Passage of molecules through capillary wals.

F ROM THE POINT OF VIEW of hemodynamics the blood is generally considered to circulate within a closed system of blood vessels. Even the smallest capillaries appear, under the microscope, as closed thin-walled vessels separating the blood from the extravascular fluid. Only occasionally are discontinuities in the capillary wall made evident by the diapedesis of one of the formed elements of the blood and even in such cases it is hard to be certain that a microscopically visible channel of egress is present. At high magnifications the blood appears to flow rapidly through individual capillaries thus forming a striking contrast to the relatively stagnant extravascular fluid and accentuating the role of the capillary membrane in providing a phase boundary separating the blood from the tissues. There are good reasons for supposing, however, that the capillary blood is in intimate contact with extravascular fluid and that the visible flow of blood through the capillaries is, in fact, very small in comparison with the intiWe flow of water and dissolved materials back and forth through the capillaxy walls. Evidence to be reviewed below suggests that this invisible component of the circulation takes place at a rate which is many times greater than that of the entire cardiac output. Indeed, it is by means of this ‘ultramicroscopic circulation’ through the capillary wall that the circulatory system as a whole fulfills its ultimate function in the transport of materials to and from the cells of the body. This review will deal with the physical properties of the ultramicroscopic circulation, its functional structure, the magnitude of flow through it and the physicochemical mechanisms regulating the flow. Direct methods for the study of ultrastructure have not as yet been applied to the capillary wall and much of what can be said must be deduced from quantitative studies of capillary permeability. A wealth of evidence supports the view that the exchange of materials through the walls of living capillaries takes place by physical processes which involve no expenditure of energy on the part of the capillary endothelial cells themselves. This evidence has been reviewed previously (20,30, 89, 162) and need not be considered here in detail. At least two types of capillary structure appear to be involved. On the one hand we have to consider the permeability characteristics of the plasma membranes which envelop the protoplasm of the capillary endothelial cells and which comprise the greater part of the visible capillary surface. On the basis of analogy with other known plasma membranes we may expect this type of structure to exhibit a relatively low order of permeability to ions and lipid insoluble molecules and a high order of permeability to oqgen, carbon dioxide and other lipid soluble substances. On the other hand, we have to consider specialized regions through or between endothelial cells which endow the capillary wall as a whole with a relatively high, degree of permeability to water, ions and large lipid insoluble molecules. This type of permeability resembles that of artificial porous membranes and has given rise to the hypothesis that the blood communicates directly with the extravascular fluid via channels or