TY - JOUR
T1 - Delineation of the dimensions and permeability characteristics of the two major diffusion barriers to passive mucosal uptake in the rabbit intestine
AU - Westergaard, H.
AU - Dietschy, J. M.
PY - 1974
Y1 - 1974
N2 - The rate of passive absorption into the intestinal mucosal cell is determined by at least 2 major diffusion barriers: an unstirred water layer and the cell membrane. This study defines the morphology and permeability characteristics of these 2 limiting structures. The unstirred water layer was resolved into 2 compartments: one behaves like a layer of water overlying the upper villi while the other probably consists 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 μm 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 barrier also was determined to vary with stirring rate and equaled only 2.4 cm2/100 mg in the unstirred condition but increased to 11.3 cm2/100 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 passively 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, define the thickness and area of the unstirred layer in the intestine and show that this barrier is rate limiting for the mucosal uptake of compounds such as fatty acids and cholesterol; in addition, the lipid membrane of the microvillus surface is shown to be a relatively polar structure.
AB - The rate of passive absorption into the intestinal mucosal cell is determined by at least 2 major diffusion barriers: an unstirred water layer and the cell membrane. This study defines the morphology and permeability characteristics of these 2 limiting structures. The unstirred water layer was resolved into 2 compartments: one behaves like a layer of water overlying the upper villi while the other probably consists 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 μm 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 barrier also was determined to vary with stirring rate and equaled only 2.4 cm2/100 mg in the unstirred condition but increased to 11.3 cm2/100 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 passively 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, define the thickness and area of the unstirred layer in the intestine and show that this barrier is rate limiting for the mucosal uptake of compounds such as fatty acids and cholesterol; in addition, the lipid membrane of the microvillus surface is shown to be a relatively polar structure.
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U2 - 10.1172/JCI107810
DO - 10.1172/JCI107810
M3 - Article
C2 - 4851286
AN - SCOPUS:0016289401
SN - 0021-9738
VL - 54
SP - 718
EP - 732
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -