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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



local changes of pressure from contraction of fibrin 

 strands or of newly formed connective tissue. It may 

 be, too, as Guyton suggests, that the negative pres- 

 sures result in part from intermittent evacuation of 

 lvmphatics by the mechanical pumping which ac- 

 companies movement. 



Again, the kidney has proved to be a special case. 

 Gottschalk (123) found interstitial fluid pressures 

 averaging +10 mm Hg in rats, guinea pigs, rabbits, 

 and cats, and +16 mm Hg in dogs. These pressures 

 rose promptly whenever renal venous pressure or 

 ureteral pressure was increased. Inside the renal 

 capsule the pressures in tubules, peritubular capil- 

 laries, and the interstitium changed together, and by 

 approximately equal increments, without evidence of 

 the breaking pressure found by McMaster (237) in 

 skin and subcutaneous tissue. It seems clear that inter- 

 stitial fluid pressure, like capillary blood pressure, 

 must be considered tissue by tissue. 



5. PROTEINS IN EXTRACAPILLARY FLUIDS; U,f 



A. Capillary Filtrate From Limb 

 Capillaries; Protein Content 



The concentration of protein in the fluid which is 

 filtered through the capillary wall is an important 

 figure for several reasons. In the first place, it is the 

 most direct measure of capillary permeability to 

 protein, and hence of the effectiveness of the capillary 

 wall as a protein-retaining membrane. Second, this 

 original capillary filtrate is the raw material from 

 which interstitial fluid, and eventually lymph, are 

 produced. Third, just as filtration is produced by 

 P c — P, f , so absorption is produced by U P i — 11,/, 

 i.e., by the effective osmotic pressure of the plasma 

 proteins. Fourth, studies on the volumes and protein 

 concentrations of capillary filtrates in various tissues, 

 and under various conditions, have established the 

 existence and approximate magnitude of a physio- 

 logically important circulation of protein from capil- 

 lary blood, through the interstitial fluid compart- 

 ment around the tissue cells, thence to the lymphatics, 

 lymph nodes and via the lymphatic trunks back to 

 the circulatory system. 



By 1 898 large regional differences in the concentra- 

 tion of protein in lymph were well known, and corre- 

 sponding differences in the permeability of capillary 

 walls to protein were postulated. Thus Starling wrote: 

 "The lymph in the limbs, the filtrate through the im- 

 permeable limb capillaries, contains only from 2 to 3 

 per cent proteids; that from the intestines contains 



from 4 to 6 per cent proteids; while that from the 

 permeable capillaries of the liver contains from 6 to 8 

 per cent proteids — in fact almost as much as the 

 blood plasma itself" (346). Over half a century of 

 work on lymph has confirmed these figures, providing 

 some allowance is made for improved analytic meth- 

 ods. In the most recent compilations (79, 386) the 

 total protein in lymph from legs at rest ranged from 

 1.3 to 3.3 g per 100 ml; from intestine, 2.8 to 4.0, and 

 from liver, 4.4 to 6.1. However, the interpretation of 

 these figures, particularly with respect to the lymph 

 from the limbs, has changed. Starling (346) and also 

 Drinker & Yoffey (79) believed that the protein con- 

 tent of lymph and of interstitial fluid must be identi- 

 cal, a view that now is not tenable. Hence it is helpful 

 to consider in sequence a) the protein content of the 

 original capillary filtrate, b) the fate of this protein as 

 the capillaries absorb fluid, c) the resulting protein 

 content of interstitial fluid, and, finally, d) the protein 

 content of lymph. For reasons already described in the 

 previous section it has so far proved impossible to 

 collect normal capillary filtrate directly. However, 

 for limb capillaries relatively consistent estimates of 

 the protein content of capillary filtrate have been ob- 

 tained indirectly a) from analyses of certain edema 

 fluids, b) from studies of plasma proteins during 

 venous congestion, and c) from studies of lymph 

 during venous congestion and during chronic plasma- 

 pheresis. 



In severe hypoproteinemic edemas, e.g., nephrosis, 

 malnutrition, and amyloid disease, absorption is pre- 

 sumably abolished because of the lowered osmotic 

 pressure of the plasma proteins. Hence, as previously 

 reviewed (207), the presence in these edema fluids of 

 0.09 to 0.40 per cent of protein, with most values 

 between 0.1 and 0.27 per cent, provided the first 

 estimates of the protein content of capillary filtrate 

 with the reservation, however, that disease may have 

 modified the permeability of the capillary walls. In 

 cardiac failure, edema fluids contained from o. 1 to 

 1 .0 per cent protein with an average of 0.4 per cent. 



In normal subjects, elevating venous pressure to 

 25 mm Hg or more, i.e., to exceed the osmotic pres- 

 sure of the plasma proteins, also abolishes absorption 

 of fluid. Landis et al. (211) congested the forearms of 

 human subjects and computed from the hematocrit 

 ratios of venous blood the volume of filtrate from 

 each 100 ml blood plasma, and divided this into the 

 amount of protein simultaneously lost from the 

 plasma during the same congestion. The errors 

 involved in small filtered volumes, and even in tripli- 

 cate protein analyses, prevented any conclusions with 

 congestions of 40 mm Hg; but at 60 mm Hg the calcu- 



