EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



995 



injury. A few quantitative measurements in terms of 

 filtration coefficients are available and provide esti- 

 mates of the increased porousness even though in- 

 formation on the "molecular alterations" of the 

 vessel walls is still completely lacking. 



In considering the mechanism of simple, chemical 

 injury, Krogh & Harrop (187) in 1921 described 

 'capillary stasis" as direct microscopic evidence of 

 increased permeability of the capillary wall. The steps 

 by which chemical injury leads to capillary stasis 

 merit full description, because capillary pressure, 

 flow, filtration, absorption, and diffusion are all 

 affected. The changes observed in a single, damaged 

 capillary form a unit lesion which helps to explain 

 the effects of more generalized injury. 



Blood corpuscles, when first entering a capillary, 

 are clearly separated by plasma. As long as the capil- 

 lary wall is normal this remains the case and flow con- 

 tinues. Even when capillary blood pressure is high, 

 filtration reduces the volume of plasma in flowing 

 capillary blood very slightly, because the fraction of 

 plasma filtered is normally less than 4 per cent of the 

 plasma volume at most, and usually 1 to 2 per cent. 

 However, as soon as injury is produced, e.g., by ap- 

 plying 25 per cent urethan or 10 per cent alcohol in 

 Ringer's solution, the corpuscles clearly begin to 

 move closer together as they flow along the capillary, 

 because plasma is lost progressively through the now 

 injured capillary wall. Eventually, at the venous end 

 of the capillary, nearly all the plasma having been 

 filtered off, the corpuscles become so closely packed, 

 and collectively so viscous, that they come to a stand- 

 still in the capillary and form a localized plug of cells 

 just short of the venule. Meanwhile plasma, with few 

 or many erythrocytes, continues to enter the arteriolar 

 end of the capillary, though much more slowly than 

 before and in a distinctly pulsatile fashion, because 

 entry is now limited by the volume of plasma being 

 filtered through the damaged capillary wall. 



The plasma of this blood is also lost by rapid filtra- 

 tion. The additional corpuscles are progressively con- 

 centrated in their turn and finally deposited cumu- 

 latively on the already existing column of erythrocytes 

 in the venous end of the capillary. Eventually a 

 column of packed cells fills the whole capillary and 

 takes on a characteristic, transparent, bright red 

 color, apparently because the erythrocytes are so 

 closely packed that light rays are no longer refracted 

 as they are when the surfaces of single corpuscles are 

 lormally separated by intervening plasma. Flow 

 ceases entirely in capillaries thus filled and plugged. 



If injury is severe, capillary stasis is irreversible. If 



injury is mild, resumption of flow is frequently ob- 

 served. The first indication of beginning recovery is 

 the loosening of corpuscles in the packed column, 

 followed by slow, then more rapid, squeezing of the 

 column into the stream of the nearest venous capillary 

 or venule. Here the cells can be seen separating 

 easily in the plasma of the venules as they are carried 

 away. In this respect simple stasis differs from the 

 "sludged" corpuscles described by Knisely et al. 

 (176) for more drastic states in which the corpuscles 

 adhere to each other and form minute emboli. 



Even after flow has returned some erythrocytes 

 and leukocytes usually remain adherent to the inner 

 surface of the damaged wall, but eventually these, 

 too, float free (199). Platelets may be seen adhering 

 to the wall for still longer periods and probably help 

 restore relative impermeability to protein as sug- 

 gested by Danielli's perfusion studies (61) in which 

 platelets reduced the rate of edema formation to 

 one-tenth that found with platelet-free perfusion 

 media. Platelet protein, in association with calcium, 

 has also been found to restore normal permeability 



(380- 



Chemical injury of the grade just described in- 

 creases capillary permeability enough to permit 

 passage of plasma proteins (200), colloidal dyes (107, 

 152, 184, 199), and colloidal starch (184) but, as 

 observed by light microscope, the walls of true capil- 

 laries still retain most of the carbon particles of in- 

 jected India ink (152, 184, 199). This is true also of 

 localized mechanical injury produced by compressing 

 capillaries with a glass rod (199), or by prodding 

 with a minute needle (37). In these simpler forms of 

 injury gross ruptures of the capillary wall are not 

 present because carbon particles, as well as erythro- 

 cytes, are retained as plasma is filtered off. 



FILTRATION COEFFICIENTS, k c , OF INJURED CAPILLARIES. 



The permeability of injured capillaries has been 

 measured in the frog's mesentery by determining their 

 filtration coefficient during stasis using the method 

 already described for normal capillaries (200). 

 Figure 6.6 shows filtration rates plotted against 

 capillary blood pressure, injury having been pro- 

 duced by irrigating the mesentery with 10 per cent 

 alcohol or 1'. 10,000 mercuric chloride in Ringer's 

 fluid. As with the normal capillary wall, filtration 

 increased linearly with capillary blood pressure. 

 Comparison of the regression lines for injured capil- 

 laries (above) and normal capillaries (below) indi- 

 cates, however, that the filtration coefficient was 



