1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions.

2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose.

3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.

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