There are three basic mechanisms by which substances move across the capillary walls in most organs and tissues to enter or leave the interstitial fluid: diffusion, vesicle transport, and bulk flow. Mediated transport constitutes a fourth mechanism in the capillaries of the brain. Diffusion and vesicle transport are described in this section, and bulk flow in the next. In all capillaries, excluding those in the brain, diffusion constitutes the only important means by which net movement of nutrients, oxygen, and metabolic end products occurs across the capillary walls. As described in the next section, there is some movement of these substances by bulk flow, but the amount is negligible. Lipid-soluble substances, including oxygen and carbon dioxide, easily diffuse through the plasma membranes of the capillary endothelial cells. In contrast, ions and polar molecules are poorly soluble in lipid and must pass through small water-filled channels in the endothelial lining.
The presence of water-filled channels in the capillary walls causes the permeability of ions and small polar molecules to be quite high, although still much lower than that of lipid-soluble molecules. One location of these channels is the intercellular clefts—that is, the narrow water-filled spaces between adjacent cells. Another set of water-filled channels is provided by the fusedvesicle channels that penetrate the endothelial cells. The water-filled channels allow only very small amounts of protein to diffuse through them. Very small amounts of protein may also cross the endothelial cells by vesicle transport—endocytosis of plasma at the luminal border and exocytosis of the endocytotic vesicle at the interstitial side. Variations in the size of the water-filled channels account for great differences in the "leakiness" of capillaries in different organs. At one extreme are the "tight" capillaries of the brain, which have no intercellular clefts, only tight junctions. Therefore, water-soluble substances, even those of low molecular weight, can gain access to or exit from the brain interstitial space only by carriermediated transport through the blood-brain barrier.
At the other end of the spectrum are liver capillaries, which have large intercellular clefts as well as large holes in the plasma membranes of the endothelial cells so that even protein molecules can readily pass across them. This is very important because two of the major functions of the liver are the synthesis of plasma proteins and the metabolism of substances bound to plasma proteins. The leakiness of capillaries in most organs and tissues lies between these extremes of brain and liver capillaries. What is the sequence of events involved in transfers of nutrients and metabolic end products between capillary blood and cells? Nutrients diffuse first from the plasma across the capillary wall into the interstitial fluid, from which they gain entry to cells. Conversely, metabolic end products from the tissues move across the cells’ plasma membranes into interstitial fluid, from which they diffuse across the capillary endothelium into the plasma.