Villus

FIGURE 24.4 In the small intestine, fatty acids combine with bile salts in mixed micelles, which deliver fatty acids to epithelial cells that cover the intestinal villi. Triacylglycerols are formed within the epithelial cells. 

Drugs taken orally are slow to act. Most are absorbed in the small intestine where the villi, which penetrate into the lumen, present a large surface area. Unfortunately in order to pass through the gut wall into the bloodstream the drug has to become dissolved in its cell s membranes and to achieve this it needs to be lipid-soluble. 

To date, there is very little known about if and how phytochemicals modulate the metabolism of GIT tissues other than the liver. Of particular interest are the xenobiotic metabolizing enzymes of the GIT, which are involved with transformation of drugs and toxins. Whereas the metabolic activities of the resident microflora dominate in the large intestine, mucosal enzyme activities are more important in the small intestine where bacterial densities are lower and the villi and microvilli increase the area of exposure. 

Fig. 4 Diagrammatic sketch of the small intestine illustrating the projection of the villi into the lumen (left) and the anatomic features of a single villus (right). (Modified from Ref. 7.)...

The third mucosal layer is that lining the entire length of the small intestine and which represents a continuous sheet of epithelial cells. These epithelial cells (or enterocytes) are columnar in shape, and the luminal cell membrane, upon which the microvilli reside, is called the apical cell membrane. Opposite this membrane is the basal (or basolateral) plasma membrane, which is separated from the lamina propria by a basement membrane. A sketch of this cell is shown in Fig. 5. The primary function of the villi is absorption. 

Structurally, the large intestine is similar to the small intestine, although the luminal surface epithelium of the former lacks villi. The muscularis mucosa, as in the small intestine, consists of inner circular and outer longitudinal layers. Figure 6 illustrates a photomicrograph and diagrammatic sketches of this region. 

Although most drugs are absorbed from the intestine by the blood capillary network in the villi, they can also be taken up by the lymphatic system (an integral and necessary part of the vascular system, the function of which is to collect extra tissue fluid and return it to the vascular compartment), particularly by M cells that reside in the Peyer s patch regions of the intestine. Peyer s patches have also been implicated in the regulation of the secretory immune response. Wachsmann et al. [277] reported that an antigenic material encapsulated within a liposome, when administered perorally, is taken up by these M cells and exhibited better saliva and serum IgA (primary and secondary)... 

Figure 2.4 Schematic of the villi fingers covered by a monolayer of epithelial cells, separating the lumen from the blood capillary network [63,69]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

The surface area in the luminal side of the small intestine per unit length of the serosal (blood) side is enormous in the proximal jejunum, and steadily decreases (to about 20% of the starting value [62]) in the distal portions of the small intestine. The surface area is increased threefold [69] by ridges oriented circumferentially around the lumen. Similar folds are found in all segments of the GIT, except the mouth and esophagus [66]. Further 4—10-fold expansion [62,69] of the surface is produced by the villi structures, shown schematically in Fig. 2.4. The layer of epithelial cells lining the villi structures separate the lumen from the circulatory system. Epithelial cells are made in the crypt folds of the villi, and take about... 

The tips of villi have the lowest pHm values, whereas the crypt regions have pHm > 8 values [70]. Most remarkable was that an alkaline microclimate (pHm 8) was observed in the human stomach, whose bulk pHfo is generally about 1.7. In the stomach and duodenum, the near-neutral microclimate pH was attributed to the secretion of HCO3 from the epithelium [70]. 

H Daniel, B Neugebauer, A Kratz, G Rehner. Localization of acid microclimate along intestinal villi of rat jejunum. Am J Physiol 248 G293-G298, 1985. 

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 goblet cells produce mucus. The absorptive cells, found in a single layer covering the villi, are far more abundant. Taken together, the villi increase the absorptive surface area another 10-fold. 

Microvilli are microscopic projections found on the luminal surface of the absorptive cells. Each absorptive cell may have literally thousands of microvilli forming the brush border. These structures increase the surface area for absorption another 20-fold. Together, these three anatomical adaptations of the intestinal mucosa — plicae circulares, villi, and microvilli — increase the surface area as much as 600-fold, which has a profound positive effect on the absorptive process. 

Symons, L.E.A. (1965) Kinetics of epithelial cells and morphology of villi and crypts in the jejunum of the rat infected with Nippostrongylus brasiliensis. Gastroenterology49, 158-168. 

Fig. 18.2. Histological appearance of haematoxylin and eosin-stained jejunum of (A) uninfected control, with villi and crypts of normal lengths (B) day 13 p.i.

T cell activation in the lamina propria is associated with epithelial cell shedding, leading to loss of villi. It has been postulated that this is mediated by increased production of matrix metalloproteases (MMP), which, by degrading the lamina propria matrix, represent a major pathway by which T cells cause injury in the gut (Pender et al., 1997). Production of MMPs also facilitates movement of cells out of the vasculature into sites of inflammation and contributes substantially to the degradation of connective tissue during inflammatory disease (Stetler-Stevenson, 1996). Furthermore, MMPs are required for the release of soluble TNF-a from its membrane... 

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