A B S T R A C T The present studies were designed to characterize sodium transport in the jejunum and ileum of humans with respect to the effects of water flow, sodium concentration, addition of glucose and galactose, and variations in anionic composition of luminal fluid. In the ileum, sodium absorption occurred againstvery steep electrochemical gradients (110 mEq/liter, 5-15 mv), was unaffected by the rate or direction of water flow, and was not stimulated by addition of glucose, galactose, or bicarbonate. These findings led to the conclusion that there is an efficiently active sodium transport across a membrane that is relatively impermeable to sodium. In contrast, jejunal sodium (chloride) absorption can take place against only the modest concentration gradient of 13 mEq/ liter, was dramatically influenced by water movement, and was stimulated by addition of glucose, galactose, and bicarbonate. The stimulatory effect of glucose and galactose was evident even when net water movement was inhibited to zero by mannitol. These observations led to the conclusion that a small fraction of jejunal sodium absorption was mediated by active transport coupled either to active absorption of bicarbonate or active secretion of hydrogen ions. The major part of sodium absorption, i.e. sodium chloride absorption, appeared to be mediated by a process of bulk flow of solution along osmotic pressure gradients. The stimulatory effect of glucose and galactose, even at zero water flow, was explained by a model in

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Relatively little information is available concerning the membrane structure of the mucosal cells of the small intestine. Hdber and Hober (1) and Schanker, Tocco, Brodie, and Hogben (2, 3) studied the absorption of a variety of substances in rats and found that absorption rate increased as lipid solubility increased. From this it has been deduced that mucosal cell membranes are lipoid in nature and that lipid-soluble substances are absorbed by dissolving in the cell membrane. However, it has been known for many years that small molecules, although lipid insoluble, can also be absorbed from the gastrointestinal tract. This has led to the hypothesis that, although essentially lipoidal, cell membranes are interspersed with water-filled pores, through which small molecules can diffuse. Hbber and Hdber (1) tested this hypothesis in the small intestine of the rat by correlating the absorption rate of nonlipid-soluble substances with their molecular size. Their results support the thesis that these molecules are absorbed by diffusion through water-filled pores, since small molecules were absorbed more rapidly than larger ones, and beyond a certain size (molecular weight about 180, which corresponds to a molecular radius of about 4 A) no penetration occurred. Lindemann and Solomon's studies (4) are in close agreement, since they experimentally determined, by an independent method, the pore radius of the luminal surface of the rat jejunal cells to be approximately 4 A. This is the only available estimate of intestinal pore size in any species. and no estimates at all are available for pore size at different levels of the small intestine.The purpose of our studies, therefore, was to evaluate the permeability of the human intestinal mucosa by measuring the effective pore size at different levels of the small intestine. The theoretical basis for the present studies rests on the demonstration by Staverman (5) and Solomon (6) that the ability of a nonlipid-soluble solute to exert an effective osmotic pressure gradient 1 across a membrane is a function of its molecular radius relative to the radius of the water-filled pores in that membrane. Thus, the degree to which a solute of known molecular size is capable of exerting its full theoretic osmotic pressure gradient, which is defined as the reflection coefficient (a), can be used to calculate the pore size of the membrane, which. in turn, determines the permeability of the membrane to nonlipid-soluble solutes.To

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Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ > H+ > Ca2+ > Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.

A B S T R A C T Using a triple-lumen constant perfusion system, the following observations were made in normal subjects. First, chloride, bicarbonate, and sodium were found to exhibit net movement across ileal mucosa against electrochemical gradients. Second, during perfusion with a balanced electrolyte solution simulating plasma, the ileum generally absorbed, but sometimes secreted fluid. A reciprocal net movement of chloride and bicarbonate was noted when sodium movement was zero. Increasing rates of sodium absorption were associated with decreasing bicarbonate secretion rates and finally bicarbonate absorption. Even when bicarbonate was absorbed ileal contents were alkalinized (by contraction of luminal volume). Third, net chloride movement was found to be sensitive to bicarbonate concentration in ileal fluid. For instance, chloride was absorbed from solutions containing 14 or 44 mEq/liter of bicarbonate, but was secreted when ileal fluid contained 87 mEq/liter of bicarbonate. Fourth, when chloridefree (sulfate) solutions were infused, the ileum absorbed sodium bicarbonate and the ileal contents were acidified. Fifth, when plasma-like solutions were infused, the potential difference (PD) between skin and ileal lumen was near zero and did not change when chloride was replaced by sulfate in the perfusion solution.These results suggest that ileal electrolyte transport occurs via a simultaneous double exchange, Cl/HCOs and Na/H. In this model neither the anion nor the cation exchange causes net ion movement; net movement results from the chemical reaction between hydrogen and bicarbonate. No other unitary model explains all of the following observations: (a) human ileal transport in vivo is essentially nonelectrogenic even though Na, Cl, and HCO3 are transported against electrochemical Dr. Turnberg's present address is Manchester Royal Infirmary, Oxford Road, Manchester 13, England.

The purpose of this study was to measure magnesium absorption over the wide range of intakes to which the intestine may be exposed from food and/or magnesium-containing medications. Net magnesium absorption was measured in normal subjects after they ingested a standard meal supplemented with 0, 10, 20, 40, and 80 mEq of magnesium acetate. Although absorption increased with each increment in intake, fractional magnesium absorption fell progressively (from 65% at the lowest to 11% at the highest intake) so that absorption as a function of intake was curvilinear. This absorption-intake relationship was almost perfectly represented by an equation containing a hyperbolic function plus a linear function. Our results are statistically compatible with a magnesium absorption process that simultaneously uses a mechanism that reaches an absorptive maximum, plus a mechanism that endlessly absorbs a defined fraction (7%) of ingested magnesium. Compared to previous studies of calcium absorption, much less magnesium than calcium was absorbed at intakes above 8 mEq/meal, apparently due to greater restriction of intestinal permeability to magnesium. We also found that magnesium from a high magnesiumcontaining food source, almonds, was just as bioavailable as from soluble magnesium acetate. In contrast, magnesium absorption from commercially available enteric-coated magnesium chloride was much less than from magnesium acetate, suggesting that enteric coating can impair magnesium bioavailability. (J. Clin. Invest. 1991.88:396-402.)

The purpose of these studies was to gain insight into the pathophysiology of pure osmotic diarrhea and the osmotic diarrhea caused by carbohydrate malabsorption.