V Gastrointestinal Tract
Anatomy and Physiology of the Gastrointestinal Tract
The gastrointestinal tract (GIT) is divided into distinct subunits, with morphological and functional differences: mouth including teeth, esophagus, stomach, pancreas and biliary tract, liver, duodenum, jejunum, ileum, colon, and anus. The different functions are reflected in macroscopic and microscopic anatomy. Macroscopically the stomach, for instance, has longitudinal, oblique, and circular muscle layers to mix and churn food and so aid digestion. Microscopically, the cells lining the stomach include specialized H cells that produce hydrochloric acid (see below).
In contrast, the ileum is an approximately 3 m long tube-like structure, with circular and smooth muscle optimized for peristalsis, and microscopically, the predominant cell type is the enterocyte, specialized for absorption of nutrients. The surface area of the ileum is increased by internal folds covered with projecting villi. These in turn are microscopically covered with microvilli, which project from the luminal surface of the epithelial cells.
The colon is specialized for extracting water, solidifying waste into feces before excretion. Bacteria in the colon aid metabolism by producing short chain fatty acids (SCFAs) such as butyrate, which is a source of energy for colonic epithelial cells. In this chapter we review important functions of the gastrointestinal tract, particularly the stomach, ileum, and colon, emphasizing nutritional and metabolic implications.
Gastrointestinal Tract-Specific Metabolic/Molecular Pathways and Processes
The stomach expands to accommodate food after a meal, initiates the release of hormones that coordinate subsequent events, and secretes hydrochloric acid (HCl), which converts pepsinogen into functional pepsin. Pepsin digests dietary proteins and peptides into smaller peptides that are further digested and absorbed as oligoand dipeptides in the duodenum, jejunum, and ileum.
HCl creates an environment that is inhospitable to most microorganisms. Epithelial cells are protected from the effects of HCl by a number of mechanisms including gastric mucus. Additionally, gastric acid favors the reduction of iron from ferrous to ferric (Fe2+ to Fe3+), which promotes its absorption in the proximal duodenum. In addition, intrinsic factor (IF) secreted by
Fig. 1 Overview of the gut with summary of main functions demonstrating absorption of water and electrolytes, carbohydrate, lipid, proteins, vitamins, and minerals. Gut
physiology is determined by the specialized cells lining the epithelium with absorption of different molecules in different parts of the gut the gastric mucosa binds to dietary cobalamin, protecting it from digestion and enabling absorption in the terminal ileum (Fig. 1).
The Small Intestine: Duodenum, Jejunum, and Ileum
The small intestine is differentiated along its length, with distinct functions occurring in duodenum, jejunum, and ileum. Acidic chyme from stomach is released gradually into the duodenum, where it is mixed with alkaline bile and pancreatic secretions rich in HCO –. The duodenal mucosa is specialized for absorption.
The pancreas produces the bulk of digestive enzymes for carbohydrates, lipids, and proteins, and bile acids contribute to the formation of mixed micelles of lipid, aiding their digestion.
Intestinal epithelial cells contribute to digestion by secreting enzymes such as lactase (see chapter “Lactose intolerance”) that are bound to their surface and express in their cell membranes protein transporters that enable nutrients to pass from the lumen of the intestine into the epithelial cell and then out of the cell and into the lymphatic and vascular circulation (lipophilic and hydrophilic substances, respectively). In addition, epithelial cells absorb electrolytes and metallic trace elements such as Na+, K+, Ca2+, Mg2+, Zn2+, Cu2+, and water. Paracellular movement of water and electrolytes also occurs, and the direction, either into or out of the lumen, depends on osmotic and ionic gradients. Tight junctions between epithelial cells are more effective distally, and paracellular transport in the healthy intestine plays only a minor role.
Digestion and absorption continue in the jejunum, where much of the electrolyte-rich fluid that is secreted by the stomach, pancreas, and duodenum is reabsorbed. Without this reabsorption, total body water, Na+, K+, and Mg2+ are rapidly depleted, presenting a clinical problem for patients who undergo intestinal resection leaving them with a jejunostomy or proximal ileostomy.
The terminal ileum is particularly important for the absorption of bile acids and Vitamin B12. As a consequence, disease of the ileum can cause vitamin B12 deficiency and diarrhea caused by loss of the enterohepatic circulation of bile salts (see chapter “Overview” under part “Liver”), with consequent excess of these in the colon, where they cause secretion of water and electrolytes . The ileum also acts as a barrier between the large and small intestine, with effects on bacterial populations, and intestinal motility. Finally, the ileum plays a prominent role for the immune system (see below) .
Absorption of carbohydrates requires digestion of complex carbohydrates into monosaccharides, as polysaccharides and disaccharides cannot be absorbed. Lactose, a disaccharide of galactose and glucose, is the main sugar in bovine and human milk and is digested by lactase, which is produced by intestinal epithelial cells. Lack of lactase causes lactose intolerance, in which colonic bacteria digest lactose to produce fermentation by-products, which, with the lactose, increases the osmotic gradient and results in diarrhea (see chapter “Lactose intolerance”). Furthermore, excess lactose may alter colonic bacteria. Avoiding dietary dairy can lead to Ca+ deficiency and potentially osteomalacia (Fig. 2).
The Large Intestine: Cecum, Colon, and Rectum
The main function of the specialized colonic epithelium is to reabsorb H2O from the 3–6 l/day of fluid that enters the cecum, so that approximately 200 ml is excreted as fecal waste. Reabsorbed water is accompanied by electrolytes, particularly Na+, K+, and Mg2+. Colonic bacteria metabolize fats and contribute to the provision of essential fatty acids. Tight junctions between colonic epithelial cells prevent salt and water loss from the interstitial tissue space and limit the translocation of bacteria and toxins from the colonic lumen into the circulation.
The practical importance of reabsorption is illustrated by patients who have undergone extensive resection of the small intestine. When they have a proximal jejunostomy or ileostomy, loss of salt and water means that they require regular intravenous supplementation, even when absorption of dietary carbohydrate, fat, and protein is sufficient. In such cases, anastomosis of the small intestine to the colon typically reverses dependence on intravenous fluids.
Colonic bacteria contribute metabolically to the host. Food residue in the colon is fermented, yielding gases such as methane (CH4), H2, and CO2 and short chain fatty acids (SCFAs), such as acetate, butyrate, and propionate. However, fermentation can also produce toxic metabolites (see below). Butyrate is a major energy source for colonic epithelial cells and its absence can result in inflammation (see also chapter “Colorectal cancer”).
Moreover, the mix of colonic bacterial species, termed the microbiome, varies between individuals. This variation may be associated with diseases including obesity and autoimmunity .