Classic Pages
JOHN R. PAPPENHEIMER
Passage of molecules through capillary walls
Physiological Reviews, vol. 33, pp. 387-423, 1953
416
JOHN K. PAPPENHEIMER
Volume 33
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antipyrine derivatives were found to be related to the temperature coefficients of
their lipid solubilities rather than to their aqueous diffusion coefficients.
These results indicate that lipid-soluble molecules can diffuse through regions in
the capillary wall which are relatively impermeable to lipid-insoluble molecules.
The permeability characteristics of this additional pathway are similar to those of
cell membranes in general. It seems reasonable, therefore, to identify the diffusion
pathway for lipid-soluble molecules with the plasma membranes of the capillary
endothelia! cells themselves, as opposed to the system of water-filled pores penetrating through or between these cells, which is capable of accounting for the passage of water and lipid-insoluble molecules.
CONCLUSION
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Our scientific senses have sharpened considerably since these words were written. Yet, we must admit, in this year 1953, that no means are available to visualize
the channels ('infinite in number') which subserve the ultimate function of the circulatory system in the transport of materials to and from the cells.
In this review I have attempted to combine the facts of capillary permeability
with theory and fact from physical chemistry, to form some crude estimate of the
number and dimensions of these pathways, the magnitude of flow through them and
the physical mechanisms which regulate the flow. The picture which has emerged
may be summarized as follows, choosing the capillary bed in mammalian extremities
as a quantitative example.
The passage of water and lipid-insoluble molecules takes place through aqueous
channels or pores penetrating the capillary wall. The total cross-sectional area of
the pores comprises less than 0.2 per cent of the histological surface of the capillaries
and may well be limited to areas between endothelial cells as suggested by Chambers
and Zweifach (20).
Uniform cylindrical pores of radius 30 to 45 A and a population density of 1-2 X
10* per cm.! of capillary wall would account for the observed rates of passage of
water and lipid-insoluble molecules of various sizes. However, there are no reasons
for supposing that the channels are actually cylindrical and we may regard this value.
of 'effective' pore radius as analogous to the Einstein-Stokes molecular radius which,
by itself, tells nothing of the actual shape of the molecule. Net volume flow of fluid
through these channels takes place by hydrodynamic processes. Under normal arcumstances the transport of materials by hydrodynamic flow (filtration and absorption) is extremely slow, the rate of fluid movement being something less than 2 per
cent of the plasma flow. Diffusion, rather than hydrodynamic flow, constitutes the
chief process whereby small molecules can exchange rapidly between blood plasma
and interstitial fluid. The diffusion of water, NaCl, urea and glucose in both directions through the capillary wall occurs at rates estimated to be, respectively, 80, 40,
30 and 10 times the rates at which these substances are brought to the tissues by
the incoming blood. These high rates of exchange occur in spite of the small pore
area, the chief structural factor concerned being the short path length for diffusion
After carefully delineating the physical processes involved and examining the available physiological
evidence, Pappenheimer presented his pore theory of capillary permeability.
Classic Pages
Circ Res. 1969;25:106
doi: 10.1161/01.RES.25.2.106
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Copyright © 1969 American Heart Association, Inc. All rights reserved.
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