Structure and Functions The
gastrointestinal (GI) tract is a muscular tube about ten meters long. It includes the mouth, pharynx, esophagus, stomach, small and large intestines, and anus. The channel running through this tube is the lumen. Food travels through the GI tract to be broken down into molecules. These food molecules then pass through the lining of the GI tract into the bloodstream, a process called absorption. Waste material that is not absorbed is eliminated as feces.
Since digestion, absorption, and elimination occur in different regions of the GI tract, the contents must be pushed aborally, meaning away from the mouth. This occurs by means of peristaltic contractions, which begin with a localized, circumferential narrowing of the lumen. From outside the organ, it would look as if someone had put a tight, invisible ring around the tract, causing a constriction. This constriction sweeps along the digestive tract, pushing the contents aborally. Peristaltic contractions require four major components: the muscular wall of the GI tract, nerve cells in the walls of the GI tract, nervous connections with the brain, and a relay system in the brain. These work together so that the contractions are coordinated on all sides of the lumen and move in the proper direction.
Most of the GI tract is lined with smooth muscle, which is controlled by a part of the nervous system that does not require any conscious effort in order to function. The wall of the digestive tract contains two layers of muscle. The inner layer consists of several layers of muscle cells arranged concentrically. In the outer layer, the cells are arranged longitudinally. When the inner layer of cells is stimulated by nerves, it contracts, producing a narrowing of the lumen that pushes material aborally. When the outer layer of cells contracts, it shortens the long axis of the GI tract, causing an increase in the diameter of the lumen. This enlargement is especially important in the esophagus, which must sometimes accommodate large pieces of food.
There are two networks of nerve cells in the wall of the GI tract. The important network that affects peristalsis is called the myenteric plexus and is located between the circular and longitudinal layers of muscle cells. It contains nerve cells that receive impulses from nerves coming from the brain and transmit those impulses to the muscle cells. One of the functions of this plexus is to help ensure that peristaltic contractions occur in the proper direction. It also enables peristalsis to begin after local distension of the esophagus. If a large piece of food is stuck in the esophagus, peristaltic contractions begin pushing the food down into the stomach.
Nervous connections between the esophagus and the brain influence peristalsis. Some neurons carry sensory information from the esophagus to the brain; this information is important for the brain to be able to sense discomfort in the esophagus. Other neurons carry information from the brain to the esophagus that can modulate the contraction strength and speed of peristalsis. A relay system in the brain stem is involved in the process of swallowing and may also play a role in controlling peristalsis. It is not yet clear to what degree peristalsis is governed by the brain as opposed to the smooth muscle cells or the myenteric plexus.
Peristaltic contractions are measured by means of an instrument called a manometer, which can be advanced into organs such as the esophagus. It monitors increases in intraluminal pressure (pressure inside the GI tract) caused by contractions. A tracing is obtained that plots pressure versus time. Different tracings are obtained for different regions of the esophagus. Thus, in a recording of peristalsis, tracings of the proximal esophagus would show a transient increase in pressure, followed by an increase in pressure in the middle and then the lower esophagus.
Peristaltic contractions differ in the various regions of the GI tract and serve different purposes. In the esophagus, where peristalsis serves to propel food from the pharynx into the stomach, the main type of activity is called primary peristalsis. Initiated by swallowing, it propels material down toward the stomach. Primary peristaltic contractions can push a solid mass of food down the esophagus in about six seconds. With the aid of gravity, liquids do not need peristaltic contractions, as they can pour down the esophagus in one second. Between the lower end of the esophagus and the stomach is a narrowed region called the lower esophageal
sphincter (LES). This is an area of muscular circular fibers that normally keep the junction between the esophagus and stomach closed. When food or liquids reach the lower esophagus, the LES relaxes, allowing them to pass into the stomach.
There are two main motility patterns in the stomach and small intestine: fasting and fed patterns. In the fasting pattern, there are long periods of relaxation that alternate with periods of intense, repeated peristaltic contractions. These contraction waves migrate along the stomach toward the small intestine. When viewed on a manometry tracing, they are called migrating motor complexes (MMCs). In the fed pattern, the motility response varies depending on the content of the meal. Solid meals cause different effects in different parts of the stomach. The proximal stomach is mainly for storing food after eating and for emptying stomach contents. After eating solids, the proximal stomach relaxes to accommodate the food. Later, it slowly contracts, emptying the material toward the small intestine.
The functions of the distal stomach are mixing food with stomach acid and enzymes and mechanically grinding solids into smaller pieces. Solids and liquids are also propelled by peristaltic contractions toward the pylorus, a narrow region separating the stomach from the small intestine. Only material that is finely ground will pass into the small intestine. The small intestine is about five meters long and moves the material coming from the stomach, called chyme, toward the large intestine. During the transit of chyme through the small intestine, water and nutrients are absorbed. Enzymes digest the food particles in chyme down into minute particles, or molecules. These molecules are absorbed through the lining of the small intestine into the bloodstream. Wastes that cannot be digested and absorbed pass to the large intestine, where more fluid is absorbed, leaving a semisolid material called feces.
The motility pattern of the small intestine is similar to that of the stomach during fasting: intermittent periods of peristalsis push material down toward the large intestine. The purpose of this fasting peristaltic activity is to sweep cellular debris and bacteria toward the large intestine. Otherwise, bacteria may overgrow in the small intestine and cause diarrhea. During the fed pattern, there are no prolonged quiescent periods between groups of peristaltic contractions as there are in the fasting state. The function of the fed state is to make sure that the chyme is mixed well with digestive enzymes and that it has an opportunity to come into contact with the absorptive surface of the intestinal wall. As with the rest of the GI tract, small intestinal motility is subject to the brain’s control. If a person is placed in a dangerous situation, the brain will send signals to decrease intestinal motility, which will no longer be a priority.
In the large intestine, or colon, peristalsis slowly moves feces toward the rectum for elimination. The slow movement enables most of the water in the feces to be absorbed into the bloodstream. In the proximal large intestine, liquid feces are moved back and forth by contractions, eventually moving distally. In time, this material becomes more solid and moves intermittently toward the rectum. This intermittent peristalsis is called mass movement. It fluctuates during the day, increasing in frequency after meals. As the feces distend the rectum, a reflex occurs that stimulates passage of stool to the outside.
Disorders and Diseases Peristalsis may not always progress normally; it may be absent, too vigorous, or uncoordinated. An example of a disorder involving lack of peristalsis is achalasia, which means “failure to relax.” In this disease, the LES does not relax, thus impairing the passage of food into the stomach. Another characteristic of the disorder is aperistalsis, which is the absence of peristalsis of the esophagus. One common symptom of achalasia is dysphagia, which is a sensation of food sticking in the throat. Another symptom is regurgitation of undigested food during or just after eating, which often results in weight loss.
The cause of primary achalasia is unknown. Secondary achalasia may be due to infiltrating cancer, radiation damage, or other external factors; in Central and South America, the most common cause is Chagas disease, a parasitic infection. Achalasia is characterized by a reduction in ganglion cells, which are nerve cells that are normally present in the myenteric plexus of the esophagus. There may also be damage to the cell bodies of nerve cells in the brain that innervate the myenteric plexus. It may be that the damaged ganglion cells cause damage to the brain cells, or vice versa. A neural lesion in the LES can lead to a sphincter muscle that fails to relax appropriately, which in turn leads to obstruction of the passage of food. One result is that the esophageal body eventually becomes chronically dilated. Another factor leading to dilation of the esophagus is the loss of ganglion cells in the wall of its body, which results in the absence of peristalsis.
Achalasia usually begins during middle age. The predominant symptom is dysphagia in response to all solids and frequently liquids as well. Eating often causes chest discomfort to the point that people with achalasia lose weight because they avoid eating. Although regurgitation of undigested foods commonly occurs shortly after eating, it may occur hours later, especially when the patient lies down at night. Food contents may be regurgitated and inhaled, leading to nighttime coughing spells.
On manometry, the peristaltic waves normally seen after an act of swallowing are absent. Instead, there may be some low-pressure contractions appearing simultaneously in all parts of the esophagus. Their lack of orderly progression prevents the contractions from propelling food down the esophagus. The pressure in the lumen of the esophagus in the region of the LES may be elevated; often the LES is so tight that it is difficult to advance the manometry catheter through it. The LES also fails to relax normally after swallowing.
Treatment of achalasia rarely results in a return of peristalsis, but it may provide relief for the obstruction caused by a tight LES. Some drugs can relax the LES, but success with these is variable. Often, stretching of the LES with instruments called dilators is performed. The best dilator is a long instrument with an inflatable balloon at the tip. The dilator is advanced into the esophagus and through the LES. The balloon tip is positioned so that when the balloon is inflated, it stretches the LES. The LES needs to be stretched to the point of tearing the circular muscle in order to achieve a long-term reduction in LES pressure. This procedure is risky and may be complicated by the development of a large tear, creating a hole in the wall of the esophagus called a perforation.
Surgical cutting of the LES, called an esophagomyotomy, is more effective than dilation. The more reduction in LES tone that occurs, however, the more likely it is that the person will suffer from reflux of stomach acid. Although the stomach’s lining is normally resistant to the irritating effects of acid, the esophagus may become irritated when exposed to chronic acid reflux. A common symptom of this reflux is heartburn, which is a sensation of hot material rising into the esophagus.
An example of too-vigorous peristalsis is esophageal spasm. There are a few different manometric patterns to esophageal spasm, the most consistent being one of intense contractions of the esophagus that do not sweep along its length but occur at the same time at different regions of the esophagus. During manometry, the esophagi of those patients with spasms are often very sensitive to stimulation with certain drugs, resulting in increased strength, or amplitude, of the contractions. Not only is there an exaggerated motor response in esophageal spasm but there may be an abnormal sensory component to the disorder as well. For example, loud noises or stressful mental tasks may cause an increase in the amplitude of contraction waves. Esophageal spasms tend to occur in middle age. The most common symptom is intermittent dysphagia that is variable in severity. It is not progressive and does not result in weight loss.
Chest pain is a frequent complaint and may mimic that of a heart attack.
The diagnosis of esophageal spasm often requires manometry. Another useful diagnostic test is to attempt to re-create symptoms of spasm. For example, a drug known to cause smooth muscle contraction is administered. If symptoms similar to the presenting chest pain are re-created, then it is presumed that the pain was attributable to esophageal spasm. Various medications that relax smooth muscle have been used to treat these spasms, with moderate success. Once the medications are stopped, however, the symptoms recur.
Peristalsis requires both an intact myenteric plexus and well-coordinated connections with the central nervous system. Diabetics commonly suffer from neuropathy, a condition that damages various nerve cells in the body. This neuropathy is thought to be responsible for their various gastrointestinal motility disturbances. About 75 percent of diabetics can be shown to have esophageal peristaltic disturbances—up to one-third of diabetics suffer from dysphagia—although they are commonly not felt. Using manometry, an absence of coordinated peristaltic activity is usually found. Diabetics may have tertiary contractions, which are noncoordinated, nonpropulsive contractions of the wall of the esophagus.
Stomach, or gastric, motility is abnormal in about 25 percent of diabetics, resulting in disordered gastric emptying. Emptying of liquids may be normal, but emptying of solids is commonly delayed. There is commonly an absence of MMCs, which results in a decrease in the ability of the stomach to grind food. There may also be spasms of the distal stomach, causing obstructions of materials that would normally flow out of the stomach and into the small intestine. Another gastric disturbance is gastroparesis, a decreased ability of the stomach to propel food along, resulting in a sensation of fullness despite long periods of elapsed time between meals. Because of this, diabetics often have difficulty finishing an entire meal. They may also suffer from nausea, bloating, and vomiting after meals. Treatment of gastroparesis includes reduction of blood sugars if they are elevated. This may be accomplished by reducing food intake (if previously excessive) or increasing the dose of insulin. Medications called prokinetic drugs may increase gastric motor activity; examples of these drugs include metoclopramide, dromperidone, and cisapride.
The neuropathy suffered by diabetics may damage the nerves that normally stimulate intestinal reabsorption of fluid; this results in diarrhea, which affects 10 percent of diabetics. Other diabetics suffer from constipation, which may be caused by impaired peristaltic activity of the colon.
Perspective and Prospects In 1674, the first case of what was probably achalasia was reported by Sir Thomas Willis, who called the disorder “cardiospasm.” In 1937, F. C. Lendrum proposed that cardiospasm was attributable to incomplete relaxation of the LES, and he changed the condition’s name to achalasia.
Throughout the twentieth century, study of peristalsis advanced in leaps and bounds. In 1927, E. Jacobson reported on an association between esophageal spasm and strong emotion; gastroenterologists continue to note a correlation between spastic disorders of the GI tract and anxiety. In 1938, E. M. Jones reported an experimental reproduction of esophageal spastic pain by the inflation of small balloons in the esophagus. The development of esophageal manometric techniques advanced significantly in the 1970s. These techniques have allowed a much more thorough understanding of gastrointestinal motility, which enables the development of better drugs to alter it. Therapeutic advances in treating disorders such as achalasia have been made, most notably starting in the 1940s, when A. M. Olsen performed pneumatic dilations of the esophagus.
One of the most practical advances for disorders involving decreased peristalsis has been the development of prokinetic drugs, which increase gastrointestinal motility. Metoclopramide was the first to be developed and is still in use. Cisapride may prove to be effective, especially because its effects do not wear off with chronic use, as do those of metoclopramide.
Perhaps the most important area of research into gastrointestinal motility is the study of the signals for smooth muscle contraction, such as which chemicals (neurotransmitters) are released by the nerve endings where they join up with nerve cells in the myenteric plexus or with the smooth muscle cells. More than fifteen hormones and neurotransmitters are known to affect gastrointestinal motility. Once their specific functions are better understood, researchers can try to develop drugs that mimic their effects, depending on whether an increase or a decrease in motility is desired.
In the United States, some motility disorders are very prevalent, such as irritable bowel syndrome (IBS). This disorder involves symptoms such as abdominal distension, abdominal pain relieved by bowel movements, bowel movements that become more frequent during pain episodes, constipation, and loose stools. IBS accounts for almost as many working days lost to illness as the common cold. It is the most common cause for referral to a gastroenterologist, making up 20 to 50 percent of their referrals. Surveys in the general population have shown that approximately 15 percent of Americans have symptoms to justify a diagnosis of IBS.
Most disorders of peristalsis are not deadly, but they can cause much discomfort. With better understanding of the neurology of the gut, as well as the acceptance of a model for understanding the disorders that includes attention to psychological and sociological effects on the GI tract, medicine will be able to better decrease the suffering that occurs with these disorders.
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