products of lipid digestion into contact with the absorptive surface of the intestinal cells. Then, fatty acids, monoglycerides, and cholesterol diffuse across the luminal membrane into the cells. Glycerol is hydrophilic and is not contained in the micelles. b. In the intestinal cells, the products of lipid digestion are reesterified to triglycerides, cholesterol ester, and phospholipids and, with apoproteins, form chylomicrons. Lack of apoprotein B results in the inability to transport chylomicrons out of the intestinal cells and causes abetalipoproteinemia. c. Chylomicrons are transported out of the intestinal cells by exocytosis. Because chylomicrons are too large to enter the capillaries, they are transferred to lymph vessels and are added to the bloodstream via the thoracic duct. 3. Malabsorption of lipids—steatorrhea can be caused by any of the following: a. pancreatic disease (e.g., pancreatitis, cystic fibrosis), in which the pancreas cannot synthesize adequate amounts of the enzymes (e.g., pancreatic lipase) needed for lipid digestion. b. hypersecretion of gastrin, in which gastric H+ secretion is increased and the duodenal pH is decreased. Low duodenal pH inactivates pancreatic lipase. c. ileal resection, which leads to a depletion of the bile acid pool because the bile acids do not recirculate to the liver. d. bacterial overgrowth, which may lead to deconjugation of bile acids and their “early” absorption in the upper small intestine. In this case, bile acids are not present throughout the small intestine to aid in lipid absorption. e. decreased number of intestinal cells for lipid absorption (tropical sprue). f. failure to synthesize apoprotein B, which leads to the inability to form chylomicrons. D. Absorption and secretion of electrolytes and H2O Electrolytes and H2O may cross intestinal epithelial cells by either cellular or paracellular (between cells) routes. Tight junctions attach the epithelial cells to one another at the luminal membrane. The permeability of the tight junctions varies with the type of epithelium. A “tight” (impermeable) epithelium is the colon. “Leaky” (permeable) epithelia are the small intestine and gallbladder. 1. Absorption of NaCl a. Na+ moves into the intestinal cells, across the luminal membrane, and down its electrochemical gradient by the following mechanisms: 1. passive diffusion (through Na+ channels). 2. Na+–glucose or Na+–amino acid cotransport. 3. Na+–Cl− cotransport. 4. Na+–H+ exchange. In the small intestine, Na+–glucose cotransport, Na+–amino acid cotransport, and Na+–H+ exchange mechanisms are most important. These cotransport and exchange mechanisms are similar to those in the renal proximal tubule. In the colon, passive diffusion via Na+ channels is most important. The Na+ channels of the colon are similar to those in the renal distal tubule and collecting ducts and are stimulated by aldosterone. b. Na+ is pumped out of the cell against its electrochemical gradient by the Na+–K+ pump in the basolateral membranes. c. Cl− absorption accompanies Na+ absorption throughout the GI tract by the following mechanisms: 1. passive diffusion by a paracellular route. 2. Na+–Cl− cotransport. 3. Cl−–HCO3− exchange. 2. Absorption and secretion of K+ a. Dietary K+ is absorbed in the small intestine by passive diffusion via a paracellular route. b. K+ is actively secreted in the colon by a mechanism similar to that for  K+ secretion in the renal distal tubule. As in the distal tubule, K+ secretion in the colon is stimulated by aldosterone. In diarrhea, K+ secretion by the colon is increased because of a flow rate–dependent mechanism similar to that in the renal distal tubule. Excessive loss of K+ in diarrheal fluid causes hypokalemia. 3. Absorption of H2O is secondary to solute absorption. is isosmotic in the small intestine and gallbladder. The mechanism for coupling solute and water absorption in these epithelia is the same as that in the renal proximal tubule. In the colon, H2O permeability is much lower than in the small intestine, and feces may be hypertonic. 4. Secretion of electrolytes and H2O by the intestine The GI tract also secretes electrolytes from blood to lumen. The secretory mechanisms are located in the crypts. The absorptive mechanisms are located in the villi. a. Cl- is the primary ion secreted into the intestinal lumen. It is transported through Cl− channels in the luminal membrane that are regulated by cAMP. b. Na+ is secreted into the lumen by passively following Cl−. H2O follows NaCl to maintain isosmotic conditions. c. Vibrio cholerae (cholera toxin) causes diarrhea by stimulating Cl− secretion. Cholera toxin catalyzes adenosine diphosphate (ADP) ribosylation of the αs subunit of the Gs protein coupled to adenylyl cyclase, permanently activating it. Intracellular cAMP increases; as a result, Cl- channels in the luminal membrane open. Na+ and H2O follow Cl− into the lumen and lead to secretory diarrhea. Some strains of Escherichia coli cause diarrhea by a similar mechanism. Oral rehydration solutions contain Na+, Cl−, HCO3−, and glucose. The inclusion of glucose stimulates absorption via Na+–glucose cotransport  to offset secretory losses. E. Absorption of other substances 1. Vitamins a. Fat-soluble vitamins (A, D, E, and K) are incorporated into micelles and absorbed along with other lipids. b. Most water-soluble vitamins are absorbed by Na+-dependent cotransport mechanisms. c. Vitamin B12 is absorbed in the ileum and requires intrinsic factor. The vitamin B12–intrinsic factor complex binds to a receptor on the ileal cells and is absorbed. Gastrectomy results in the loss of gastric parietal cells, which are the source of intrinsic factor. Injection of vitamin B12 is required to prevent pernicious anemia. Ileectomy results in loss of absorption of the vitamin B12–intrinsic factor complex and thus requires injection of vitamin B12. 2. Calcium absorption in the small intestine depends on the presence of adequate amounts of the active form of vitamin D, 1,25- dihydroxycholecalciferol, which is produced in the kidney. 1,25- Dihydroxycholecalciferol induces the synthesis of an intestinal Ca2+- binding protein, calbindin D-28K. Vitamin D deficiency or chronic renal failure results in inadequate intestinal Ca2+ absorption, causing rickets in children and osteomalacia in adults. 3. Iron is absorbed as heme iron (iron bound to hemoglobin or myoglobin) or as free Fe2+. In the intestinal cells, “heme iron” is degraded and free Fe2+ is released. The free Fe2+ binds to apoferritin and is transported into the blood. Free Fe2+ circulates in the blood bound to transferrin, which transports it from the small intestine to its storage sites in the liver and from the liver to the bone marrow for the synthesis of hemoglobin. Iron deficiency is the most common cause of anemia. VI. LIVER PHYSIOLOGY A. Bile formation and secretion (see IV D) B. Bilirubin production and excretion (Figure 6.15) FIGURE 6.15 Bilirubin metabolism. UDP = uridine diphosphate. Hemoglobin is degraded to bilirubin by the reticuloendothelial system. Bilirubin is carried in the circulation bound to albumin. In the liver, bilirubin is conjugated with glucuronic acid via the enzyme UDP glucuronyl transferase. A portion of conjugated bilirubin is excreted in the urine, and a portion is secreted into bile. In the intestine, conjugated bilirubin is converted to urobilinogen, which is returned to the liver via the enterohepatic circulation, and urobilin and stercobilin, which are excreted in feces. C. Metabolic functions of the liver 1. Carbohydrate metabolism performs gluconeogenesis, stores glucose as glycogen, and releases stored glucose into the circulation. 2. Protein metabolism synthesizes nonessential amino acids. synthesizes plasma proteins. 3. Lipid metabolism participates in fatty acid oxidation. synthesizes lipoproteins, cholesterol, and phospholipids. D. Detoxification Potentially toxic substances are presented to the liver via the portal circulation. The liver modifies these substances in “first-pass metabolism.” Phase I reactions are catalyzed by cytochrome P-450 enzymes, which are followed by phase II reactions that conjugate the substances. REVIEW TEST 1. Which of the following substances is released from neurons in the GI tract and produces smooth muscle relaxation? (A) Secretin (B) Gastrin (C) Cholecystokinin (CCK) (D) Vasoactive intestinal peptide (VIP) (E) Gastric inhibitory peptide (GIP) 2. Which of the following is the site of secretion of intrinsic factor? (A) Gastric antrum (B) Gastric fundus (C) Duodenum (D) Ileum (E) Colon 3. Vibrio cholerae causes diarrhea because it (A) increases HCO3− secretory channels in intestinal epithelial cells (B) increases Cl− secretory channels in crypt cells (C) prevents the absorption of glucose and causes water to be retained in the intestinal lumen isosmotically (D) inhibits cyclic adenosine monophosphate (cAMP) production in intestinal epithelial cells (E) inhibits inositol 1,4,5-triphosphate (IP3) production in intestinal epithelial cells 4. Cholecystokinin (CCK) has some gastrin-like properties because both CCK and gastrin (A) are released from G cells in the stomach (B) are released from I cells in the duodenum (C) are members of the secretin-homologous family (D) have five identical C-terminal amino acids (E) have 90% homology of their amino acids 5. Which of the following is transported in intestinal epithelial cells by a Na+- dependent cotransport process? (A) Fatty acids (B) Triglycerides (C) Fructose (D) Alanine (E) Oligopeptides  6. A 49-year-old male patient with severe Crohn disease has been unresponsive to drug therapy and undergoes ileal resection. After the surgery, he will have steatorrhea because (A) the liver bile acid pool increases (B) chylomicrons do not form in the intestinal lumen (C) micelles do not form in the intestinal lumen (D) dietary triglycerides cannot be digested (E) the pancreas does not secrete lipase 7. Cholecystokinin (CCK) inhibits (A) gastric emptying (B) pancreatic HCO3− secretion (C) pancreatic enzyme secretion (D) contraction of the gallbladder (E) relaxation of the sphincter of Oddi 8. Which of the following abolishes “receptive relaxation” of the stomach? (A) Parasympathetic stimulation (B) Sympathetic stimulation (C) Vagotomy (D) Administration of gastrin (E) Administration of vasoactive intestinal peptide (VIP) (F) Administration of cholecystokinin (CCK) 9. Secretion of which of the following substances is inhibited by low pH? (A) Secretin (B) Gastrin (C) Cholecystokinin (CCK) (D) Vasoactive intestinal peptide (VIP) (E) Gastric inhibitory peptide (GIP) 10. Which of the following is the site of secretion of gastrin? (A) Gastric antrum (B) Gastric fundus (C) Duodenum (D) Ileum (E) Colon 11. Micelle formation is necessary for the intestinal absorption of (A) glycerol (B) galactose (C) leucine (D) bile acids (E) vitamin B12 (F) vitamin D 12. Which of the following changes occurs during defecation? (A) Internal anal sphincter is relaxed (B) External anal sphincter is contracted (C) Rectal smooth muscle is relaxed (D) Intra-abdominal pressure is lower than when at rest (E) Segmentation contractions predominate 13. Which of the following is characteristic of saliva? (A) Hypotonicity relative to plasma (B) A lower HCO3− concentration than plasma (C) The presence of proteases (D) Secretion rate that is increased by vagotomy (E) Modification by the salivary ductal cells involves reabsorption of K+ and HCO3− 14. Which of the following substances is secreted in response to an oral glucose load? (A) Secretin (B) Gastrin (C) Cholecystokinin (CCK) (D) Vasoactive intestinal peptide (VIP) (E) Glucose-dependent insulinotropic peptide (GIP) 15. Which of the following is true about the secretion from the exocrine pancreas? (A) It has a higher Cl− concentration than does plasma (B) It is stimulated by the presence of HCO3− in the duodenum (C) Pancreatic HCO3− secretion is increased by gastrin (D) Pancreatic enzyme secretion is increased by cholecystokinin (CCK) (E) It is hypotonic  16. Which of the following substances must be further digested before it can be absorbed by specific carriers in intestinal cells? (A) Fructose (B) Sucrose (C) Alanine (D) Dipeptides (E) Tripeptides 17. Slow waves in small intestinal smooth muscle cells are (A) action potentials (B) phasic contractions (C) tonic contractions (D) oscillating resting membrane potentials (E) oscillating release of cholecystokinin (CCK) 18. A 24-year-old male graduate student participates in a clinical research study on intestinal motility. Peristalsis of the small intestine (A) mixes the food bolus (B) is coordinated by the central nervous system (CNS) (C) involves contraction of circular smooth muscle behind and in front of the food bolus (D) involves contraction of circular smooth muscle behind the food bolus and relaxation of circular smooth muscle in front of the bolus (E) involves relaxation of circular and longitudinal smooth muscle simultaneously throughout the small intestine 19. A 38-year-old male patient with a duodenal ulcer is treated successfully with the drug cimetidine. The basis for cimetidine’s inhibition of gastric H+ secretion is that it (A) blocks muscarinic receptors on parietal cells (B) blocks H2 receptors on parietal cells (C) increases intracellular cyclic adenosine monophosphate (cAMP) levels (D) blocks H+,K+-adenosine triphosphatase (ATPase) (E) enhances the action of acetylcholine (ACh) on parietal cells 20. Which of the following substances inhibits gastric emptying? (A) Secretin (B) Gastrin (C) Cholecystokinin (CCK) (D) Vasoactive intestinal peptide (VIP) (E) Gastric inhibitory peptide (GIP) 21. When parietal cells are stimulated, they secrete (A) HCl and intrinsic factor (B) HCl and pepsinogen (C) HCl and HCO3− (D) HCO3− and intrinsic factor (E) mucus and pepsinogen 22. A 44-year-old woman is diagnosed with Zollinger–Ellison syndrome. Which of the following findings is consistent with the diagnosis? (A) Decreased serum gastrin levels (B) Increased serum insulin levels (C) Increased absorption of dietary lipids (D) Decreased parietal cell mass (E) Peptic ulcer disease 23. Which of the following is the site of Na+–bile acid cotransport? (A) Gastric antrum (B) Gastric fundus (C) Duodenum (D) Ileum (E) Colon Answers and Explanations 1. The answer is D [II C 1]. Vasoactive intestinal peptide (VIP) is a gastrointestinal (GI) neurocrine that causes relaxation of GI smooth muscle. For example, VIP mediates the relaxation response of the lower esophageal sphincter when a bolus of food approaches it, allowing passage of the bolus into the stomach. 2. The answer is B [IV B 1; Table 6.3; Figure 6.7]. Intrinsic factor is secreted by the parietal cells of the gastric fundus (as is HCl). It is absorbed, with vitamin B12, in the ileum. 3. The answer is B [V D 4 c]. Cholera toxin activates adenylate cyclase and increases cyclic adenosine monophosphate (cAMP) in the intestinal crypt cells. In the crypt cells, cAMP activates the Cl−-secretory channels and produces a primary secretion of Cl− with Na+ and H2O following. 4. The answer is D [II A 2]. The two hormones have five identical amino acids at the C-terminus. Biologic activity of cholecystokinin (CCK) is associated with the seven C-terminal amino acids, and biologic activity of gastrin is associated with the four C-terminal amino acids. Because this CCK heptapeptide contains the five common amino acids, it is logical that CCK should have some gastrin- like properties. G cells secrete gastrin. I cells secrete CCK. The secretin family includes glucagon. 5. The answer is D [V A–C; Table 6.4]. Fructose is the only monosaccharide that is not absorbed by Na+-dependent cotransport; it is transported by facilitated diffusion. Amino acids are absorbed by Na+-dependent cotransport, but oligopeptides (larger peptide units) are not. Triglycerides are not absorbed without further digestion. The products of lipid digestion, such as fatty acids, are absorbed by simple diffusion. 6. The answer is C [IV D 4]. Ileal resection removes the portion of the small intestine that normally transports bile acids from the lumen of the gut and recirculates them to the liver. Because this process maintains the bile acid pool, new synthesis of bile acids is needed only to replace those bile acids that are lost in the feces. With ileal resection, most of the bile acids secreted are excreted in the feces, and the liver pool is significantly diminished. Bile acids are needed for micelle formation in the intestinal lumen to solubilize the products of lipid digestion so that they can be absorbed. Chylomicrons are formed within the intestinal epithelial cells and are transported to lymph vessels. 7. The answer is A [II A 2 a; Table 6.1]. Cholecystokinin (CCK) inhibits gastric emptying and therefore helps to slow the delivery of food from the stomach to the intestine during periods of high digestive activity. CCK stimulates both functions of the exocrine pancreas—HCO3− secretion and digestive enzyme secretion. It also stimulates the delivery of bile from the gallbladder to the small intestinal lumen by causing contraction of the gallbladder while relaxing the sphincter of Oddi. 8. The answer is C [III C 1]. “Receptive relaxation” of the orad region of the stomach is initiated when food enters the stomach from the esophagus. This parasympathetic (vagovagal) reflex is abolished by vagotomy. 9. The answer is B [II A 1; Table 6.1]. Gastrin’s principal physiologic action is to increase H+ secretion. H+ secretion decreases the pH of the stomach contents. The decreased pH, in turn, inhibits further secretion of gastrin—a classic example of negative feedback. 10. The answer is A [II A 1 b; Table 6.3; Figure 6.7]. Gastrin is secreted by the G cells of the gastric antrum. HCl and intrinsic factor are secreted by the fundus. 11. The answer is F [V E 1; Table 6.4]. Micelles provide a mechanism for solubilizing fat-soluble nutrients in the aqueous solution of the intestinal lumen until the nutrients can be brought into contact with and absorbed by the intestinal epithelial cells. Because vitamin D is fat soluble, it is absorbed in the same way as other dietary lipids. Glycerol is one product of lipid digestion that is water soluble and is not included in micelles. Galactose and leucine are absorbed by Na+-dependent cotransport. Although bile acids are a key ingredient of micelles, they are absorbed by a specific Na+-dependent cotransporter in the ileum. Vitamin B12 is water soluble; thus, its absorption does not require micelles. 12. The answer is A [III E 3]. Both the internal and external anal sphincters must be relaxed to allow feces to be expelled from the body. Rectal smooth muscle contracts and intra-abdominal pressure is elevated by expiring against a closed glottis (Valsalva maneuver). Segmentation contractions are prominent in the small intestine during digestion and absorption. 13. The answer is A [IV A 2 a; Table 6.2]. Saliva is characterized by hypotonicity and a high HCO3− concentration (relative to plasma) and by the presence of α-amylase and lingual lipase (not proteases). The high HCO3− concentration is achieved by secretion of HCO3− into saliva by the ductal cells (not reabsorption of HCO3−). Because control of saliva production is parasympathetic, it is abolished by vagotomy. 14. The answer is E [II A 4; Table 6.4]. Glucose-dependent insulinotropic peptide (GIP) is the only gastrointestinal (GI) hormone that is released in response to all three categories of nutrients—fat, protein, and carbohydrate. Oral glucose releases GIP, which, in turn, causes the release of insulin from the endocrine pancreas. This action of GIP explains why oral glucose is more effective than intravenous glucose in releasing insulin. 15. The answer is D [II A 2, 3; Table 6.2]. The major anion in pancreatic secretions is HCO3− (which is found in higher concentration than in plasma), and the Cl− concentration is lower than in plasma. Pancreatic secretion is stimulated by the presence of fatty acids in the duodenum. Secretin (not gastrin) stimulates pancreatic HCO3− secretion, and cholecystokinin (CCK) stimulates pancreatic enzyme secretion. Pancreatic secretions are always isotonic, regardless of flow rate. 16. The answer is B [V A, B; Table 6.4]. Only monosaccharides can be absorbed by intestinal epithelial cells. Disaccharides, such as sucrose, must be digested to monosaccharides before they are absorbed. On the other hand, proteins are hydrolyzed to amino acids, dipeptides, or tripeptides, and all three forms are transported into intestinal cells for absorption. 17. The answer is D [III A; Figure 6.3]. Slow waves are oscillating resting membrane potentials of the gastrointestinal (GI) smooth muscle. The slow waves bring the membrane potential toward or to threshold, but are not themselves action potentials. If the membrane potential is brought to threshold by a slow wave, then action potentials occur, followed by contraction. 18. The answer is D [III D 2]. Peristalsis is contractile activity that is coordinated by the enteric nervous system (not the central nervous system [CNS]) and propels the intestinal contents forward. Normally, it takes place after sufficient mixing, digestion, and absorption have occurred. To propel the food bolus forward, the circular smooth muscle must simultaneously contract behind the bolus and relax in front of the bolus; at the same time, longitudinal smooth muscle relaxes (lengthens) behind the bolus and contracts (shortens) in front of the bolus. 19. The answer is B [IV B 3 c, d (1), 6]. Cimetidine is a reversible inhibitor of H2 receptors on parietal cells and blocks H+ secretion. Cyclic adenosine monophosphate (cAMP) (the second messenger for histamine) levels would be expected to decrease, not increase. Cimetidine also blocks the action of acetylcholine (ACh) to stimulate H+ secretion. Omeprazole blocks H+, K+- adenosine triphosphatase (ATPase) directly. 20. The answer is C [II A 2 a; Table 6.1]. Cholecystokinin (CCK) is the most important hormone for digestion and absorption of dietary fat. In addition to causing contraction of the gallbladder, it inhibits gastric emptying. As a result, chyme moves more slowly from the stomach to the small intestine, thus allowing more time for fat digestion and absorption. 21. The answer is A [IV B I; Table 6.3]. The gastric parietal cells secrete HCl and intrinsic factor. The chief cells secrete pepsinogen. 22. The answer is E [II A 1 d; V C 3 b]. Zollinger–Ellison syndrome (gastrinoma) is a tumor of the non–β-cell pancreas. The tumor secretes gastrin, which then circulates to the gastric parietal cells to produce increased H+ secretion, peptic ulcer, and parietal cell growth (trophic effect of gastrin). Because the tumor does not involve the pancreatic β-cells, insulin levels should be unaffected. Absorption of lipids is decreased (not increased) because increased H+ secretion decreases the pH of the intestinal lumen and inactivates pancreatic lipases. 23. The answer is D [IV D 4]. Bile salts are recirculated to the liver in the enterohepatic circulation via a Na+–bile acid cotransporter located in the ileum of the small intestine.