Absorption physiology

Ciypt and Villus Structures of the Mucosa of the Small Intestine 

Cell division and the subsequent differentiation give rise to several different types of cells, including the enterocyte and goblet cells. Other types that account for only about 1,0% of the epithelial ceils of the gut include endocrine cells, which produce hormones, and Paneth cells, which produces lysozyme, an antibacterial enzyme. The reason for the rapid turnover of the epithelial surface of the gut is the necessity of maintaining its function in the harsh environment of pancreatic enzymes. 

Another nutritional issue concerns the crypts. Certain bacterial and viral infections can provoke vast increases in the secretory activity of the crypts, resulting in excessive losses of salts and water, as well as diarrhea. Secretory diarrheas that continue for a week or longer may be life threatening, as discussed in Chapter 10 in the section on Sodium, Potassium, and Water. 

Adequate dietary intakes of sodium and chloride for the adult are estimated to be 1.1-1.3 and t.7-5.1 g per day, respectively. These dietary salts are needed to replace obligatory losses in the urine and small losses in the sweat. Most of the sodium and chloride ions in the diet are absorbed by the jejunum and ileum only about 5% is lost in the fcccs. 

FIGURE 2,50 Crypts and viltus, (Left) A normal crypt and villus. Two crypts aie shown on either side of the villus. Maiabsnrptive diseases may involve degeneration of the vilb. (Cettier) A short villus. Complete disappearance of a villus. The disease may involve 

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Although the pH-partition hypothesis and the absorption potential concept are useful indicators of oral drug absorption, physiologically based quantitative approaches need to be developed to estimate the fraction of dose absorbed in humans. We can reasonably assume that a direct measure of tissue permeability, either in situ or in vitro, will be more likely to yield successful predictions of drug absorption. Amidon et al. [30] developed a simplified film model to correlate the extent of absorption with membrane permeability. Sinko et al. [31] extended this approach by including the effect of solubility and proposed a macroscopic mass balance approach. That approach was then further extended to include facili-... 

Drug delivery systems. 2. Drugs—Dosage forms. 3. Drugs—Physiological transport. 4. Absorption (Physiology) I. Touitou, Elka, 1942- II. Barry, Brian W., 1939-... 

P. Tso, Intestinal lipid absorption, Physiology of the Gastrointestinal Tract (L. R. Johnson, chief ed.), Raven Press, New York, 1994, pp. 1867-1908. 

Staidtes and Other Poly.saocha rides Used by the Food Industry Hirzymes Used to Ingest Carbohydrates Absorption of Carbohydrates SpeciaE Topic Sugar Transporters Issues in Carbohydrate Nutrition Absorption Physiology... 

In this chapter, the principles and practices related to the successful use of EN support are described. Digestive and absorptive physiology is reviewed and the beneficial effects of EN are presented. The indications for EN, and descriptions of various enteral access and administration methods are also summarized. Characteristics of... 

Toxicity. Fluoroborates are excreted mostly in the urine (22). Sodium fluoroborate is absorbed almost completely into the human bloodstream and over a 14-d experiment all of the NaBF ingested was found in the urine. Although the fluoride ion is covalently bound to boron, the rate of absorption of the physiologically inert BF from the gastrointestinal tract of rats exceeds that of the physiologically active simple fluorides (23). 

Pharmacodynamics is the study of dmg action primarily in terms of dmg stmcture, site of action, and the biochemical and physiological consequences of the dmg action. The availabiUty of a dmg at its site of action is deterrnined by several processes (Fig. 1), including absorption, metaboHsm, distribution, and excretion. These processes constitute the pharmacokinetic aspects of dmg action. The onset, intensity, and duration of dmg action are deterrnined by these factors as well as by the avadabihty of the dmg at its receptor site(s) and the events initiated by receptor activation (see Drug delivery). 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

The realization of sensitive bioanalytical methods for measuring dmg and metaboUte concentrations in plasma and other biological fluids (see Automatic INSTRUMENTATION BlosENSORs) and the development of biocompatible polymers that can be tailor made with a wide range of predictable physical properties (see Prosthetic and biomedical devices) have revolutionized the development of pharmaceuticals (qv). Such bioanalytical techniques permit the characterization of pharmacokinetics, ie, the fate of a dmg in the plasma and body as a function of time. The pharmacokinetics of a dmg encompass absorption from the physiological site, distribution to the various compartments of the body, metaboHsm (if any), and excretion from the body (ADME). Clearance is the rate of removal of a dmg from the body and is the sum of all rates of clearance including metaboHsm, elimination, and excretion. 

Anthropologic features of humans, their physical activities, ventilation capacities, and the state of their circulation all affect exposure to chemical compounds. Some of the physiological determinants of exposure will be dealt with below. Exercise typically increases cardiac output, facilitates circulation, increases the minute volume of ventilation, is associated with vasodilation of the skin circulation, and increases perspiration and secretory activity of the sweat glands. All of these changes tend to facilitate the absorption of chemicals through multiple routes. 

Absorption, distribution, biotransformation, and excretion of chemical compounds have been discussed as separate phenomena. In reality all these processes occur simultaneously, and are integrated processes, i.e., they all affect each other. In order to understand the movements of chemicals in the body, and for the delineation of the duration of action of a chemical m the organism, it is important to be able to quantify these toxicokinetic phases. For this purpose various models are used, of which the most widely utilized are the one-compartment, two-compartment, and various physiologically based pharmacokinetic models. These models resemble models used in ventilation engineering to characterize air exchange. 

Physiologically based toxicokinetic models are nowadays used increasingly for toxicological risk assessment. These models are based on human physiology, and thus take into consideration the actual toxicokinetic processes more accurately than the one- or two-compartment models. In these models, all of the relevant information regarding absorption, distribution, biotransformarion, and elimination of a compound is utilized. The principles of physiologically based pharmaco/ toxicokinetic models are depicted in Fig. 5.41a and h. The... 

Physical detection methods are based on inclusion of substance-specific properties. The most commonly employed are the absorption or emission of electromagnetic radiation, which is detected by suitable detectors (the eye, photomultiplier). The / -radiation of radioactively labelled substances can also be detected directly. These nondestructive detection methods allow subsequent micropreparative manipulation of the substances concerned. They can also be followed by microchemical and/or biological-physiological detection methods. 

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