Md. Levitt et al., USE OF MALTOSE HYDROLYSIS MEASUREMENTS TO CHARACTERIZE THE INTERACTION BETWEEN THE AQUEOUS DIFFUSION BARRIER AND THE EPITHELIUM IN THE RAT JEJUNUM, The Journal of clinical investigation, 97(10), 1996, pp. 2308-2315
Rates of intestinal absorption and surface hydrolysis are determined b
y the interaction of two barriers: poorly stirred fluid adjacent to th
e mucosa, and the epithelial cell, These two barriers commonly are mod
eled as a fixed, flat layer of epithelium covered by a fixed thickness
of unstirred fluid. To more accurately simulate these barriers in a v
illous mucosa, maltase activity (measured in vitro) was distributed ov
er an anatomically correct model of rat jejunal villi. We then determi
ned what interaction of the aqueous and epithelial barriers best predi
cted in vivo maltose hydrolysis rates measured over a broad range of i
nfusate concentrations. Hydrolysis was accurately predicted by a model
in which unstirred fluid extended from 20 mu m over the villous tips
throughout the intervillous space. In this model, the depth of diffusi
on into the intervillous space is inversely proportional to the effici
ency of epithelial handling of the solute. As a result, both the aqueo
us barrier and the functional surface area are variables rather than c
onstants, Some implications of our findings (relative to the conventio
nal model) include: higher predicted V-max, efficient handling of low
concentrations of a solute at the villous tips while high concentratio
ns must penetrate thick aqueous barriers, and sensitive regulation of
transport rates via ease of access to the intervillous space. (J. Clin
. Invest. 1996. 97:2308-2315.)