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Humans are in constant contact with 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 structure, physiology, and innervation of the GI tract 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. Types of GI pathologies and their clinical manifestations are discussed, with examples when appropriate.


The luminal GI tract is divided into 5 distinct structures: oral cavity and hypopharynx, esophagus, stomach, small intestine, and colon (Fig. 18–1). These environments differ in luminal pH, epithelial cell receptor types, and endogenous flora. The transitional areas between these distinct organs have specialized epithelia and muscular sphincters with specific functions and vulnerabilities. Knowing 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. 11 and 21.

FIGURE 18–1.

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

The visceral structures of the GI tract are composed of several layers, including the epithelium, lamina propria, submucosa, muscularis 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. The basal surface of epithelial cells faces the lamina propria, and the apical surface faces 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 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 pass, depending on size and 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 junctions. The tight junctions have a gap of about 8 ...

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