EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



table 9.1. Permeability of Mammalian Muscle 



Capillaries to Lipid Insoluble Molecules 



* From smooth curves of figure 9.2. f Mols/sec/cm 2 



membrane per mol/ml concentration difference. The total 

 membrane surface in 100 g muscle, A m , is assumed to be 

 7000 cm 2 (281 ). t Calculated from over all bodily arterial 



disappearance curves (equation 8.1). 



of muscle (126, 232). Anatomical studies of visceral 

 capillaries also suggest a relatively high degree of 

 porosity (13). Exchange rates of lipid-insoluble mole- 

 cules between central nervous system tissue and blood 

 are far lower than in peripheral tissues (68, 185, 357) 

 although the anatomical site of the "blood-brain 

 barrier" has not been localized with certainty to the 

 capillary walls. Exchanges between blood and cere- 

 brospinal fluid are complicated by absorption in bulk 

 through large channels in the arachnoid villi and by- 

 specific active secretory mechanisms involving the 

 choroid plexuses and ependymal linings of the ven- 

 tricular system (279). 



In spite of these regional differences in capillary 

 permeability, it may be said that over-all bodily 

 capillary permeability, determined from arterial disap- 

 pearance rates of large molecules, does not differ 

 greatly from that of isolated muscle. For example, the 

 average plasma clearance (n/Ac) of a dextran fraction 

 of known free diffusion coefficient (D = 0.10 X io~ 5 

 cm 2 sec -1 , a = 32 A) was found by Grotte (126) to be 

 about .6 ml per min per kg dog or io -3 ml per sec 

 per 100 g tissue. From equation 7. 6, 



A S f> -3-5 5 



Xx" 2HT "*" D * ,0 +' x /0 --O/x 10 cm 



Application of the theory of restricted diffusion (equa- 

 tion 7.9) for average porosities of 40, 45, and 50 A 

 leads to true pore areas per unit path length of 1 .4, 0.5, 

 and 0.3 X io -5 cm per 100 g tissue, respectively. 



These values, pertaining to over-all bodily permeabil- 

 ity, may be compared with the value of 0.6 X io 5 cm 

 per 1 00 g tissue determined by the method of osmotic 

 transient in isolated muscle (Fig. 9.2). The close 

 correspondence between permeability to serum albu- 

 min computed from over-all arterial disappearance 

 curves on the one hand and restricted diffusion 

 through the capillaries of muscle on the other has 

 already been noted (table 9.1). Similarly, the over- 

 all bodily filtration coefficient is not greatly different 

 from that determined in intact extremities or isolated 

 perfused muscle (section 6). This correspondence be- 

 tween over-all capillary permeability and capillary 

 permeability determined in isolated muscle is not too 

 surprising since muscle accounts for some 65 per cent 

 of total body weight exclusive of skeleton and fat 

 which do not participate to a large extent in the capil- 

 lary exchange. 



IO. MOLECULAR SIEVING OF LARGE MOLECULES: 

 REGIONAL DIFFERENCES IN POROSITY 



In artificial systems it is possible to apply high pres- 

 sure differentials for rapid ultrafiltration, and under 

 these conditions even small molecules can be "sieved" 

 through porous membranes as illustrated in figure 

 7.4. In the capillary circulation, however, the trans- 

 membrane pressure differentials are necessarily small 

 and no appreciable steady-state concentration differ- 

 ences of small molecules can be maintained, even at 

 abnormally high rates of filtration. Substitution of 

 approximate value of A w /Ax and r in equation 7. 15 

 suggests that appreciable molecular sieving should be 

 detectable with molecules of radius 10 to 15 A at high 

 rates of filtration caused by venous occlusion. This 

 prediction has been verified in perfused hind limbs 

 for the case of inulin (a = 12-15 A) during net filtra- 

 tion at the rate of 0.2 ml per min per 100 g tissue. 

 Under these conditions the steady-state concentration 

 of inulin in capillary filtrate was found to be 70 per 

 cent of that in plasma (281); the theoretical value 

 calculated from equation 7.15 is 77 per cent. In the 

 case of still larger molecules, including the plasma 

 proteins, the restriction to diffusion becomes suffi- 

 ciently great to allow a high degree of molecular 

 sieving, even at normal filtration rates. 



Grotte (126) has carried out a detailed study of 

 molecular sieving in relation to steady-state concen- 

 trations of large molecules in leg lymph, liver lymph, 

 and cervical lymph. Grotte worked with dextran 

 polymers of known free diffusion coefficient and mo- 



