Delineation of the dimensions and permeability characteristics of the two major diffusion barriers to passive mucosal uptake in the rabbit intestine

ABSTRA CT The rate of passive absorption into the intestinal mucosal cell is determined by at least two major diffusion barriers: an unstirred water layer and the cell membrane. This study defines the morphology and permeability characteristics of these two limiting structures. The unstirred water layer was resolved into two compartments: one behaves like a layer of water overlying the upper villi while the other probably con-sists of solution between villi. The superficial layer is physiologically most important during uptake of highly permeant compounds and varies in thickness from 115 to 334 Am as the rate of mixing of the bulk mucosal solution is varied. From data derived from a probe molecule whose uptake was limited by the unstirred layer, the effective surface area of this diffusion bar-rier also was determined to vary with stirring rate and equaled only 2.4 cm ' 100 mg- ' in the unstirred con-dition but increased to 11.3 cm ' 100 mg- ' with vigorous mixing. This latter value, however, was still only 1/170 of the anatomical area of the microvillus membrane. With these values, uptake rates for a number of pas-sively absorbed probe molecules were corrected for unstirred layer resistance, and these data were used to calculate the incremental free energy changes associated with uptake of the-CH2- (- 258 cal mol'),-OH (+ 564), and taurine (+ 1,463) groups. These studies, then, have defined the thickness and area of the un-A portion of this work was presented before the Ameri-can Federation for Clinical Research and is reported in abstract form in Clin. Res. 20: 736, 1972. Dr. Westergaard was a postdoctoral fellow in Gastroen-terology while these studies were undertaken. His curren