19.1 Structure
The gastrointestinal (GI) system, or alimentary canal, consists of the mouth, pharynx, esophagus, stomach, small intestine, cecum, colon, rectum, and associated secretory organs and glands (salivary glands, exocrine pancreas, gallbladder, and liver). Figure 19.1 shows the GI organs and their individual general functions. However, their overall function is to obtain nutrients and water from the external environment.
Fig. 19.1 
Functions of gastrointestinal (GI) organs.
The GI system extends from the mouth to the rectum and includes secretory organs and glands. The function of each structure and the transit time of the food bolus or chyme from food intake are shown.
Embryology of the gastrointestinal tract
The GI tract and its associated organs (liver, gallbladder, and pancreas) develop from endoderm. The peritoneum, which covers the GI tract, develops from mesoderm. Note that the pancreas, duodenum (descending, horizontal, and some of the ascending part), ascending and descending colon, cecum (variable portions), and upper two-thirds of the rectum are secondarily retroperitoneal; that is, they were intraperitoneal when formed but became retroperitoneal during fetal development.
Layers of the Gastrointestinal Tract
Working from the lumen outward, the layers of tissue found in most of the GI tract are the mucosa, submucosa, muscularis propria, and serosa (Fig. 19.2).
Mucosa
Mucosa is composed of epithelium, lamina propria, and muscularis mucosae.
– Stratified squamous epithelium is found in the esophagus and rectum. Columnar epithelium is found in the rest of the GI tract.
The mucosa in the stomach forms prominent folds (rugae) that serve to increase its surface area. The mucosa in the small intestine has villi and microvilli that serve to increase its surface area.
– The lamina propria is a layer of connective tissue.
– The muscularis mucosae is a layer of smooth muscle. Contraction of the muscularis mucosae alters the surface area for absorption or secretion.
Submucosa
The submucosa is a layer of loose connective tissue with collagen and elastin fibers.
Muscularis Propria (Externis)
The muscularis propria (externis) is a muscular layer composed of circular muscle and longitudinal muscle.
– These muscles are responsible for peristalsis.
Serosa (Adventitia)
The serosa is a fibrous layer that is continuous with the peritoneal lining.
Fig. 19.2 Wall structure and enteric nervous system of the GI tract.
The enteric plexus is the portion of the autonomic nervous system that specifically serves all organs of the GI tract. The submucosal plexus is located between the submucosal layer and circular muscle. The myenteric plexus is located between the circular muscle and the longitudinal muscle. The enteric plexus is subject to modulation by the parasympathetic and sympathetic nervous systems.
From Thieme Atlas of Anatomy, Head and Neuroanatomy, © Thieme 2007, Illustration by Karl Wesker.
Immune Function of the Gastrointestinal Tract
The mass of immunocompetent lymphoid cells and tissue in the GI tract is equivalent to that found in the rest of the body. Immunocytes can be found in the mucosa and submucosa and within Peyer patches in the terminal ileum. These immunocytes include T and B lymphocytes, plasma cells, mast cells, macrophages, and eosinophils. When they encounter an antigen, they respond by secreting inflammatory mediators (e.g., histamine, prostaglandins, leukotrienes, and cytokines). These stimulate GI motility and the secretion of water and electrolytes, thus promoting expulsion of the offending antigen.
Table 19.1 summarizes the immune defenses of the GI tract.
Inflammatory bowel diseases
There are two types of inflammatory bowel disease (IBD): Crohn disease and ulcerative colitis. Crohn disease is a chronic inflammatory disease that can affect the entire GI tract, but most commonly affects the terminal ileum and colon. It causes ulcers, fistulas (abnormal communications), and granulomata, producing symptoms such as fever, diarrhea, weight loss, and abdominal pain. Ulcerative colitis is a recurrent inflammatory disease of the colon and rectum that produces bloody diarrhea, weight loss, fever, and abdominal pain. Acute attacks of Crohn disease and ulcerative colitis are treated with sulfasalazine and 5-aminosalicylate (5-ASA) drugs. Crohn disease also may involve treatment with steroids. These drugs inhibit tissue necrosis factor α (TNFα) and interleukins thus reducing the inflammatory response.
Irritable bowel syndrome
IBS is a chronic idiopathic condition. Symptoms include abdominal pain, bloating, and cramps that are associated with bowel habit alteration in the form of constipation or diarrhea. Treatment is guided by the symptoms and their severity. Mild IBS may respond to dietary changes. Drugs may be called for in patients with moderate to severe symptoms. Antispasmodics (e.g., hyoscyamine and dicyclomine), laxatives (docusate, bisacodyl, senna, or osmotic agents), and loperamide are standard. In severe cases with diarrhea, alosetron, a potent and selective antagonist of the 5-HT3 receptor that decreases intestinal motility and pain, may be used with caution, as it can lead to severe constipation. (Note: IBS is not associated with pathophysiological changes in gut structure and is diagnosed only when all else has been excluded.)
Celiac disease
Celiac disease is a GI disorder caused by the consumption of gluten-containing foods (e.g., bread and pasta). Gluten triggers an immune reaction in the small intestine that causes villous atrophy and GI malabsorption. Symptoms usually include diarrhea, abdominal pain, and bloating; however, it can present with signs of the malabsorption aspect, for example, anemia (from iron, vitamin B12, or folate deficiency), bleeding (from vitamin K deficiency), osteomalacia (from vitamin D deficiency), edema (from protein deficiency), and failure to thrive. Patients are likely to give a positive hydrogen breath test due to destruction of the microvilli and concomitant loss of lactase. There is no treatment for this condition, but it can be managed by permanently avoiding all foods containing gluten.
19.2 Regulation of the Gastrointestinal Tract
Neural Control
The GI system is richly innervated by both extrinsic and intrinsic nerves. Extrinsic nerves are those that comprise the autonomic nervous system (ANS). Intrinsic nerves are those that comprise the enteric nervous system, a subdivision of the peripheral nervous system. The enteric nervous system relays information from the ANS and is also able to directly and independently regulate many GI functions.
Extrinsic Innervation (Autonomic Nervous System)
Extrinsic nerves provide for long reflexes, which coordinate activities at widely separated sites along the GI tract.
Parasympathetic division of the autonomic nervous system. In general, the parasym-pathetic division stimulates GI functions.
– The parasympathetic neural supply for the gut comes from the vagus and pelvic nerves.
– The vagus nerve innervates the esophagus, stomach, pancreas, and proximal colon. Vagovagal reflexes are long reflexes in which both the afferent and efferent components are mediated by the vagus nerve.
– The pelvic nerves innervate the distal colon, rectum, and anus.
– Preganglionic parasympathetic fibers synapse with nerves of the intrinsic (enteric) nervous system (the submucosal and myenteric plexus).
– Fibers then project from cell bodies in the ganglia of these plexuses to secretory cells, endocrine cells, and smooth muscle cells in the GI system.
Sympathetic division of the autonomic nervous system. In general, the sympathetic division inhibits GI functions.
– Sympathetic preganglionic cholinergic nerves synapse in the prevertebral ganglia.
– Sympathetic postganglionic nerves innervate the GI tract from the celiac, superior mesenteric, and superior and inferior hypogastric plexus.
– Postganglionic sympathetic fibers synapse in the submucosal and myenteric plexus of the intrinsic nervous system.
– Some postganglionic fibers synapse directly with blood vessels and smooth muscle.
– Fibers then project from cell bodies in the ganglia of these plexus to secretory cells, endocrine cells, and smooth muscle in the GI tract.
Intrinsic Innervation (Enteric Nervous System)
The enteric nervous system possesses all the elements necessary for short reflex regulation of GI functions, that is, modification of motility and secretory activity by afferent and efferent nerves entirely within the GI tract. It is able to do this without modulation from the extrinsic nervous system, with the exception of the proximal esophagus and external anal sphincter.
Submucosal plexus (Meissner plexus)
– This is located in the submucosal layer between the mucosa and circular muscle in the wall of the GI tract.
– It principally controls GI secretions and blood flow.
Myenteric plexus (Auerbach plexus)
– This is located between the longitudinal and circular layers of smooth muscle in the wall of the GI tract.
– It principally controls the motility of GI smooth muscle.
Hormonal Control
GI hormones are released from endocrine cells in the mucosa of certain regions of the GI system, particularly the antrum of the stomach and the upper small intestine.
The major hormones secreted by the GI system are gastrin, secretin, glucagon-like peptide 1 (GLP-1), cholecystokinin, and glucose-dependent insulinotropic peptide (GIP). The control of their release and their actions are summarized in Table 19.2.
Paracrine Control
Paracrine substances are signaling molecules released by cells in the GI mucosa that diffuse through interstitial fluid to nearby target cells, where they exert their effects.
The two key paracrine substances of the GI system are histamine and somatostatin. The control of their release and their actions are summarized in Table 19.3.
Neurocrine Control
Neurocrine substances are peptides synthesized by neurons of the GI tract. They are released from an axon following an action potential and diffuse across the synaptic cleft to their target tissue.
The three neurocrine substances in the GI tract are vasoactive intestinal peptide, gastrin-releasing peptide (bombesin), and enkephalins. The control of their release and their actions are summarized in Table 19.4.
