In many ways, the gastrointestinal (GI) tract is a remarkable organ. The embryonic endoderm will give rise to the future GI tract. The GI tract will acquire multiple cell types that will be dispersed into two planes: a vertical plane that allows one to recognize different layers of the bowel wall and a horizontal plane that develops into the esophagus, stomach, small intestine, colon, and anus. Although these cell types will resemble one another, important histologic differences allow specific physiologic functions to be carried out in each anatomic region. Interactions between cell populations regulate subsequent patterns of gene expression and organ development (1).

The physiology of the GI tract is also impressive. It serves as the digestive organ of the body, taking in everything that is swallowed and turning it into useful nutrients or discarding what is left over as waste. These processes begin in the mouth and terminate at the anus. While digesting everything to which it is exposed and breaking it down into smaller, absorbable chemical substances, the gut is itself able to withstand these processes and avoid autodigestion. Complex neuromuscular interactions allow the GI tract to move food and liquids from one section of the gut to the next, while at the same time controlling the passage of food in such a way that maximum digestion and absorption occurs in each of the appropriate spots. Even in a single organ, such as the small intestine, a differentiation gradient exists such that different substances are preferentially absorbed at different intestinal sites and through different parts of the cell. Not everything taken into the mouth and swallowed is healthy for the patient. Therefore, the GI tract serves as a major interface between the outside world and the rest of the body. The gut is continuously exposed to toxins and infectious organisms, yet it is often capable of eliminating these agents without causing any harm to itself. Not surprisingly, breakdown in these defense processes often results in disease. This generally occurs when the integrity of the bowel wall becomes compromised. The gut also serves as a major immune organ. It is the major site of the generation of mucosal immunity, hence the utility of oral vaccines. These immunologic processes largely take place in the small bowel. Finally, the GI tract is a major endocrine organ.

In humans, the gut is divided into four major organs: esophagus, stomach, small intestine, and large intestine. These are separated by sphincters that control the passage of contents from one organ to the next. The junctions between organs are identifiable by an abrupt change in the mucosal nature and by the presence of the sphincters.

Multiple interactions occur during development between and within the three germ layers (endoderm, mesoderm, and ectoderm). Each of these layers may reciprocally induce development of other layers. The endoderm induces the mesoderm (2). It also confers a dorsal-ventral pattern on it (2). The endoderm and ectoderm contact one another in the 2- to 4-week embryo. The endoderm, which forms the roof of the yolk sac, gives rise to the future gut, creating the majority of the epithelial lining of the GI tract, biliary passages, liver, and pancreas. The primitive gut temporarily consists of foregut, midgut, and hindgut. The splanchnic mesoderm surrounding the primitive gut forms the muscular and connective tissue layers. Embryologic development takes place with a large number of inducers that share overlapping expression patterns and redundant functions. The core of this system consists of a set of structurally similar genes known as homeobox genes. The embryology of each region is discussed in detail in the relevant chapters.

Multipotential neural progenitors give rise to various derivatives, including neurons, glia, and ganglia, as the result of local environmental signals. These progenitors differentiate
based on specific molecules they encounter either during their migration or within the organ in which they terminally differentiate as discussed in detail in Chapter 10.

Abundant endocrine cells are present by 8 weeks’ gestation. The diversity of the GI endocrine cell component is established early. There is a higher density of endocrine cells in both the proximal duodenum and the distal colon and rectum compared with other areas. Endocrine cell numbers increase with age, roughly paralleling the growth of the gut. The full adult profile is attained by the second trimester. The endocrine system is discussed in detail in Chapter 17.

Peripheral lymph nodes develop by the second month of gestation. Mononuclear cell aggregates are also identified in the fetal intestine in proximity to the endodermal epithelium.

The GI tract undergoes continuous development and proliferation. Its mucosa varies from the esophagus to the colon, and it contains multiple cell types. New cells form from stem cells within the basal layers of the anal and esophageal squamous epithelium, in the mucous neck region of the stomach, or from the bases of the crypts in the small intestine and colon (Fig. 1.1). Cells then migrate out of the proliferative zone and differentiate into multiple cell lineages. The differentiation pattern of the gut epithelium is influenced by other cells in its environment (3). Eventually, the cells are shed into the lumen or undergo apoptosis. Cellular life span is 5 to 7 days in the duodenum and jejunum, 4 to 5 days in the ileum, and 4 to 6 days in the large intestine. Specific details of cell proliferation in the esophagus, stomach, small intestine, and colon are discussed in the relevant chapters.

The intestine alters its rates of cellular renewal and adapts to surgical, nutritional, and other toxic stimuli, as well as to physiologic stress and disease states. Stem cells show three general features: (a) the capacity to undergo asymmetric division, producing one daughter that remains a stem cell and another that undergoes a seemingly irreversible commitment to enter a differentiation pathway; (b) proliferative potential; and (c) the ability to retain a position in a particular environmental niche (4,5). Some stem cells are unipotential, giving rise to a single differentiated phenotype, whereas others are multipotential, giving rise to multiple cell types.

In general, the gut consists of four concentric layers as one progresses outward from the lumen: the mucosa, submucosa, muscularis propria, and serosa or adventitia (Fig. 1.2). These layers are easily visualized histologically and can also be imaged using ultrasound. The high correlation that exists between the ultrasound image and the histologic features allows one to use ultrasound to provide diagnostic information about the status of the GI tract.