NROSCI/BIOSC 1070 and MSNBIO 2070 November 15, 2017 Gastrointestinal 1 Functions of the Digestive Tract
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NROSCI/BIOSC 1070 and MSNBIO 2070 November 15, 2017 Gastrointestinal 1 Functions of the Digestive Tract. The digestive system has two primary roles: digestion, or the chemical and mechanical breakdown of foods into small molecules that can absorbed, or moved across the intestinal mucosa into the bloodstream. In order to accomplish these functions, the secretion of enzymes, hormones, mucus, and paracrines by the gastrointestinal organs is needed. Furthermore, motility, or controlled movement of materials through the digestive tract is required. In addition to these primary functions, the gastrointestinal tract faces a number of challenges. Almost 7 liters of fluid must be released into the lumen of the digestive tract per day to allow for digestion and absorption to occur. Clearly, most of this fluid must be reabsorbed or dehydration will occur. Furthermore, the inner surface of the digestive tract is technically in contact with the external environment; for this reason, protective mechanisms are needed. In part, these mechanisms must protect against the secretions of the GI tract, including acid and enzymes. Anatomy of the Gastrointestinal System November 15, 2017 Page 1 GI 1 The anatomy of the GI system is illustrated in the previous 2 figures. The organs involved in digestion and absorption include the salivary glands, esophagus, stomach, small intestine, liver, pancreas, and large intestine. In addition, 7 sphincters control the movement of material and secretions between the organs. The total length of the GI tract is about 15 feet, of which 13 feet are comprised of intestine. The processed material within the GI tract is referred to as chyme. The wall of both the intestines and stomach is similar, in that it contains four (or five) layers: mucosa, submucosa, muscle layer (sometimes divided into 2 layers), and serosa. The mucosa is composed of epithelial cells, the lamina propria (connective tissue containing nerves and muscles), and muscularis mucosa (specialized smooth muscle). The mucosa has a number of specializations to increase surface area. Within the stomach, these occur as folds called rugae. Within the small intestine, a number of fingerlike projections, or villi, are present. The individual cells on the villi have further specializations that increase surface area; these specializations are called microvilli. In addition, invaginations (called gastric glands in the stomach and crypts in the intestine) exist in the GI tract. These invaginations are lined with secretory cells. Within the stomach, most of the epithelial cells of the mucosa are secretory. Six types of secretory cells exist in the stomach: Mucus-secreting cells Parietal cells (secrete hydrochloric acid) Chief cells (secrete pepsin) G cells (secrete the hormone gastrin) Enterochromaffin cells (secrete histamine) D Cells (secrete somatostatin) November 15, 2017 Page 2 GI 1 The submucosal layer contains large blood vessels and lymph vessels, and the submucosal plexus, a major component of the enteric nervous system. We will discuss the enteric nervous system in detail later in this lecture. The muscle layer of the gut is composed of two layers of smooth muscle: an inner circular layer and an outer longitudinal layer. Contraction of the circular layer decreases the diameter of the lumen, and contraction of the longitudinal layer shortens the tube. Between the two layers of muscle is the myenteric plexus, another component of the enteric nervous system. The outer serosa forms the wall of the GI tract. It is an extension of the peritoneal membrane that lines the abdominal cavity. Sheets of mesentery connect with the serosa to hold the intestines in place. Gastrointestinal Smooth Muscle The cells in each bundle of smooth muscle are linked by gap junctions; therefore, electrical signals travel easily from cell to cell. Thus, a layer of gastrointestinal smooth muscle forms a syncytium, in that an action potential elicited anywhere in a bundle will evoke a contraction of all surrounding muscle cells. Three types of electrical activity are important in control of contraction of gastrointestinal smooth muscle: slow waves, spikes, and resting membrane potential. Most gastrointestinal contractions occur rhythmically, and the slow waves play a key role in controlling these contractions. Slow waves are slow oscillations that occur at different frequencies at different points in the gut (3/minute in the body of the stomach to 12/ minute in the duodenum). These slow waves are presumably due to cycling changes in activity in the Na+—K+ pump. The slow waves mainly reflect the entry of sodium into the smooth muscle cell, and thus in general do not cause muscle contraction (recall that calcium that triggers smooth muscle contraction enters from the outside). Spike potentials occur when voltage-gated channels that pass calcium and sodium open. The opening of these channels allows calcium to enter the smooth muscle cell, which induces contraction. These channels have slow kinetics, which results in very long-lasting spikes. Thus, if the resting membrane potential is sufficiently depolarized, the spike potentials will occur at the crest of the slow waves. November 15, 2017 Page 3 GI 1 In other words, control of resting membrane potential is all important in determining whether gastrointestinal smooth muscle cells will contract. Depolarization of GI smooth muscle cells can be induced by: 1) Muscle stretch 2) Acetylcholine (released by cells of enteric nervous system) 3) Some specific gastrointestinal hormones Hyperpolarization of GI smooth muscle cells can be induced by: Norepinephrine and epinephrine (e.g., the effects of the sympathetic nervous system) Control of Activity of Gastrointestinal Smooth Muscle As noted above, two “plexuses” of nerve cells comprise the enteric nervous system of the gut. The first plexus is in the submucosal layer, and the second plexus is between the longitudinal and circular smooth muscle (myenteric plexus). These nerve cells receive innervation by the sympathetic and parasympathetic nervous system, but can function without this input. It was recognized over 100 years ago that a “coordinating network” of neurons must exist within the gut. This conclusion was based on the observation that isolated segments of gut (taken out of the body) could execute coordinated peristalsis. In the 1920s, the British physiologist Langley speculated that the nerve network in the GI system was a third component of the autonomic nervous system, and functioned much like the “neural net” of a primitive organism. However, the enteric nervous system was largely ignored until the 1970s, and most undergraduate texts don’t even mention it (they incorrectly state that the parasympathetic and sympathetic systems directly affect GI control). Today, we are beginning to understand that the functions of the enteric nervous system are indeed very complex. Here is the evidence to suggest that the enteric nervous system is indeed a “little brain:” • The neurons of the enteric nervous system release more than 20 neurotransmitters and neuromodulators, many of which are identical to molecules found in the brain. These neurotransmitters are sometimes called “non-adrenergic, non-cholinergic” to distinguish them from the “traditional” autonomic neurotransmitters: norepinephrine and acetylcholine. The transmitters of the enteric nervous system will be discussed below, but they include serotonin, Vasoactive Intestinal Peptide (VIP), and Nitric Oxide. • The support cells of neurons in the enteric nervous system are more similar to the astroglia of the brain than to the Schwann cells of the peripheral nervous system November 15, 2017 Page 4 GI 1 • The capillaries that surround ganglia within the enteric nervous system are not very permeable and create a diffusion barrier that is similar to the blood-brain barrier of cerebral blood vessels • Reflexes resulting from stimulation of sensory receptors in GI tract can be integrated and elicited entirely within the enteric nervous system. Thus, the enteric nervous system must have the “sophistication” of coordinating these responses. Organization of the Enteric Nervous System In general, the enteric nervous system is organized into two sheets, the submucosal plexus and the myenteric plexus. The submucosal plexus mainly regulates secretory functions and vasomotor control, whereas the myenteric plexus mainly regulates motility. In reality, the cell bodies in the submucosal and myenteric plexus are concentrated into ganglia, with interganglionic fiber tracts interconnecting them. November 15, 2017 Page 5 GI 1 Why does the Enteric Nervous System Exist? In large part, the enteric nervous system serves as a “pattern generator” for the carefully coordinated sequence of contractions that results in motility. By relinquishing this control to the periphery, the central autonomic systems do not have to worry about coordinating this activity. In large part, the pacemaker system in the heart serves a similar role. Pattern generators in the central nervous system like the respiratory pattern generator and the locomotion generator follow the same idea of “higher centers” relinquishing control of stereotyped functions to lower- level coordinators. One clear response that the enteric nervous system produces is the “migrating action potential complex” (or “migrating motor complex”) which propagates through both normal gut and that removed from the body and placed in a tissue bath. Many hours after eating a meal, when the digestive system is not influenced