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Physiology Gastrointestinal System Chapter 27 | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Contents : Introduction 4 General Patterns Of Motility Peristalsis 8 Segmentation & Mixing 14 Basic Electrical Activity & Regulation Of Motility 16 Migrating Motor Complex 22...

Physiology Gastrointestinal System Chapter 27 | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Contents : Introduction 4 General Patterns Of Motility Peristalsis 8 Segmentation & Mixing 14 Basic Electrical Activity & Regulation Of Motility 16 Migrating Motor Complex 22 Stomach 29 Gastric Motility & Emptying 31 Regulation Of Gastric Motility & Emptying 35 Gastrointestinal System | Gastrointestinal Motility Contents : Vomiting 43 Small Intestine 54 Intestinal Motility Colon 56 59 Motility Of The Colon 61 Transit Time In The Small Intestine & Colon 65 Chapter Summary 71 Gastrointestinal System | Gastrointestinal Motility Introduction: The digestive and absorptive functions of the gastrointestinal system outlined in the previous chapter depend on a variety of mechanisms that soften the food, propel it through the length of the gastrointestinal tract (Table), and mix it with bile from the gallbladder and digestive enzymes secreted by the salivary glands and pancreas. Gastrointestinal System | Gastrointestinal Motility Table: Mean lengths of various segments of the gastrointestinal tract as measured by intubation in living humans. Segment Length (cm) Pharynx, esophagus, and stomach 65 Duodenum 25 Jejunum and ileum 260 Colon 110 Gastrointestinal System | Gastrointestinal Motility Some of these mechanisms depend on intrinsic properties of the intestinal smooth muscle. Others involve the operation of reflexes involving the neurons intrinsic to the gut, reflexes involving the central nervous system (CNS), paracrine effects of chemical messengers, and gastrointestinal hormones. General Patterns Of Motility Gastrointestinal System | Gastrointestinal Motility General Patterns Of Motility: Peristalsis Peristalsis is a reflex response that is initiated when the gut wall is stretched by the contents of the lumen, and it occurs in all parts of the gastrointestinal tract from the esophagus to the rectum. The stretch initiates a circular contraction behind the stimulus and an area of relaxation in front of it (Figure). Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility The wave of contraction then moves in an oral-to-caudal direction, propelling the contents of the lumen forward at rates that vary from 2 to 25 cm/s. Peristaltic activity can be increased or decreased by the autonomic input to the gut, but its occurrence is independent of extrinsic innervation. Indeed, progression of the contents is not blocked by removal and resuture of a segment of intestine in its original position and is blocked only if the segment is reversed before it is sewn back into place. Gastrointestinal System | Gastrointestinal Motility Peristalsis is an excellent example of the integrated activity of the enteric nervous system. It appears that local stretch releases serotonin, which activates sensory neurons that activate the myenteric plexus. Cholinergic neurons passing in a retrograde direction in this plexus activate neurons that release substance P and acetylcholine, causing smooth muscle contraction behind the bolus. Gastrointestinal System | Gastrointestinal Motility At the same time, cholinergic neurons passing in an anterograde direction activate neurons that secrete NO and vasoactive intestinal polypeptide (VIP), producing the relaxation ahead of the stimulus. Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Segmentation & Mixing : When the meal is present, the enteric nervous system promotes a motility pattern that is related to peristalsis but is designed to retard the movement of the intestinal contents along the length of the intestinal tract to provide time for digestion and absorption (Figure). This motility pattern is known as segmentation, and it provides for ample mixing of the intestinal contents (known as chyme) with the digestive juices. Gastrointestinal System | Gastrointestinal Motility A segment of bowel contracts at both ends, and then a second contraction occurs in the center of the segment to force the chyme both backward and forward. Unlike peristalsis, therefore, retrograde movement of the chyme occurs routinely in the setting of segmentation. This mixing pattern persists for as long as nutrients remain in the lumen to be absorbed. It presumably reflects programmed activity of the bowel dictated by the enteric nervous system, and can occur independent of central input, although the latter can modulate it. Gastrointestinal System | Gastrointestinal Motility Basic Electrical Activity & Regulation Of Motility : Except in the esophagus and the proximal portion of the stomach, the smooth muscle of the gastrointestinal tract has spontaneous rhythmic fluctuations in membrane potential between about −65 and −45 mV. This basic electrical rhythm (BER) is initiated by the interstitial cells of Cajal, stellate mesenchymal pacemaker cells with smooth muscle-like features that send long multiply branched processes into the intestinal smooth muscle. Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility In the stomach and the small intestine, these cells are located in the outer circular muscle layer near the myenteric plexus; in the colon, they are at the submucosal border of the circular muscle layer. In the stomach and small intestine, there is a descending gradient in pacemaker frequency, and as in the heart, the pacemaker with the highest frequency usually dominates. The BER itself rarely causes muscle contraction, but spike potentials superimposed on the most depolarizing portions of the BER waves do increase muscle tension (Figure). Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility The depolarizing portion of each spike is due to Ca2+ influx, and the repolarizing portion is due to K+ efflux. Many polypeptides and neurotransmitters affect the BER. For example, acetylcholine increases the number of spikes and the tension of the smooth muscle, whereas epinephrine decreases the number of spikes and the tension. The rate of the BER is about 4/min in the stomach. It is about 12/min in the duodenum and falls to about 8/min in the distal ileum. Gastrointestinal System | Gastrointestinal Motility In the colon, the BER rate rises from about 2/min at the cecum to about 6/min at the sigmoid. The function of the BER is to coordinate peristaltic and other motor activity, such as setting the rhythm of segmentation; contractions can occur only during the depolarizing part of the waves. After vagotomy or transection of the stomach wall, for example, peristalsis in the stomach becomes irregular and chaotic. Migrating Motor Complex Gastrointestinal System | Gastrointestinal Motility Migrating Motor Complex: During fasting between periods of digestion, the pattern of electrical and motor activity in gastrointestinal smooth muscle becomes modified so that cycles of motor activity migrate from the stomach to the distal ileum. Each cycle, or migrating motor complex (MMC), starts with a quiescent period (phase I), continues with a period of irregular electrical and mechanical activity (phase II), and ends with a burst of regular activity (phase III) (Figure). Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility The MMCs are initiated by motilin. The circulating level of this hormone increases at intervals of approximately 100 min in the inter-digestive state, coordinated with the contractile phases of the MMC. The contractions migrate aborally at a rate of about 5 cm/min, and also occur at intervals of approximately 100 min. Gastric secretion, bile flow, and pancreatic secretion increase during each MMC. Gastrointestinal System | Gastrointestinal Motility They likely serve to clear the stomach and small intestine of luminal contents in preparation for the next meal. Conversely, when a meal is ingested, secretion of motilin is suppressed (ingestion of food suppresses motilin release via mechanisms that have not yet been elucidated), and the MMC is abolished, until digestion and absorption are complete. Gastrointestinal System | Gastrointestinal Motility Instead, there is a return to peristalsis and the other forms of BER and spike potentials during this time. The antibiotic erythromycin binds to motilin receptors, and derivatives of this compound may be of value in treating patients in whom gastrointestinal motility is decreased. Stomach Gastrointestinal System | Gastrointestinal Motility Stomach: Food is stored in the stomach; mixed with acid, mucus, and pepsin; and released at a controlled, steady rate into the duodenum. Gastrointestinal System | Gastrointestinal Motility Gastric Motility & Emptying : When food enters the stomach, the fundus and upper portion of the body relax and accommodate the food with little if any increase in pressure (receptive relaxation). Peristalsis then begins in the lower portion of the body, mixing and grinding the food and permitting small, semiliquid portions of it to pass through the pylorus and enter the duodenum. Receptive relaxation is, in part, vagally mediated and triggered by movement of the pharynx and esophagus. Intrinsic reflexes also lead to relaxation as the stomach wall is stretched. Gastrointestinal System | Gastrointestinal Motility Peristaltic waves controlled by the gastric BER begin soon thereafter and sweep toward the pylorus. The contraction of the distal stomach caused by each wave is sometimes called antral systole and can last up to 10 s. Waves occur 3–4 times per minute. In the regulation of gastric emptying, the antrum, pylorus, and upper duodenum apparently function as a unit. Gastrointestinal System | Gastrointestinal Motility Contraction of the antrum is followed by sequential contraction of the pyloric region and the duodenum. In the antrum, partial contraction ahead of the advancing gastric contents prevents solid masses from entering the duodenum, and they are mixed and crushed instead. The more liquid gastric contents are squirted a bit at a time into the small intestine. Gastrointestinal System | Gastrointestinal Motility Normally, regurgitation from the duodenum does not occur, because the contraction of the pyloric segment tends to persist slightly longer than that of the duodenum. The prevention of regurgitation may also be due to the stimulating action of cholecystokinin (CCK) and secretin on the pyloric sphincter. Gastrointestinal System | Gastrointestinal Motility Regulation Of Gastric Motility & Emptying: The rate at which the stomach empties into the duodenum depends on the type of food ingested. Food rich in carbohydrate leaves the stomach in a few hours. Protein rich food leaves more slowly, and emptying is slowest after a meal containing fat (Figure). Gastrointestinal System | Gastrointestinal Motility The rate of emptying also depends on the osmotic pressure of the material entering the duodenum. Hyperosmolality of the duodenal contents is sensed by “duodenal osmoreceptors” that initiate a decrease in gastric emptying, which is probably neural in origin. Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Fats, carbohydrates, and acid in the duodenum inhibit gastric acid and pepsin secretion and gastric motility via neural and hormonal mechanisms. The messenger involved is probably peptide YY. CCK has also been implicated as an inhibitor of gastric emptying (Clinical Box 27–2). Gastrointestinal System | Gastrointestinal Motility Clinical Box 27–2 : Consequences of Gastric Bypass Surgery Patients who are morbidly obese often undergo a surgical procedure in which the stomach is stapled so that most of it is bypassed, and thus the reservoir function of the stomach is lost. As a result, such patients must eat frequent small meals. Gastrointestinal System | Gastrointestinal Motility If larger meals are eaten, because of rapid absorption of glucose from the intestine and the resultant hyperglycemia and abrupt rise in insulin secretion, hypoglycemic symptoms sometimes develop about 2 h after meals in patients who have undergone gastrectomy. Weakness, dizziness, and sweating after meals, due in part to hypoglycemia, are part of the picture of the “dumping syndrome,” a distressing syndrome that develops in patients in whom portions of the stomach have been removed or the jejunum has been anastomosed to the stomach. Gastrointestinal System | Gastrointestinal Motility Another cause of the symptoms is rapid entry of hypertonic meals into the intestine; this provokes the movement of so much water into the gut that significant hypovolemia and hypotension are produced. Therapeutic Highlights: There are no treatments, per se, for the dumping syndrome, other than avoiding large meals, and particularly those with high concentrations of simple sugars. Indeed, its occurrence may account for the overall success of bypass surgery in reducing food intake, and thus obesity, in many patients who undergo this surgery. Gastrointestinal System | Gastrointestinal Motility Vomiting Gastrointestinal System | Gastrointestinal Motility Vomiting : Vomiting is an example of central regulation of gut motility functions. Vomiting starts with salivation and the sensation of nausea. Reverse peristalsis empties material from the upper part of the small intestine into the stomach. The glottis closes, preventing aspiration of vomitus into the trachea. The breath is held in mid inspiration. Gastrointestinal System | Gastrointestinal Motility The muscles of the abdominal wall contract, and because the chest is held in a fixed position, the contraction increases intraabdominal pressure. The lower esophageal sphincter and the esophagus relax, and the gastric contents are ejected. The “vomiting center” in the reticular formation of the medulla (Figure) consists of various scattered groups of neurons in this region that control the different components of the vomiting act. Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Irritation of the mucosa of the upper gastrointestinal tract is one trigger for vomiting. Impulses are relayed from the mucosa to the medulla over visceral afferent pathways in the sympathetic nerves and vagi. Other causes of vomiting can arise centrally. For example, afferents from the vestibular nuclei mediate the nausea and vomiting of motion sickness. Gastrointestinal System | Gastrointestinal Motility Other afferents presumably reach the vomiting control areas from the diencephalon and limbic system, because emetic responses to emotionally charged stimuli also occur. Thus, we speak of “nauseating smells” and “sickening sights.” Chemoreceptor cells in the medulla can also initiate vomiting when they are stimulated by certain circulating chemical agents. Gastrointestinal System | Gastrointestinal Motility The chemoreceptor trigger zone in which these cells are located (Figure) is in the area postrema, a V-shaped band of tissue on the lateral walls of the fourth ventricle near the obex. Lesions of the area postrema have little effect on the vomiting response to gastrointestinal irritation or motion sickness, but abolish the vomiting that follows injection of apomorphine and a number of other emetic drugs. Gastrointestinal System | Gastrointestinal Motility Gastrointestinal System | Gastrointestinal Motility Such lesions also decrease vomiting in uremia and radiation sickness, both of which may be associated with endogenous production of circulating emetic substances. Serotonin (5-HT) released from enterochromaffin cells in the small intestine appears to initiate impulses via 5-HT3 receptors that trigger vomiting. In addition, there are dopamine D2 receptors and 5-HT3 receptors in the area postrema and adjacent nucleus of the solitary tract. Gastrointestinal System | Gastrointestinal Motility 5-HT3 antagonists such as ondansetron and D2 antagonists such as chlorpromazine and haloperidol are effective antiemetic agents. Corticosteroids, cannabinoids, and benzodiazepines, alone or in combination with 5-HT3 and D2 antagonists, are also useful in treatment of the vomiting produced by chemotherapy. The mechanisms of action of corticosteroids and cannabinoids are unknown, whereas the benzodiazepines probably reduce the anxiety associated with chemotherapy. Small Intestine Gastrointestinal System | Gastrointestinal Motility Small Intestine: In the small intestine, the intestinal contents are mixed with the secretions of the mucosal cells and with pancreatic juice and bile. Gastrointestinal System | Gastrointestinal Motility Intestinal Motility: The MMCs that pass along the intestine at regular intervals in the fasting state and their replacement by peristaltic and other contractions controlled by the BER are described above. In the small intestine, there are an average of 12 BER cycles/min in the proximal jejunum, declining to 8/min in the distal ileum. There are three types of smooth muscle contractions: peristaltic waves, segmentation contractions, and tonic contractions. Gastrointestinal System | Gastrointestinal Motility Peristalsis is described above. It propels the intestinal contents (chyme) toward the large intestines. Segmentation contractions (Figure), move the chyme to and from and increase its exposure to the mucosal surface. These contractions are initiated by focal increases in Ca2+ influx with waves of increased Ca2+ concentration spreading from each focus. Gastrointestinal System | Gastrointestinal Motility Tonic contractions are relatively prolonged contractions that in effect isolate one segment of the intestine from another. Note that these last two types of contractions slow transit in the small intestine to the point that the transit time is actually longer in the fed than in the fasted state. This permits longer contact of the chyme with the enterocytes and fosters absorption Colon Gastrointestinal System | Gastrointestinal Motility Colon: The colon serves as a reservoir for the residues of meals that cannot be digested or absorbed. Motility in this segment is likewise slowed to allow the colon to absorb water, Na+, and other minerals. By removing about 90% of the fluid, it converts the 1000–2000 mL of isotonic chyme that enters it each day from the ileum to about 200–250 mL of semisolid feces. Gastrointestinal System | Gastrointestinal Motility Motility Of The Colon: The ileum is linked to the colon by a structure known as the ileocecal valve, which restricts reflux of colonic contents, and particularly the large numbers of commensal bacteria, into the relatively sterile ileum. The portion of the ileum containing the ileocecal valve projects slightly into the cecum, so that increases in colonic pressure squeeze it shut, whereas increases in ileal pressure open it. Gastrointestinal System | Gastrointestinal Motility It is normally closed. Each time a peristaltic wave reaches it, it opens briefly, permitting some of the ileal chyme to squirt into the cecum. When food leaves the stomach, the cecum relaxes and the passage of chyme through the ileocecal valve increases (gastroileal reflex). This is presumably a vago-vagal reflex. The movements of the colon include segmentation contractions and peristaltic waves like those occurring in the small intestine. Gastrointestinal System | Gastrointestinal Motility Segmentation contractions mix the contents of the colon and, by exposing more of the contents to the mucosa, facilitate absorption. Peristaltic waves propel the contents toward the rectum, although weak antiperistalsis is sometimes seen. A third type of contraction that occurs only in the colon is the mass action contraction, occurring about 10 times per day, in which there is simultaneous contraction of the smooth muscle over large confluent areas. Gastrointestinal System | Gastrointestinal Motility These contractions move material from one portion of the colon to another. They also move material into the rectum, and rectal distension initiates the defecation reflex (see below). The movements of the colon are coordinated by the BER of the colon. The frequency of this wave, unlike the wave in the small intestine, increases along the colon, from about 2/min at the ileocecal valve to 6/min at the sigmoid. Gastrointestinal System | Gastrointestinal Motility Transit Time In The Small Intestine & Colon: The first part of a test meal reaches the cecum in about 4 h in most individuals, and all the undigested portions have entered the colon in 8 or 9 h. On average, the first remnants of the meal traverse the first third of the colon in 6 h, the second third in 9h, and reach the terminal part of the colon (the sigmoid colon) in 12 h. From the sigmoid colon to the anus, transport is much slower (Clinical Box 27–5). Gastrointestinal System | Gastrointestinal Motility When small colored beads are fed with a meal, an average of 70% of them are recovered in the stool in 72 h, but total recovery requires more than a week. Transit time, pressure fluctuations, and changes in pH in the gastrointestinal tract can be observed by monitoring the progress of a small pill that contains sensors and a miniature radio transmitter. Gastrointestinal System | Gastrointestinal Motility CLINICAL BOX 27–5 Constipation Constipation refers to a pathologic decrease in bowel movements. It was previously considered to reflect changes in motility, but the recent success of a drug designed to enhance chloride secretion for the treatment of chronic constipation suggests alterations in the balance between secretion and absorption in the colon could also contribute to symptom generation. Gastrointestinal System | Gastrointestinal Motility Patients with persistent constipation, and particularly those with a recent change in bowel habits, should be examined carefully to rule out underlying organic disease. However, many normal humans defecate only once every 2–3 days, even though others defecate once a day and some as often as three times a day. Furthermore, the only symptoms caused by constipation are slight anorexia and mild abdominal discomfort and distension. Gastrointestinal System | Gastrointestinal Motility These symptoms are not due to absorption of “toxic substances,” because they are promptly relieved by evacuating the rectum and can be reproduced by distending the rectum with inert material. In western societies, the amount of misinformation and undue apprehension about constipation probably exceeds that about any other health topic. Symptoms other than those described above that are attributed by the lay public to constipation are due to anxiety or other causes. Gastrointestinal System | Gastrointestinal Motility Therapeutic Highlights Most cases of constipation are relieved by a change in the diet to include more fiber, or the use of laxatives that retain fluid in the colon, thereby increasing the bulk of the stool and promoting reflexes that lead to evacuation. As noted above, lubiprostone has recently joined the armamentarium for the treatment of constipation, and is assumed to act by enhancing chloride, and thus water, secretion into the colon thereby increasing the fluidity of the colonic contents. Chapter Summary Gastrointestinal System | Gastrointestinal Motility Chapter Summary: The regulatory factors that govern gastrointestinal secretion also regulate its motility to soften the food, mix it with secretions, and propel it along the length of the tract. Two major patterns of motility are peristalsis and segmentation, which serve to propel or retard/mix the luminal contents, respectively. Peristalsis involves coordinated contractions and relaxations above and below the food bolus. Gastrointestinal System | Gastrointestinal Motility The membrane potential of the majority of gastrointestinal smooth muscle undergoes rhythmic fluctuations that sweep along the length of the gut. The rhythm varies in different gut segments and is established by pacemaker cells known as interstitial cells of Cajal. This basic electrical rhythm (BER) provides for sites of muscle contraction when stimuli superimpose spike potentials on the depolarizing portion of the BER waves. Gastrointestinal System | Gastrointestinal Motility In the period between meals, the intestine is relatively quiescent, but every 90 min or so it is swept through by a large peristaltic wave triggered by the hormone motilin. This migrating motor complex presumably serves a “housekeeping” function. Swallowing is triggered centrally and is coordinated with a peristaltic wave along the length of the esophagus that drives the food bolus to the stomach, even against gravity. Gastrointestinal System | Gastrointestinal Motility Relaxation of the lower esophageal sphincter is timed to just precede the arrival of the bolus, thereby limiting reflux of the gastric contents. Nevertheless, gastroesophageal reflux disease is one of the most common gastrointestinal complaints. The stomach accommodates the meal by a process of receptive relaxation. This permits an increase in volume without a significant increase in pressure. The stomach then serves to mix the meal and to control its delivery to downstream segments. Gastrointestinal System | Gastrointestinal Motility Luminal contents move slowly through the colon, which enhances water recovery. Distension of the rectum causes reflex contraction of the internal anal sphincter and the desire to defecate. After toilet training, defecation can be delayed until a convenient time via voluntary contraction of the external anal sphincter.