Mechanisms of intestinal adaptation: unstirred layer resistance and membrane transport

The effect of the resistance of unstirred water layers (UWL) on the kinetic parameters of active and passive intestinal transport processes is well established, but the possibility of adaptive changes in the resistance of this diffusion barrier in health and disease has only recently been appreciated. The rate of uptake (Jd) of a homologous series of saturated fatty alcohols into the jejunum is limited by diffusion through the UWL. The Jd of lauryl alcohol has been determined at different rates of stirring of the bulk phase, and at different sites along the intestine, in animals of different ages, in varying species, in rats with streptozotocin-induced diabetes mellitus, following abdominal irradiation, after acute and chronic exposure to ethanol, and after the feeding of various diets. The UWL varies in response to most of these experimental manipulations. After correcting for unstirred layer effects, the incremental change in free energy (integral of delta Fw----l) of the uptake of medium chain-length fatty acids and the maximal transport rate (Jmd) and Michaelis constant (Km) for glucose uptake were determined. These kinetic parameters changed in many of these experimental manipulations. However, there was no correlation between changes in UWL, integral of delta Fw----l, Jmd, Km or Jmd/Km. It is concluded that (1) the intestine is capable of adapting to a variety of physiological and pathological challenges; and (2) the major kinetic changes included UWL, integral of delta Fw----l, Jmd, and Km. The molecular mechanisms responsible for these changes in the dimensions and characteristics of the barriers to intestinal transport must now be defined.