Intestinal mucosal surface

It is somewhat counterintuitive to think that the aqueous solubility of a Ca source has liffle impacf on ifs capacify fo be absorbed at the intestinal mucosal surface. However, confrary fo conventional wisdom, Heaney et al. (1990a) have demonstrated that solubility plays a limited role with the coingestion of food. Weaver and Liebman (2002) concede fhaf only... 

The aqueous boundary layer or the unstirred water layer (UWL) is a more or less stagnant layer, about 30-100 pm in thickness, composed of water, mucus, and glycocalyx adjacent to the intestinal wall that is created by incomplete mixing of the lumenal contents near the intestinal mucosal surface. The glycocalyx is made up of sulfated mucopolysaccharides, whereas mucus is composed of glycoproteins (mucin), enzymes. 

Rotaviruses are double-stranded wheel-shaped RNA viruses. These strains cause diarrhea by infecting the enterocyts of the villi in the small intestine. Changes to the villi include shortening of villus height, crypt hyperplasia, and mononuclear cell infiltration of the lamina propria. Diarrhea results from decreased absorption across intestinal mucosal surface. ... 

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. 

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

The food, now in a liquid form known as chyme, passes through the pyloric sphincter into the duodenum, where stomach acid is neutralized. There is wide variation in lengths of the components of the small intestine (i.e., duodenum, jejunum, and ileum) between individuals (Table 98-1). Most absorption of digested carbohydrate and protein occurs within the jejunum. Most fat absorption occurs within the jejunum and ileum. In the small bowel, breakdown of macronutrients (i.e., carbohydrate, protein, and fat) occurs both within the lumen of the gut and at the intestinal mucosal membrane surface. The absorptive units on the intestinal mucosal membrane are infoldings known as... 

K0/w as measured in the rat intestine [15,16], As with other examples that are available, as K0/w increases, the rate of absorption increases. One very extensive study [17-19] has examined in depth the physicochemical factors governing nonelectrolyte permeability for several hundred compounds. This study employed an in vitro preparation of rabbit gallbladder, an organ whose mucosal surface is lined by epithelial cells. The... 

Figure 2 (Left) Microscopic magnification (X46,500) of mucosal surface (S) associated with intestinal microvilli (V). (Right) Schematic of the microvilli illustrating the cytoskele-ton elements including junctional complexes. (From Ref. 76.)... 

H Daniel, G Rehner. Effect of metabolizable sugar on the mucosal surface pH of rat intestine. J Nutr 116 768-777, 1986. 

Laux, D. C., McSweegan, E. F., and Cohen, P. S. (1984). Adhesion of enterotoxigenic Escherichia coli to immobilized intestinal mucosal preparations A model of adhesion to mucosal surface components. /. Microbiol. Methods 2, 27-39. 

Following ingestion of the substance, the gastrointestinal (GI) tract is the site of initial or phase I toxicity to the mucosal surfaces. This toxicity is manifested by swelling, edema, and painful ulceration of the mouth, pharynx, esophagus, stomach, and intestine. With higher levels, other GI toxicity includes centrizonal hepatocellular injury, which can cause elevated bilirubin, and hepatocellular enzyme levels such as AST, ALT, and LDH. 

Crohn s disease is granulomatous and in most cases it is a simultaneous disease of the ileum and colon. The primarily inflamed region is the distal ileum, and all intestinal layers are thickened. The mucosal surface is reddened, nodular, and cobblestone-Uke, with mnltiple linear ulcerations. The mucosal layer is thickened by inflammatory infiltrate, the submucosa and serosa by fibrosis, and the serosa by hypertrophy. Chronic nlcerative colitis is a systemic disease that starts at the rectum or the sigmoid colon and progresses proximally to involve the entire left side of the colon. The colonic crypts are the first sites of cell damage and death, and the disease primarily involves the mucosal layer of the intestine. 

The products of lipid digestion—free fatty acids, 2-monoacylglycerol, and cholesterol—plus bile salts, form mixed micelles that are able to cross the unstirred water layer on the surface of the brush border membrane. Individual lipids enter the intestinal mucosal cell cytosol. 

In the intestine, saponins bind to mucosal cell membranes and change their physiology. Since the membranes of some cancer cells contain more cholesterol than do normal cells membranes [156], it is possible that saponins bind more to cancer cells and as a result induce their destruction. Since saponins are surface-active compounds that are not absorbed, their possible interaction with intestinal mucosal cell membranes must be emphasized. Because the average transit time of food is 24h, saponins can either in the intact or in the partly hydrolyzed form, remain in the intestine long enough to interact with free sterols and membrane lipids [157]. 

McNeil NI, Ling KL, Wager J. 1987. Mucosal surface pH of the large intestine of the rat and of normal and inflamed large intestine in man. Gut 28 707-713. 

Mestecky J, Russel MW, Elson CO Intestinal IgA Novel views on its function in the defence of the large mucosal surfaces. Gut 1999 44 2-5. 

In addition to the longitudinal pH gradient, there is a pH gradient starting with the lumen to the absorbing surface [109,110]. Because of this gradient, the pH at the mucosal surface of the small intestine is different from that of the luminal content (a decrease of at least 1 pH unit, e.g., from 7.1 to 6.1) [111,112]. It was shown that the acidic microclimate is an essential determinant in fatty acid uptake after micellization [113]. The presence of a low-pH compartment facilitates the dissociation of mixed micelles made up of taurocholate and oleic acid. The rate of fatty acid diffusion in the mucin layer was estimated to be 400% of that in a buffer solution [114]. 

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