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The GI tract, pancreas, and liver are responsible for digestion; absorption of fluids, electrolytes, and nutrients; removal of waste products; and metabolism of medications and other exogenous materials. The epithelial lining of the GI tract is larger than a tennis court. These epithelial cells have a rapid turnover, with a lifespan of 3 to 7 days, and have considerable interaction with endogenous and exogenous materials. The enteric nervous system ( Chapter 138 ), which is composed of a complex array of neurons and ganglia organized around the myenteric (Auerbach) and submucosal (Meissner) plexus located within the wall of the esophagus, stomach, and intestinal tract, contains between 10 and 100 million neurons—equal to the total number in the spinal cord. Although it is an independent nervous system, complex interactions with the autonomic and central nervous systems are necessary for normal function. Recent evidence suggests abnormal interactions among the enteric, autonomic, and central nervous systems in the development and continuation of symptoms in functional bowel disorders such as irritable bowel syndrome ( Chapter 139 ). The immunologic system of the GI tract is the largest immune organ in the body ( Chapter 42 ). It consists of luminal and epithelial barrier defenses, cellular components such as T and B cells, and noncellular inflammatory mediators. It has the overwhelmingly complex task of coexisting with luminal antigens (food), host proteins, and commensal bacteria while simultaneously differentiating these “good” antigens from “bad” antigens such as pathogenic bacterial proteins and transformed epithelial cells. The GI immune system plays a role in systemic autoimmune disorders and immune tolerance. The GI endocrine system is stimulated by the ingestion of food. Secretion of hormones from endocrine cells responds to nutrients and to stimulation from the central nervous system. The motility of the GI tract depends on a complex interaction between smooth muscle and the enteric nervous system. The interstitial cells of Cajal act as pacemakers of the GI tract and are responsible for the smooth, orderly transport of material from the mouth to the anus ( Chapter 138 ). With aging, the GI tract undergoes numerous changes. Epithelial cells interact with the environment and, given the appropriate genetic background, may undergo neoplastic transformation. Colon cancer ( Chapter 203 ) is the second most common malignancy in the United States, and the GI tract collectively has more cancers than any other organ in the body.