978 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



.120 



RATE OF 

 FILTRATION 

 ML /MIN / 100 ML 

 FOREARM 

 TISSUE -080 



.040- 



0^ 



JS PRESSURE = /T\ 



CM WATER FROM ^-^ 



VENOU 

 60 



TIME ZERO 



30 



-20 



INCREASE 



OF 



INTERSTITIAL 



FLUIO 



PRESSURE 



ABOVE 



RESTING 



LEVEL 



CM H 2 



(CALC.) 



10 



20 40 



TIME - MIN 



2 4 6 



VOLUME OF NEWLY FILTERED 



INTERSTITIAL FLUIO 



ML/IOOML OF FOREARM TISSUE 



fig. 4.1. Chart showing decreasing filtration rate ( in A) measured in human forearm by 



pressure plethysmograph when venous pressure was elevated to 60 cm H>0 for 80 min. Interstitial 



fluid pressure (O O) was calculated by dividing the cumulative decrease of observed filtration 



rates by the previously determined average normal filtration coefficient (.0033 ml/ 100 ml forearm 

 tissue/min/cm H2O increase of venous pressure), and then correcting each value for the local in- 

 crease of plasma protein concentration and of n,,( produced by net filtration. As shown in A calcu- 

 lated interstitial fluid pressure increases steadily with time, reaching a maximum of almost 30 cm 

 H 2 by 75 min. In B the same calculated interstitial fluid pressures are charted against the cumula- 

 tive volume of added interstitial fluid. As the interstitial compartment is distended by an increasing 

 volume of filtered fluid, interstitial pressure in the forearm tissues probably rises slowly at first and 

 then more rapidly. [Recalculated from data of Landis & Gibbon (209).] 



of forearm tissue. As shown in figure 4.1 {left) when 

 venous pressure was raised to 60 cm water, the initial 

 filtration rate was .156 ml per min per 100 ml of 

 forearm tissue but declined rapidly to less than .040 

 after 75 min of congestion. At this time the volume of 

 newly filtered fluid was approximately 6 ml per 100 

 ml of tissue, i.e., about 60 per cent of the amount 

 which produces manifest edema, detectable by 

 "pitting on pressure." Knowing the decrease of filtra- 

 tion rate, the normal filtration coefficient (209), and, 

 approximately, the increase in the osmotic pressure 

 of the plasma proteins of the blood in the congested 

 forearm (188, 211), it is possible to calculate inter- 

 stitial fluid pressure, with results shown in figure 4. 1 . 

 Accumulations of interstitial fluid from prior filtra- 

 tion also increased the rate at which extravascular 

 fluid was removed from the forearm (188, 209), as 

 would be expected with higher interstitial fluid pres- 

 sures. It is still impossible to decide to what extent this 

 fluid was removed via the blood capillaries by absorp- 

 tion or via lymphatics by flow, though indirect evi- 

 dence (188) indicated that small accumulations were 

 probably removed by the former, larger accumula- 

 tions by the latter in addition. The importance of 



interstitial fluid pressure seemed clear, although de- 

 pendable direct measurements were not available as 

 yet. 



In a review of this topic in 1934 (207) it was neces- 

 sary to consider the conflicting views then current 

 concerning bound and free water in the interstitial 

 fluid compartment. It is now generally agreed on the 

 basis of many studies by several dilution methods 

 that the volume of truly "bound water" is negligible. 

 Yet in normal tissues interstitial fluid cannot be 

 identified microscopically as a distinct and continuous 

 compartment or layer around capillaries or between 

 cells except in a few locations. This is not surprising 

 because a simple calculation shows that if the normal 

 volume of interstitial fluid, approximately 1 5 per 

 cent of gross tissue volume, is distributed uniformly 

 between surfaces of cells, connective tissue fibrils, 

 blood capillaries, etc., the average thickness of this 

 layer cannot be greater than 1 n and is probably less 

 than 0.5 fi. This coincides with the findings of Mc- 

 Master & Parsons (240, 241) who injected dye solu- 

 tions into small lymphatic vessels and observed under 

 high magnification that the dye penetrated into the 

 tissues in the form of hair-like projections or "bristles," 



