The absorption of nutrients from the intestine relies on its blood supply, which is different from other organ systems. Instead of directly returning to the heart, venous drainage from the gastrointestinal (GI) tract enters the portal circulation, which leads to the liver. This means that the liver receives a significant portion of its blood supply from sources other than the arterial circulation. Additionally, blood flow in the GI tract is dynamically regulated. Approximately 25% of cardiac output is directed towards splanchnic blood flow, which is disproportionate to the mass of the GI tract it supplies. After a meal, blood can be redirected from muscle to the GI tract in order to meet the metabolic needs of the gut wall and remove absorbed nutrients.

The lymphatic drainage of the GI tract is responsible for transporting lipid-soluble substances that are absorbed across the intestinal wall. Lipids, along with other lipid-soluble molecules like certain vitamins and drugs, are packaged into large particles that cannot pass into capillaries. Instead, they enter lymph vessels within the intestinal wall. These lymph vessels eventually drain into larger lymph ducts, which then connect to the thoracic duct and enter the systemic circulation on the arterial side. This has significant implications for lipid metabolism and the delivery of drugs directly into the systemic circulation.

The wall of the tubular gut consists of various layers composed of specialized cells. The innermost layer, called the mucosa, includes the epithelium, the lamina propria, and the muscularis mucosae. The epithelium is a single layer of specialized cells that line the lumen of the GI tract, extending along the tube and to the glands and organs that drain into it. Within this layer, several types of specialized epithelial cells can be found. The most abundant are absorptive enterocytes, which express numerous proteins crucial for the digestion and absorption of macronutrients. Enteroendocrine cells contain secretory granules that release regulatory peptides and amines to help regulate GI function. Gastric mucosa cells are specialized for proton production, while mucin-producing cells throughout the GI tract generate a glycoprotein called mucin, which safeguards the GI tract and lubricates its contents.

The columnar epithelial cells are connected by tight junctions, which are complexes of proteins located within the cells and on their membranes. The tightness of these junctions is regulated throughout the postprandial period. The nature of the epithelium varies depending on the specific region of the digestive tract, aligning with its predominant function. For example, the intestinal epithelium is designed for absorption and facilitates the selective uptake of nutrients, ions, and water. Conversely, the esophagus has a squamous epithelium without an absorptive role. It primarily serves as a conduit for transporting swallowed food and therefore requires protection, provided by the squamous epithelium, from rough food such as fiber.

The surface area of the epithelium is increased by the presence of villi and crypts. Villi are finger-like projections that extend from the mucosa, enhancing its surface area. Crypts, on the other hand, are folds or invaginations in the epithelium. The epithelium that lines the GI tract undergoes continuous renewal and replacement through the division of cells. In humans, this process takes approximately three days. The proliferating cells are primarily located in the crypts, where there is a proliferative zone containing intestinal stem cells.
The blood supply to the intestine is important for carrying absorbed nutrients to the rest of the body. Unlike other organ systems of the body, venous drainage from the GI tract does not return directly to the heart but first enters • Fig. 27.1 General anatomy of the GI system and its division into functional segments.
the portal circulation leading to the liver. Thus the liver is unusual in receiving a considerable part of its blood supply from other than the arterial circulation. GI blood flow is also notable for its dynamic regulation. Splanchnic blood flow receives about 25% of cardiac output, an amount disproportionate to the mass of the GI tract it supplies. After a meal, blood can also be diverted from muscle to the GI tract to subserve the metabolic needs of the gut wall and also to remove absorbed nutrients.
The lymphatic drainage of the GI tract is important for the transport of lipid-soluble substances that are absorbed across the GI tract wall. As we will see later, lipids and other lipid-soluble molecules (including some vitamins and drugs) are packaged into particles that are too large to pass into the capillaries and instead pass into lymph vessels in the intestinal wall. These lymph vessels drain into larger lymph ducts, which finally drain into the thoracic duct and thus into the systemic circulation on the arterial side. This has major physiological implications in lipid metabolism and also in the ability of drugs to be delivered straight into the systemic circulation.
The wall of the tubular gut is made up of layers consisting of specialized cells (
Fig. 27.2
The mucosa is the innermost layer of the GI tract. It consists of the epithelium, the lamina propria, and the muscularis mucosae. The epithelium is a single layer of specialized cells that line the lumen of the GI tract. It forms a continuous layer along the tube and with the glands and organs that drain into the lumen of the tube. Within this cell layer are • Fig. 27.2 General organization of the layers composing the wall of the GI tract.
a number of specialized epithelial cells; the most abundant are cells termed absorptive enterocytes, which express many proteins important for digestion and absorption of macronutrients. Enteroendocrine cells contain secretory granules that release regulatory peptides and amines to help regulate GI function. In addition, cells in the gastric mucosa are specialized for production of protons, and mucin-producing cells throughout the GI tract produce a glycoprotein (mucin) that helps protect the GI tract and lubricate the luminal contents.
The columnar epithelial cells are linked together by intercellular connections called tight junctions. These junctions are complexes of intracellular and transmembrane proteins, and the tightness of these junctions is regulated throughout the postprandial period. The nature of the epithelium varies greatly from one part of the digestive tract to another, depending on the predominant function of that region. For example, the intestinal epithelium is designed for absorption; these cells mediate selective uptake of nutrients, ions, and water. In contrast, the esophagus has a squamous epithelium that has no absorptive role. It is a conduit for transportation of swallowed food and thus needs some protection, provided by the squamous epithelium, from rough food such as fiber.
The surface area of the epithelium is arranged into villi and crypts (Fig. 27.3 ). Villi are finger-like projections that serve to increase the surface area of the mucosa. Crypts are invaginations or folds in the epithelium. The epithelium lining the GI tract is continuously renewed and replaced by dividing cells; in humans this process takes about 3 days. These proliferating cells are localized to the crypts, where there is a proliferative zone of intestinal stem cells.