Intestine, absorptive surface area

The plicae circulares, or circular folds, form internal rings around the circumference of the small intestine that are found along the length of the small intestine. They are formed from inward foldings of the mucosal and submucosal layers of the intestinal wall. The plicae circulares are particularly well developed in the duodenum and jejunum and increase the absorptive surface area of the mucosa about threefold. Each plica is covered with millions of smaller projections of mucosa referred to as villi. Two types of epithelial cells cover the villi ... 

The large intestine has a considerably smaller absorptive surface area than the small intestine, but it may still serve as a site of drug absorption, especially for compounds that have not been completely absorbed from the small intestine. However, little absorption occurs... 

The gastrointestinal tract is a major site site of absorption primarily because of its very large surface area and extensive blood flow (Table 11.2). Most of the absorptive surface area of the gastrointestinal tract is in the small intestine and thus most absorption from the gastrointestinal tract occurs there. 

The large internal surface area of the small intestine is attributable to its length, folding, and the presence of villi and microvilli within its lumen. The villi contain capillaries and protrude into the lumen of the small intestine. There are approximately four to five million villi in the small intestine. Each villus has many microvilli as its outer surface (Figure 11.3). The microvilli represent the absorptive barrier of the small intestine. The stomach and large intestine do not contain villi and, therefore, have a small absorptive surface area compared with the small intestine. 

The epithelium is supported underneath by lamina propria and a layer of smooth muscle called muscularis mucosa (3-10 cells thick). These three layers, i.e., the epithelium, lamina propria, and muscularis mucosa, together constitute the intestinal mucosa.On the apical surface, the epithelium along with lamina propria projects to form villi. The cell membranes of epithelial cells that comprise the villi contain uniform microvilli, which give the cells a fuzzy border, collectively called a brush border. These structures, although greatly increase the absorptive surface area of the small intestine, provide an additional enzymatic barrier since the intestinal digestive enzymes are contained in the brush border. In addition, on the top of the epithelial layer lies another layer, the UWL, as previously described. The metabolic and biochemical components of the epithelial barrier will be discussed. 

Several factors originating from the chemical structure and property of the drug molecule, and from the physiology within the environment in the GI tract, affect the flow of molecules across the intestinal membrane. These factors include solubility, partition coefficient, pffa, molecular weight, molecular volume, aggregate, particle size, pH in the lumen and at the surface of the membrane, GI secretions, absorptive surface area, blood flow, membrane permeability and enzymes (for more factors, see Ungell 1997, and Table 4.8). Complete absorption occurs when the drug has a maximum permeability coefficient and maximum solubility at the site of absorption (Pade and Stavchansky 1998). 

Fig. 2 Effects of mucosal structure on absorptive surface area of the small intestine.

The stomach is the next major portal of entry of substances taken orally and swallowed. The rapid transit through the mouth and esophagus leaves little time for absorption in those regions. The makeup of the pill or capsule and how it is taken also determine the site of absorption. If a tablet is taken with water on an empty stomach, it will likely pass rapidly through the stomach and into the small intestine. On the other hand, if taken with food, the substance will likely spend more time in the stomach. The surface of the stomach, called the gastric mucosa, is made up of a series of infoldings which greatly increases the absorptive surface area. The pH of the stomach is usually quite low (pH < 3 in humans) and therefore substances which are weak acids remain in undissociated form and are easily absorbed. Their rate of absorption will depend on the lipid solubility. 

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

It will then depend for its absorption on the large surface area of the intestine. 

Clark, D. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J. Pharm. Sci. 2000, 88, 807-814. 

Artursson, P., Bergstrom, A. S. Intestinal absorption the role of polar surface area. 

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