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

Summary. Water and electrolyte movement in the jejunum of normal subjects and patients with sprue was measured during perfusion with isotonic electrolyte solutions. Normal subjects absorbed water, sodium, and potassium. By contrast, in patients with sprue (seven with adult celiac sprue and one with tropical sprue) who had diarrhea and steatorrhea, these substances were secreted into the intestinal lumen. This indicates that the jejunal mucosa of these patients was in a secretory state with respect to water and electrolytes.A method is presented for detecting abnormalities in the effective pore size in disease states. The method is based on the principle of restrictive diffusion and involves measuring the simultaneous diffusion rates of solutes of different molecular size. Since the method does not depend on measurement of water flow in response to osmotic pressure gradients, it can be used in disease states in which absorption and secretory processes involving water may be abnormal.The ratio of urea to tritiated water diffusion in the jejunum of normal subjects averaged 0.8, compared to 0.2 in patients with sprue. This indicates a marked decrease in the effective pore size of the jejunal mucosa in sprue. This conclusion was strengthened by the finding that erythritol and L-xylose, which are somewhat larger solutes than urea, are essentially nonabsorbable in small bowel involved with sprue. IntroductionMalabsorption of water and electrolytes is a well-known feature of sprue. It is not clear, however, whether this is due simply to decreased mucosal surface area of small bowel mucosa, or whether specific alterations of permeability and transport processes are also involved. The development of intestinal perfusion techniques offers a means for studying this problem.