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

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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A rare syndrome has been described in which mineralocorticoid-resistant hyperkalemia of renal origin occurs in the absence of glomerular insufficiency and renal sodium wasting and in which hyperchloremic acidosis, hypertension, and hyporeninemia coexist. The primary abnormality has been postulated to be a defect of the potassium secretory mechanism of the distal nephron. The present studies were carried out to investigate the mechanism of impaired renal potassium secretion in a patient with this syndrome. When dietary intake of sodium chloride was normal, renal clearance of potassium was subnormal (CK/GFR = 3.6 +/- 0.2%; normal subjects, 9.0 +/- 0.9%, N = 4) despite high normal or supernormal levels of plasma and urinary aldosterone. The fractional clearance of potassium remained subnormal (CK/GFR = 5.1 +/- 0.2%) during superimposed chronic administration of superphysiologic doses of mineralocorticoid hormone. Little increase in renal potassium clearance occurred when the delivery of sodium to distal nephron segments was increased further by the i.v. infusion of sodium chloride, despite experimentally sustained hypermineralocorticoidism. But potassium clearance increased greatly when delivery of sodium to the distal nephron was increased by infusion of nonchloride anions: sulfate (sodium sulfate infusion, low sodium chloride diet; CK/GFR = 63.7 +/- 0.4%) or bicarbonate (sodium bicarbonate plus acetazolamide infusion; CK/GFR = 81.7 +/- 1.7%). These findings indicate that mineralocorticoid-resistant renal hyperkalemia in this patient cannot be attributed to the absence of a renal potassium secretory capability or to diminished delivery of sodium to distal nephron segments; instead it may be dependent on chloride delivery to the distal nephron. We suggest that the primary abnormality in this syndrome increases the reabsorptive avidity of the distal nephron for chloride, which (1) limits the sodium and mineralocorticoid-dependent voltage driving force for potassium and hydrogen ion secretion, resulting in hyperkalemia and acidosis and (2) augments distal sodium chloride reabsorption resulting in hyperchloremia, volume expansion, hyporeninemia, and hypertension.

Using a constant perfusion technique, sodium and bicarbonate absorption was studied in human subjects. The following observations were made on sodium absorption from saline solution: (a) the rate of sodium absorption is markedly influenced by bulk water flow, (b) when net water flow is zero, sodium absorption is zero if there are no concentration gradients between plasma and lumen that favor net NaCl diffusion; and (c) the PD between abraded skin and jejunal lumen is near zero when saline is perfused and does not change with partial substitution of sulfate or bicarbonate for chloride. Based on these observations, we conclude that sodium absorption from saline is entirely passive in the human jejunum. On the other hand, in the presence of bicarbonate sodium is absorbed actively against electrochemical gradients. The mechanism of the link between bicarbonate and sodium absorption was studied in normal subjects and in 11 patients with pernicious anemia; the latter were chosen because they do not secrete gastric acid which can react with bicarbonate in the jejunal lumen. We observed that bicarbonate absorption (a) occurs against steep electrochemical gradients, (b) does not generate a potential difference between abraded skin and jejunal lumen, (c) is inhibited by acetazolamide, and (d) generates a high CO2 tension in jejunal fluid. These observations suggest that bicarbonate absorption is mediated by active hydrogen secretion, rather than by bicarbonate ion transport per se, and that the link between sodium and bicarbonate transport is best explained by a sodium-hydrogen exchange process.