ioi4 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



1.0 



8 



Cf _ [lymph] 



C, " [PLASMA] 



.6 - 



.2 - 



20 



30 



40 



50 



60 A 



fig. i o. i . Molecular sieving of dextrans in leg lymph 

 obtained from dogs. The results are in accord with the theory 

 of molecular sieving ^equation 7.15) through pores of radius 

 42 A and for molecules up to 32 A in radius. Increased lymph 

 flow induced by venous congestion produced the expected 

 increase in sieving. The unexpected passage of dextran mole- 

 cules exceeding 40 A in radius suggests an additional "large 

 pore" system estimated by Grotte to comprise 1/30,000 of the 

 total population of pores. [Adapted from Grotte (126).] 



lecular radius. Figure 10. 1, adapted from Grotte' 

 shows lymph : plasma concentration ratios as a func- 

 tion of molecular radius at two different lymph flows. 

 The theoretical curves for a capillary ultrafiltrate are 

 drawn from equation 7.15, assuming a pore radius of 

 42 A, that A w /Ax was constant and that capillary 

 filtration rate was proportional to observed lymph 

 flow. The agreement between theoretical and ob- 

 served concentration ratios is surprisingly good for 

 molecules up to about 32 A in radius. However, the 

 observed lymph concentrations of dextran molecules 

 ranging in size from 50 to 90 A cannot be explained 

 on the basis of molecular sieving through pores of 

 radius 42 A. In order to explain capillary permeabil- 



FIG. 10.2. Distribution of "leaks," "large pores" or gaps in 

 the walls of the minute vessels of frog's mesentery as indicated 

 by cinephotomicrographs of rapid, spotty passage of T-1824 

 (Evans blue dye). With camera running at the rate of 25 frames 

 per sec, the dye solution was perfused through the capillary 

 network from a micropipette introduced into the terminal, 

 feeding arteriole. From the film thus obtained single frames 

 have been removed to show sites and extent of dye passage at 

 intervals of seconds (e.g., 1", 2", 3", etc.) timed from that 

 frame in which the dye had first filled the capillaries (labeled 

 0). The frames labeled C show the network before dye entry; 

 those labeled 2' and C-» after the perfusion was ended to indicate 

 absence of stasis and hence absence of detectable injury. 



ity to these large molecules Grotte postulated the 

 existence of large capillary leaks, corresponding to 

 pores of radius 200 to 350 A but comprising only 1 

 part in 30,000 of the total population of pores as com- 

 puted by equation 7.16. In cervical lymph and liver 

 lymph the molecular sieving curve was shifted to the 

 right and the relative number of calculated capillary 

 leaks was increased to 1 in 20,000 and 1 in 340, re- 

 spectively. 



Concerning the locations of these leaks or large 

 pores along the length of the minute vessels very little 

 is known. There is some evidence, however, that they 

 may be more frequent in the walls of venous capillaries 

 and venules than in the walls of true capillaries. In 

 recent studies (Landis, unpublished) solutions of 

 T-1824 in Ringer's solution, with and without protein, 

 have been perfused by microinjection through single 

 vessels or through portions of peripheral networks in 

 the frog's mesentery. Motion pictures (25-40 frames 

 per sec) reveal sites at which the dye solutions pass 

 rapidly through the vessel wall during the first few 

 seconds of perfusion (fig. 10.2). In true capillaries the 

 loci of such early, spotty passage of dye are few in 

 number; the extravascular spots of dye are small in 

 size and distinct in outline. In venous capillaries and 

 venules the loci of passage are more numerous; the 

 extravascular spots of dye tend to be larger and, par- 

 ticularly around venules, often coalescent. It seems 

 likely, therefore, that while the small pore system is 

 uniformly distributed throughout the capillary net- 

 work, the leak or large pore system is more promi- 

 nent in the venous capillaries and venules. A differen- 

 tial distribution of this type helps explain earlier work 

 (reviewed in detail in ref. 207) on the spotty passage 

 of certain dyes through the walls of true capillaries 

 (200, 262) and on the gradient of permeability to 

 poorly diffusible dyes described by Rous and co- 

 workers (e.g., 161, 307, 308, 337, 338). 



Results similar to those obtained by Grotte (126) 



Left: perfusion of .01 M T-1824 freshly prepared in frog Ringer's 

 solution. Top section (magnification X 17) shows progression 

 of spotty passage involving true capillaries, a venous capillars' 

 and a minute venule. Middle and lower sections show greater 

 detail (magnification X 60) at 2 sec and 12 sec, respectively. 

 Right: perfusion of .01 M T-1824, ar 'd 3 g/100 mg albumin, in 

 frog Ringer's solution. Top section (magnification X 35) shows 

 spotty passage in true capillaries and a venous capillary. Middle 

 and lower sections show greater detail (magnification X 120) 

 at 2 sec and 12 sec, respectively. Rapid, spotty passage of per- 

 fused dye persisted despite protein binding. In general, how- 

 ever, protein binding made spots of passage more discrete. 



