io66 



IIWDBOOK OF PHYSIOLOGY 



CIRCULATION II 



consisting of gaps between mcsothelial cells caused by 

 pressure or, as suggested by Allen, by aspiration; 

 2) an intracellular pathway developed by infolding 

 of the plasma membrane around particles and the 

 subsequent pinching off of small pinocytic vesicles 

 (13a). This vesicular mechanism may be concerned 

 not only in transport from the exterior to the interior 

 of the cell but also in transport through cells by a 

 process termed cytopempsis (147a). The upper limit 

 to the size of particles which can be absorbed through 

 the extracellular route is probably determined by 

 the size of the meshes in the connective tissue layer 

 rather than by the potential openings between the 

 mesothelial or endothelial cells. Smaller particles may 

 travel through intercellular spaces in the roofs of 

 the lacunes where the mesothelial cells separate 

 from each other more readily than they do elsewhere. 

 Evidence that small particles take an extracellular 

 route through the lymphatic endothelium is perhaps 

 not so convincing, but that particles can enter the 

 interspace between lymphatic endothelial cells has 

 been conclusively shown by Palay & Karlin (163a) 

 in the central lacteal of an intestinal villus and by 

 Casley-Smith & Florey (39a) in their study on lym- 

 phatics in ears of mice and guinea pigs, colons of 

 rats, and diaphragms of mice. These authors suggest 

 the possibility that lymphatic endothelial cells in 

 general are less compactly joined than those in blood 

 capillaries and may separate from each other more 

 easily. The apparent absence of a continuous base- 

 ment membrane to lymphatic endothelium, as dis- 

 cussed above, may possibly facilitate this separation 

 of cells and be important in determining the perme- 

 ability of lymphatic endothelium to macromolecules 

 and particles traveling from without inward. 



If we accept the fact that two possible pathways, 

 intercellular and intracellular, are available for 

 movement of substances through lymphatic mem- 

 branes, their relative importance remains to be 

 determined. How, too, are we to explain the striking 

 difference between the ability of substances to enter 

 and to leave lymphatic vessels? Cunningham reviewed 

 the evidence available before 1926 and concluded 

 that the main pathway of absorption is intracellular. 

 Florey and his group, on the other hand, interpret 

 their more recent results with the electron microscope 

 as evidence of the possible greater importance of the 

 intercellular pathway. They (77a) point out that 

 there is no evidence that the greater permeability to 

 colloidal particles shown by lymphatic endothelium 

 when compared with blood capillary endothelium is 

 explained by a greater frequency of cytoplasmic 



vesicles. It is not too dfficult, perhaps, to accept the 

 point of view that the morphological basis of this 

 relatively high permeability of lymphatic endo- 

 thelium from without inward is related to cleavage 

 at intercellular junctions and absence of a well- 

 defined basement membrane. The available evidence 

 from varied sources, although not always direct or 

 definitive, is sufficient to suggest that mechanical 

 factors, pressure and concentration gradients, elastic- 

 ity of connective tissue, etc. (74a, 52a) may operate 

 to move these substances from the interstitial space. 

 Difficulty arises, however, in visualizing the same 

 process as operating from within outward. Peters 

 (171a) in 1935 appreciated this difficulty when he 

 attempted to formulate a comprehensive theory of 

 lymphatic absorption and raised the question as to 

 how one could expect to hold water in a sieve by 

 putting a valve at its mouth. Admittedly we still do 

 not have sufficient information to provide an over-all 

 sophisticated concept of permeability of lymphatic 

 vessels. For the time being, it may therefore be 

 wise to consider the following simple concept. We 

 believe it to be consistent with the available evidence 

 and to offer an explanation of the apparent one-way 

 flow of materials into but not out of the lymphatics. 

 Lacking evidence to the contrary, we may assume 

 that the smallest terminal lymphatic capillaries are 

 freely permeable to small and large molecules and 

 particles moving in either direction through inter- 

 cellular gaps. Compression of these vessels in any 

 manner will force their contents in all directions. 

 Some of the contents can, however, be forced centrally 

 into larger vessels and ducts. The valves in these 

 vessels will prevent backflow. Once the lymph 

 reaches the larger vessels, it no longer loses its macro- 

 molecules and particles, since the walls of the larger 

 vessels, as previously discussed, restrict molecules 

 larger than molecular weight of approximately 2000 

 (at least in the dog). 



This simple concept implies a relatively inept and 

 inefficient system, a "leaky pump" system about 

 which Peters complained. As Allen commented, 

 however, a leaky pump will still pump, and as 

 Drinker emphasized, the lymphatic system is, in the 

 final analysis, a rather casual system. It does a 

 reasonably good job under "normal" conditions. Its 

 ineffectiveness becomes manifest chiefly under patho- 

 logical situations. This aspect of the functions of the 

 lymphatic system, its inadequacy in various patho- 

 logical situations, will continue to merit careful 

 study. 



