EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



999 



though stepwise increases of proteinuria occurred 

 after that. Pappenheimer found (unpublished studies) 

 in the perfused cat's leg by the isogravimetric method 

 that cyanide did not, under certain conditions, 

 increase either the filtration coefficient or the per- 

 meability of the capillary wall to protein. This raises 

 the interesting possibility that any effects which severe 

 hypoxia may have on capillary permeability do not 

 involve the better known cyanide-sensitive oxidations, 

 but involve rather the 2 to 50 per cent (71, 224) of 

 tissue oxygen consumption which cyanide does not 

 inhibit even in high concentration. It is possible, too, 

 that the edema of prolonged ischemia arises from the 

 effects of anaerobically produced metabolic products 

 or from other substances liberated by hypoxic tissue 

 cells. In summary, the effects on capillary permeability 

 of arrested blood flow, and more specifically of 

 hypoxia, are still uncertain and require more carelul 

 studies both as to quantitative aspects and as to 

 mechanism. 



ADRENAL CORTICAL HORMONES AND FILTRATION 



coefficients. Adrenal hormones have frequently 

 been considered to be a factor in maintaining filtra- 

 tion coefficients and capillary permeability within 

 normal limits even after injury. Menkin (245) and 

 others (110, 332) observed that adrenal extracts and 

 some adrenal steroids inhibited or delayed the ap- 

 pearance of intravenously administered trypan blue 

 in the skin of rabbits where leukotaxine (110, 245) 

 or peptone (332) had been injected locally. Some 

 blanching of the skin was observed in the area treated 

 with adrenal cortical hormones (1 10, 332), suggesting 

 possible vasoconstriction. Hyman & Chambers 

 (163) found in the perfused hind legs of frogs that 

 the rate of edema formation was reduced by addition 

 of certain adrenal cortical extracts to the perfusing 

 fluid, but their method, like the preceding ones, did 

 not exclude possible changes in capillary blood pres- 

 sure. 



Renkin & Zaun (302) applied to this problem the 

 isogravimetric perfusion method of Pappenheimer & 

 Soto-Rivera (282) which permitted measurement of 

 a) filtration coefficients to indicate permeability to 

 fluid and protein, b) osmotic transients to indicate 

 permeability to small molecules, and c) blood flow 

 to identify vasoconstriction. Addition of adrenal 

 cortical extracts to both normal and adrenalectomized 

 preparations produced vasoconstriction which was 

 shown to be clue to the presence of small amounts of 

 an easily oxidizable substance, presumably epi- 

 nephrine. Limbs from adrenalectomized animals 



showed no increase of capillary permeability to 

 protein and filtration coefficients for fluid did not 

 differ significantly from normal. Addition of adrenal 

 cortical extracts to the perfusing fluid produced 

 slight decreases of the filtration coefficient, but evi- 

 dence of vasoconstriction was also present. The ad- 

 dition of epinephrine to the perfusing fluid in amounts 

 similar to that contaminating the extract produced 

 corresponding changes, both of resistance to flow and 

 of filtration coefficient. Permeability of the capillary 

 wall to sucrose was also normal in adrenalectomized 

 rats and was not affected by aqueous adrenal cortical 

 extract. 



The lack of agreement concerning the effects of 

 adrenal extracts and steroids emphasizes again (208) 

 the necessity for devising methods which separate 

 a direct action of substances on capillary permeability 

 per se from the indirect effects of complicating 

 vasodilatation or vasoconstriction. Vasodilatation 

 can increase capillary blood pressure; thus favoring 

 greater filtration through an unchanged capillary 

 wall. Conversely, vasoconstriction can reduce capil- 

 lary blood flow and pressure, and also the area of 

 capillary wall available for diffusion and filtration. 

 Such hemodynamic changes will, of themselves, 

 modify exchanges of substances, and thus simulate a 

 change of permeability. The quantitative measure- 

 ment of increases or decreases of capillary per- 

 meability is still one of the most difficult problems in 

 physiology. 



POROSITY OF THE INJURED CAPILLARY WALL. The 



effect of injury on the size of possible pores in the 

 capillary wall was considered by Krogh (184) in 

 1922. From the passage of soluble starch and the 

 retention of carbon particles he concluded that 

 pore diameter was not less than 50 A nor more than 

 2000 A. For normal limb capillaries of cats the 

 present corrected estimate for mean effective pore 

 diameter lies between 80 and 90 A (see sections 8 to 

 10). If it be assumed a) that injury merely enlarges 

 existing pores, and b) that Poiseuille's equation holds 

 for filtration through these pores, then a sevenfold 

 increase of filtration coefficient can be explained by a 

 65 per cent increase of pore diameter, i.e., from the 

 normal 80 to 90 A up to between 130 and 150 A. 

 Judging from the effects of reduced pH shown in 

 table 6.4 a doubling of filtration coefficient does not 

 increase protein passage measurably, whereas a 

 threefold to fourfold increase does. It may be, how- 

 ever, that injury increases the size or number of the 

 larger openings postulated by Grotte (126) and by 



