As well as being absorbed through the epithelial cells, molecules can pass through tissues via the intercellular or paracellular route through junctional gaps between cells. There has been much discussion regarding the importance of this process in transport across the gastrointestinal mucosa. There is considerable variation in the integrity of the tight junctions along the gastrointestinal tract, with the membranes of the stomach and large intestine having the highest transepithelial resistance. Norris and coworkers suggested that molecules with a greater molecular radius than 1.1 nm cannot permeate the intestinal paracellular space8. The pore size has been calculated to be 0.8 nm in the jejunum and 0.3 nm in the ileum and colon, so it unlikely that molecules of a significant size could be absorbed from the intestine by this route.
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