EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



9 8l 



sures and rapid initial filtration found in the lower 

 extremities during sitting or quiet standing. How- 

 ever, the occurrence of edema indicates, of itself, 

 that the tissue elements are slowly separable, and 

 so cannot resist higher than normal interstitial fluid 

 pressures indefinitely. P,, in manifest edema of man 

 has proved to be highly variable though frequently 

 above normal limits. During accumulation of edema 

 fluid it ranged from 4 to 18 cm water in one series 

 (336) and from 4 to 26 cm water in others (30, 340), 

 returning in all instances toward normal or below as 

 the edema fluid disappeared. Holland & Meyer (158) 

 reported pressures below normal in edema, but their 

 method was open to question (238). In the skin of the 

 mouse McMaster (238) found that P,, was little 

 elevated in some forms of experimental edema and 

 greatly elevated in others with the further anomaly 

 that in some instances beefy indurations occurred in 

 which paucity of freely movable fluid permitted only 

 measurement of interstitial resistance to slow intro- 

 duction of fluid. In general, both clinically and experi- 

 mentally, the highest interstitial fluid pressures were 

 found in skin which had become recently and rapidly 

 edematous. Slowly developing edema often occurred 

 without significant elevations of P,/. The distensibility 

 of tissues is also an important variable. The eyelids 

 accommodated rapidly injected fluid most easily, 

 the face and pretibial areas least easily (28). In 

 edema P,j was found to be lower, 1 to 8 cm water in 

 the former and higher, 2 to 1 4 cm water, in the latter. 



The limited and transitory resistance of tissues to 

 slowly introduced fluid has been described quantita- 

 tively by McMaster (237). At pressures ranging from 

 4.5 to 14 cm water the entry of Locke-Ringer's 

 solution through a needle into a tissue was slow and 

 also intermittent. Above these pressures, which he 

 termed the "breaking point," fluid flowed into the 

 tissue continuously and at much higher rates, which 

 increased linearly with further pressure increments. 

 Once the tissues had been separated by this "breaking 

 pressure," high rates of flow were observed even at 

 low pressures (237). The resistance which the normal 

 interstitium offers to flow of filtered fluid from 

 capillaries to lymphatics has been demonstrated in 

 different fashion recently during venous congestion in 

 the dog's leg by Irisawa & Rushmer (166). When 

 venous pressure was elevated to between 65 and 

 55 cm water for 270 min the pressure in the draining 

 lymphatic vessels rose very slow-ly reaching, after 90 

 min, plateaus of 18 cm water or less. 



The positive interstitial fluid pressures so far de- 

 scribed were obtained in acute experiments of rela- 



tively brief duration. There is some evidence, how- 

 ever, that interstitial fluid pressure may be slightly 

 but definitely negative under some conditions and in 

 more prolonged observations. McMaster (235, 236) 

 observed at atmospheric pressures that fluid flowed 

 intermittently from a needle into cutaneous tissue at 

 rates up to .08 mm 3 per min. This suggests a negative 

 interstitial pressure, but the subatmospheric pressure 

 required to arrest inflow was not determined. Inflow 

 of fluid was increased in transitory fashion by painful 

 stimuli and by the intravenous injection of hypertonic 

 sucrose solution. These changes are explicable on the 

 basis of increased absorption by capillaries during 

 vasoconstriction and decreased capillary blood pres- 

 sure in the first instance, and by temporary hyper- 

 tonicity of capillary blood in the second instance. 

 Outflow of fluid, that could be arrested by positive 

 pressure on the fluid in the needle, was found during 

 venous congestion and when an irritant solution pro- 

 duced localized edema. These outflows may be 

 explained respectively by heightened capillary pres- 

 sure and by injury. On the other hand, the hyper- 

 emia induced by heat, either directly or reflexly, 

 increased inflow of fluid into the tissue, despite ob- 

 served vasodilatation and presumable elevation of 

 capillary pressure. It is possible that locally increased 

 arterial pulsation may, by pumping action, have 

 evacuated the regional lymphatics and so increased 

 inflow mechanically (283, 373). 



Very recently Guyton el al. ( 130) have extended the 

 time of observation to hours or days. Immediately 

 after insertion of needles, and in agreement with 

 previous studies, slightly positive readings, e.g., + 1 

 to +2 cm water, were obtained. During the next 4 or 

 5 hours, however, the balancing, null-point pressures 

 decreased gradually to —2 or —3 cm water with in- 

 dications that this decline was still continuing. To ex- 

 tend readings to days or weeks, perforated plastic cap- 

 sules were implanted in the subcutaneous tissue and 

 after 1 or 2 weeks pressures were —3 to — 14 cm water 

 in the abdominal wall, axillary space, scrotum, muscle, 

 and quiet limb. They decreased slowly, over a period 

 of minutes, when the respective parts of the body were 

 moved. Venous congestion changed the pressure to 

 positive values, but not until edema was apparent. 

 Protein in the capsule also produced positive values. 



Chronic experiments of this type tend to avoid some 

 of the artifacts, e.g., acute reactions to the insertion of 

 a needle or pipette, that may influence immediate 

 measurements of interstitial fluid pressures. On the 

 other hand, their long duration introduces the possi- 

 bility of slower reactions to foreign bodies, including 



