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Humans are in constant contact with a variety of xenobiotics. In addition to its critical role in absorbing nutrients, the gastrointestinal (GI) tract forms the initial functional barrier between ingested material and the body. An understanding of the GI tract’s structure, physiology, and innervation is critical to the toxicologic concepts of absorption, motility, and toxic insult. This chapter discusses the normal role of the GI tract and its relationship to toxicology. Anatomic, pathologic, and microbiologic principles are discussed, including the role of the GI tract in the metabolism of xenobiotics. Examples of GI pathologies and their clinical manifestations are discussed, with examples when appropriate.


The luminal GI tract can be divided into five distinct structures: oral cavity and hypopharynx, esophagus, stomach, small intestine, and colon (Fig. 20–1). These environments differ in luminal pH, specific epithelial cell receptors, and endogenous flora. The transitional areas between these distinct organs have specialized epithelia and muscular sphincters with specific functions and vulnerabilities. Knowledge of the anatomy of these transition zones is particularly important for the localization and management of foreign bodies. The functions of the pancreas and liver are closely integrated with those of the luminal organs. The pancreas is discussed here; the liver and its metabolic functions are discussed in Chaps. 13 and 23.

FIGURE 20–1.

Anatomy of the gastrointestinal system. (Modified with permission from Mescher AL: Junqueira’s Basic Histology. 13th ed. New York: McGraw-Hill; 2013.)

The visceral structures of the GI tract are composed of several layers, including the epithelium, lamina propria, submucosa, muscle layers, and serosa (the last of which is only present in intraperitoneal organs). As the transition is made throughout the GI tract, differences in luminal pH, epithelial cell receptors, muscularity, and endogenous flora are encountered, affecting the absorption and metabolism of individual xenobiotics.

The epithelium, the innermost layer of the GI tract, is the most specialized cell type in the intestine and is composed of epithelial, endocrine, and receptor cells. Epithelial cells have polarity, with the basal surface facing the lamina propria and the apical surface facing the lumen. They are further specialized for specific functions of secretion or absorption. Additionally, the epithelial cells form part of the mucosal immune defense, where they are able to detect the presence of microbial pathogens and downregulate the immune system in the presence of nonpathogenic or probiotic microbes. The major barrier to penetration of xenobiotics and microbes is the GI epithelium, a single-cell-thick membrane. The cell membrane is a semipermeable lipid bilayer that contains aqueous pores through which certain materials can pass, depending on their on size or molecular structure. The membrane is not continuous because it consists of individual epithelial cells; however, these cells are joined to each other by structures known as tight ...

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