HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



kidney or 5 to 10 per cent of the available glomerular 

 surface estimated histologically by Vimtrup (360). 



Recent studies of glomerular ultrastructure suggest 

 that the anatomical basis for glomerular sieving is not 

 in the fenestrated capillary endothelium, but rather 

 in the epithelial cells (podocytes) covering glomerular 

 capillaries. According to Hall (141) these cells form 

 foot processes which approximate the endothelial 

 basement membranes in such fashion as to form inter- 

 cligitating "slit-pores" which appear to be 80 to 100 A 

 wide and occupy 2 to 3 per cent of the total surface. 



ii. capillary permeability to lipid-soluble 

 molecules; respiratory gases 



Capillary permeability to lipid-soluble molecules 

 has been studied by Renkin (296, 297) using the per- 

 fused hind-limb preparation. Urethan (mol wt 89), 

 paraldehyde (mol wt 132) and triacetin (mol wt 218) 

 traversed the capillary walls so rapidly that no os- 

 motic transients were detectable (figure 11.1). Glyc- 

 erol and acetic esters of glycerol were shown to pass 

 through capillary walls at high rates which varied in 

 order of their oil : water partition coefficients but in 

 order opposite to that expected on the basis of their 

 aqueous diffusion coefficients. The temperature co- 

 efficients of capillary permeability to antipyrine and 

 antipyrine derivatives were found to be related to the 

 temperature coefficients of their lipid solubilities 

 rather than to their aqueous diffusion coefficients. 



These results suggest that lipid-soluble molecules 

 can diffuse through regions in the capillary wall 

 which are relatively impermeable to lipid-insoluble 

 materials. The permeability characteristics of this 



additional pathway are similar to those of cell mem- 

 branes in general. It seems logical, therefore, to iden- 

 tify the diffusion pathway for lipid-soluble molecules 

 with the plasma membranes of the capillary endothe- 

 lial cells themselves, as opposed to the system of 

 water-filled pores penetrating through or between 

 these cells, which is capable of accounting for passage 

 of water and lipid-insoluble molecules. 



The respiratory gases have relatively large oil: 

 water partition coefficients (212) and may therefore 

 be expected to utilize the entire endothelial surface 

 for the transcapillary diffusion process. Recent meas- 

 urements of pulmonary diffusing capacity (306) indi- 

 cate that permeability of human alveolar mem- 

 branes (alveolar capillaries plus alveolar epithelium) 

 is approximately 60 ml 2 per min per mm Hg O2 

 pressure difference. In terms of oxygen concentration 

 difference, this value becomes 0.4 X io 5 cm 3 sec -1 

 (i.e., ml/sec, ml/ml concentration difference). The 

 capillary surface area in the lungs is approximately 

 4 X 10 s cm' 2 (258), whence the specific permeability 

 coefficient for oxygen is 10,000 X io~ B cm sec -1 . This 

 value may be compared with 23 X io~ 5 cm sec -1 , 

 representing the specific permeability of muscle capil- 

 laries to water (table 9.1). Presumably the greater 

 permeability to oxygen is a result of lipid solubility, 

 since the pulmonary capillaries resemble peripheral 

 capillaries in being relatively impermeable to small 

 lipid-insoluble molecules (378). In 100 g of quiescent 

 muscle containing a capillary surface area of 5,000- 

 10,000 cm 2 the steady-state flow of oxygen across the 

 capillary walls is about 0.4 ml per min (fig. 12.2). 

 During maximal muscular activity the oxygen re- 

 quirements increase 20-fold to 30-fold and the avail- 

 able capillary surface may increase 2-fold to 4-fold. 



fig. 1 1.1. Osmotic transients produced by 

 urethan and urea in an isolated perfused cat 

 hind limb. pCi = isogravimetric capillary 

 pressure. P v = protein osmotic pressure in 

 perfusion fluid. 36 msi/liter of urea produced 

 a large osmotic transient owing to restricted 

 diffusion of urea through the capillary walls. 

 Urethan, despite its larger molecular size, 

 failed to produce a detectable osmotic effect. 

 The results are attributed to the greater lipid 

 solubility of urethan which enables it to diffuse 

 through the entire capillary endothelial 

 surface. [From Renkin (296 1.] 



pCi 

 or 



PP 



mm 



H* 



25 



20 



15 



1 



T 



pp 



URETHAN 

 36mM/l 



°«t>-c>J 



-I-"- 



UREA 



+ 

 URETHAN 

 36 mM/1 of each 



UREA 

 36mM/l 



80 100 120 140 160 180 200 220 



TIME, MINUTES AFTER START OF PERFUSION 



240 



