Slow Waves of Electrical Depolarization Are a Unique Feature of Gut Smooth Muscle

The first level of control of GI motility lies in the intrinsic electrical properties of the smooth muscle mass. These electrical properties consist of spontaneously undulating waves of partial depolarization that sweep over the gut smooth muscle. The origin of this electrical activity is from specialized smooth muscle cells referred to as the interstitial cells of Cajal (ICC). The ICC form an interconnecting lattice of cells that surrounds the circular and longitudinal layers of muscle over the entire length of the gut. These cells are very similar in structure and function to the Purkinje cells of the heart. The ICC exhibit rhythmical and spontaneous oscillation in their transmembrane electrical potentials, as illustrated in Figure 28-1. They are connected to one another and to cells of the general smooth muscle mass by tight junctions or nexuses. These connections allow for the flow of ions from cell to cell. The resulting ionic movements lead to the propagation of waves of partial cell membrane depolarization across large numbers of cells. Within the ICC, fluctuations in intracellular calcium concentrations appear responsible for the spontaneous changes in membrane polarization. Figure 28-1 illustrates the concept of a fluctuating membrane potential in a single ICC. The property of spontaneous electrical rhythmicity, in combination with their electrical connection to the smooth muscle mass, imparts to the ICC their role as electrical “pacemakers” of the gut.

In GI smooth muscle cells, the baseline membrane potential is usually –70 to –60 millivolts (mV). Under the influence of the ICC, the membrane potential fluctuates from this baseline level by as much as 20 to 30 mV. Thus, under resting conditions, the depolarization is only partial, and the membrane potential never reaches 0 mV. The smooth muscle cells are connected to the ICC and to each other by nexuses, allowing the changes in membrane potential to be spread, or propagated, over large areas of muscle. The ICC initiate these changes and thus determine their origin and direction of propagation. Under normal conditions in the small intestine, changes in membrane potential begin high in the duodenum and are propagated aborally (away from the mouth) along the length of the small intestine (Figure 28-2). These aborally moving waves of partial depolarization are called slow waves or the basic electrical rhythm of the gut. In the dog, slow waves occur about 20 times per minute in the small intestine. In the stomach and colon, slow waves occur less frequently, about five times per minute. However, the slow waves are present throughout the smooth muscle portions of the GI tract. The frequency of slow waves varies among domestic species, but their presence does not vary.

The slow waves are an intrinsic property of the GI smooth muscle and associated ICC. The presence of the slow waves depends only on the ICC, whereas the amplitude and, to a lesser extent, the frequency of the slow waves can be modulated by the ENS. The link between slow waves and muscle contractions, however, is under control of nervous, endocrine, and paracrine factors, as discussed next.

When Slow Waves Reach Sensitized Smooth Muscle Cells, Action Potentials and Contraction Result

Slow waves have an important relationship with muscle contractions, but they are not the direct stimuli for contractions. Slow waves are constantly passing over GI smooth muscle, whether it is actively contracting or not. GI smooth muscle cells, as with other muscle cells, contract in association with action, or spike, potentials. These potentials are characterized by complete depolarization of the membrane for a short time, in contrast to the slow waves, which are characterized by incomplete depolarization (see Chapter 4). Action potentials in the GI smooth muscle occur only in association with slow waves. Thus the presence of slow waves is necessary but not sufficient to cause muscle contractions. When slow waves pass over an area of smooth muscle without eliciting action potentials, no contractions occur. When slow waves pass over an area of smooth muscle and action potentials are superimposed on the slow waves, gut muscle contracts. Control and coordination of smooth muscle activity is achieved by influencing the likelihood that action potentials will be superimposed on slow waves. Such control is a function of peptides and regulatory substances produced by the ENS and enteric endocrine and paracrine cells.

Smooth muscle control and coordination are achieved by modulation of the baseline electrical potential in the smooth muscle cells. Peptides and other regulatory molecules from ENS neurons or endocrine/paracrine cells are released in the vicinity of the smooth muscle cells, affecting membrane ion channels and influencing the baseline membrane potential (see Chapter 27 for a discussion of gut peptides and other regulatory molecules). Excitatory molecules elevate the baseline (bring it closer to zero), and inhibitory molecules lower the baseline (make it more negative). The position of the baseline influences how close the overall potential will come to 0 mV at the crest of a slow wave. When the membrane potential of a smooth muscle comes close to zero, action potentials occur and muscle contracts (Figure 28-3). Regulatory molecules (neurocrines, paracrines, and hormones) that are excitatory elicit smooth muscle contraction by elevating the baseline, whereas inhibitory substances inhibit muscle contraction by lowering the baseline.

The integrated actions of the slow waves, ENS, and endocrine/paracrine system appear to function to synchronize the contractions of the GI muscle mass. For the muscle to perform efficiently, all or many of the muscle cells in one layer of a segment of gut must be synchronized to contract simultaneously. This can best be visualized by considering the circular muscle layer. The contents of the circle cannot be “squeezed” effectively unless all the muscles of the circumference contract simultaneously; it would have little effect on luminal pressure if one portion of the circle contracted while another portion relaxed. In any discrete area of gut, slow waves pass simultaneously over the entire circumference of the smooth muscle. If that area has been sensitized by an excitatory regulatory molecule, the entire circumference of circular muscle will contract in synchrony.

Muscle contractions can occur at a frequency no higher than the frequency of the slow waves. As an example of frequency modulation, consider the activity of muscle in the stomach of the dog. Slow waves in the canine stomach occur about five times per minute. The crest of each slow wave may or may not be accompanied by action potentials. Therefore, during a given minute, the muscle in a localized area may not contract at all or may contract up to five times. If the passing slow waves generate no action potentials, the muscle does not contract at all. In a given minute, if action potentials are associated with one slow wave, the muscle contracts once. Action potentials on two slow waves result in two contractions, and so on, up to a maximum of five contractions per minute, but no more than five, because there are no more slow waves.

The motility patterns of the gut vary in their complexity, as described in the following sections. In the stomach and colon, motility patterns are relatively complex compared with the small intestine. In all cases, motility patterns are programmed into the ENS and coordinated in conjunction with the slow waves.

Coordinated Motility Enables the Lips, Tongue, Mouth, and Pharynx to Grasp Food and Propel It Down the Gastrointestinal Tract

Before digestion can begin, food must be directed into the GI tract. To ingest food, quadruped animals must first grasp it with the lips, teeth, or tongue. This involves highly coordinated activity of small, voluntary skeletal muscles. The muscles of the face, lips, and tongue appear to be among the most delicately controlled voluntary muscles of most domestic animals. The exact method of food prehension varies greatly among different species. For example, horses use their lips extensively, whereas cattle often use their tongues for grasping food. In all domestic animals, however, prehension is a highly coordinated process involving direct control by the central nervous system (CNS). Problems of prehension may develop because of abnormalities in the teeth, jaws, muscles of the tongue and face, cranial nerves, or CNS. The facial nerve, the glossopharyngeal nerve, and the motor branch of the trigeminal nerve control the muscles of prehension.

Mastication, or chewing, involves the actions of the jaws, tongue, and cheeks and is the first act of digestion. It serves not only to break food particles down to a size that will pass into the esophagus but also to moisten and lubricate food by thoroughly mixing it with saliva. Abnormalities of the teeth are a common cause of digestive disturbances in animals.

Deglutition, or swallowing, involves voluntary and involuntary stages and occurs after food has been well masticated. In the voluntary phase of swallowing, food is molded into a bolus by the tongue and then pushed back into the pharynx. When food enters the pharynx, sensory nerve endings detect its presence and initiate the involuntary portion of the swallow reflex.

The involuntary actions of the swallow reflex occur primarily within the pharynx and esophagus. The pharynx is the common opening of both the respiratory and the digestive tract. The major physiological function of the pharynx is to ensure that air, and only air, enters the respiratory tract and that food and water, and only food and water, enter the digestive tract. The involuntary portion of the swallow reflex is the action that directs food into the digestive system and away from the upper airway. This reflex involves the following series of highly coordinated actions (Figure 28-4). Breathing stops momentarily. The soft palate is elevated, closing the pharyngeal opening of the nasopharynx and preventing food from entering the internal openings of the nostrils. The tongue is pressed against the hard palate, closing off the oral opening of the pharynx. The hyoid bone and larynx are pulled forward; this action pulls the glottis under the epiglottis, blocking the laryngeal opening. Concurrently, the arytenoid cartilages constrict, further closing the opening of the larynx and preventing the movement of food into the respiratory system. When all openings to the pharynx are closed, a wave of muscular constriction passes over the walls of the pharynx, pushing the bolus of food toward the opening of the esophagus. As the food reaches the esophagus, the upper esophageal sphincter relaxes to accept the material.

The complex reactions of deglutition are controlled by lower motor neurons located in various centers of the brainstem. Efferent nerve fibers from these centers travel in the facial, vagus, hypoglossal, and glossopharyngeal nerves, as well as the motor branch of the trigeminal nerve. Clinically, problems with prehension, mastication, and deglutition frequently are related to neurological lesions, either peripherally in the cranial nerves or centrally in the brainstem.

Motility of the Esophagus Propels Food from the Pharynx to the Stomach

The esophagus, as with other tubular portions of the gut, contains an outer longitudinal and inner circular layer of muscle. The esophagus is unique compared with other areas of the gut in that much of its muscular wall is composed of striated skeletal muscle fibers. In most domestic animals the entire length of esophageal musculature is striated. In horses, primates, and cats, however, a portion of the distal esophagus is smooth muscle. The striated muscle portions of esophagus are under control of somatic (not parasympathetic) motor neurons in the vagus nerve, whereas the smooth muscle portions are under direct control of the ENS and indirect control of the autonomic nervous system. A myenteric plexus exists throughout the entire length of the esophagus. In the area of striated muscle, the myenteric plexus probably serves a sensory function and acts to coordinate the movements of the striated muscle portion with the esophageal smooth muscle segments and stomach.

In terms of motor activity, the esophagus may be viewed as consisting of an upper sphincter, body, and lower sphincter. The upper esophageal sphincter is called the cricopharyngeal muscle. This muscle and the upper end of the esophagus are attached to the cricoid cartilage of the larynx. When deglutition is not taking place, the muscle compresses the end of the esophagus against the cartilage of the larynx, tightly closing the upper esophageal opening. During deglutition the cricopharyngeal muscle relaxes and the larynx is pulled forward. The ventral portion of the upper end of the esophagus is attached to the larynx and the dorsal portion to the cervical spine. Because of these attachments, the forward motion of the larynx in conjunction with the relatively fixed nature of the cervical spine tends to pull open the upper esophageal orifice passively (see Figure 28-4).

The body of the esophagus serves as a relatively simple conduit, rapidly transferring food from the pharynx to the stomach. Food is propelled through the esophagus by propulsive movements known as peristalsis. Peristalsis consists of a moving ring of constriction in the wall of a tubular organ. In the esophagus, these rings start at the cranial end and progress toward the stomach. The rings reduce or obliterate the esophageal lumen, thus pushing the bolus of food ahead of them in much the same manner as a person would push material out of a soft rubber tube by stripping it with the fingers. In addition to the constriction of the circular muscles, there may be some contraction of longitudinal muscles just ahead of, or aboral to, the ring of circular muscle contraction. This longitudinal muscle activity increases the size of the esophageal lumen to accommodate the advancing food bolus (Figure 28-5). Peristalsis is a universal type of GI propulsive motility that exists at all levels of the gut.

During deglutition the upper esophageal sphincter relaxes as the pharynx constricts; food is pushed into the upper portion of the esophageal body, and a wave of peristalsis propels the material toward the stomach. As the food bolus reaches the distal end of the esophagus, the lower sphincter relaxes, and the ingested matter enters the stomach. If the esophagus is not cleared of food material by the primary wave of peristalsis, secondary peristaltic waves are generated. One or more secondary waves are almost always adequate for pushing material into the stomach and clearing the esophagus. If food or foreign bodies become lodged in the esophagus, secondary waves of peristalsis may lead eventually to muscle spasms that constrict tightly around the lodged material. These spasms frequently interfere with therapeutic attempts to remove obstructing objects in the esophagus.

When deglutition is not taking place, the body of the esophagus is relaxed, but the upper and lower sphincters remain constantly constricted. The constriction of these sphincters is important because of the differences in external pressure applied to the esophagus at different points along its length. During the inspiratory phase of breathing, the portion of the esophagus within the thorax is subjected to less-than-atmospheric pressure. If the two esophageal sphincters were not tightly closed, inspiration would cause aspiration of air from the pharynx and reflux of ingesta from the stomach into the body of the esophagus, in the same manner as inspiration draws air into the lung. Stomach contents would be drawn into the esophagus because inspiratory pressures in the thorax are lower than intraabdominal pressure. It is particularly important that the lower esophageal sphincter remain closed during inspiration because the mucosa of the esophagus is not equipped to resist the caustic actions of gastric contents; thus movement of stomach contents into the esophagus would cause damage to the esophageal mucosa.

In many species the action of the lower esophageal sphincter is aided by the anatomical nature of the attachment of the esophagus and stomach. The esophagus enters the stomach obliquely, allowing distention of the stomach to block the esophageal opening in a valve-like manner. During deglutition the longitudinal muscle of the esophagus contracts, shortening the esophagus and opening the valve at the junction with the stomach. This anatomical arrangement, along with the lower esophageal sphincter, is particularly well developed in the horse, making reflux of stomach material into the esophagus extremely rare in this species. In many cases, when the intragastric pressure of the horse is pathologically raised, the stomach ruptures before vomiting or esophageal reflux takes place.

The Function of the Stomach Is to Process Food into a Fluid Consistency and Release It into the Intestine at a Controlled Rate

Among animals there is tremendous diversity in the anatomy and motility patterns of the stomach. The following discussion applies best to the animals with the simplest stomachs, such as the dog and cat, but is probably also a reasonable description of the activity of the somewhat more complex stomachs of the pig, horse, and rat. The complex motility patterns of the ruminant stomach are discussed in Chapter 31.

The function of the stomach is to serve food to the small intestine. There are two important aspects of this function: rate of delivery and consistency of material. The stomach serves both as a storage vat to control the rate of delivery of food to the small intestine and as a grinder and sieve that reduces the size of food particles and releases them only when they are broken down to a consistency compatible with small-intestinal digestion.

The stomach is divided into two physiological regions, each of which has a different impact on gastric function. The proximal region, at the esophageal end of the stomach, serves a storage function, retaining food as it awaits eventual entry into the small intestine. The distal region serves a grinding and sieving function, breaking solid pieces of food down into particles small enough for small-intestinal digestion.

The Proximal Stomach Stores Food Awaiting Further Gastric Processing in the Distal Stomach

The major muscular activity in the proximal region of the stomach is of a weak, continuous-contraction nature. These tonic contractions tend to shape the gastric wall to its contents and provide gentle propulsion of material into the distal stomach. The major muscular reflex of the proximal stomach is adaptive relaxation (Figure 28-6). This reflex is characterized by relaxation of the muscles as food enters the stomach. Because of this relaxation, the stomach can dilate to accept large quantities of food without an increase in intraluminal pressure. Thus the proximal stomach serves as a food storage area. Because of the rather passive muscular activity of the proximal stomach, little mixing occurs there. In fact, food boluses tend to become layered in the stomach in the order in which they were swallowed. As the stomach empties, tension on the wall of the proximal stomach increases slightly, pushing food distally in the stomach, where it can be processed for transport into the duodenum.