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HANDBOOK. OF PHYSIOLOGY 



CIRCULATION II 



creases considerably. Moreover, Brown et al. (24) 

 found that even at normal venous pressures cooling 

 the surface of the forearm to 4 C produced a slow but 

 steady increase of the reduced forearm volume pre- 

 sumably because of filtration and augmented inter- 

 stitial fluid volume. These results suggested "cold 

 injury" of surface capillaries and diminished effective 

 osmotic pressure of the plasma proteins. Passage of 

 protein through the capillary wall in severe cold has 

 been described by Lewis (218), who found up to 3 g 

 per cent of protein in the edema fluid. In summary, it 

 appears that for intact tissues the effects of moderate 

 changes of temperature on filtration coefficients can 

 be explained fairly well by the changing viscosity of 

 capillary filtrate. At very high and very low tem- 

 peratures other factors, as yet unanalyzed, become 

 more important. 



C. Adsorbed Plasma Protein and Filtration Coefficients 



The functional dimensions of capillary pores, and 

 hence the filtration coefficients of capillaries, are 

 probably determined in part, by a layer of adsorbed 

 plasma protein. Krogh & Harrop (186) were the 

 first to note that perfusion of extremities with non- 

 protein colloids fails to prevent edema. Their observa- 

 tions were confirmed and extended by Drinker (74), 

 Danielli (61), and Shleser & Freed (332). Kinter & 

 Pappenheimer (cf table 6.3) found that dextrans 

 failed to exert their full osmotic pressure in vivo 

 unless more than 0.2 per cent protein was present 

 in the perfusion fluid. Net filtration usually occurred 

 in dextran-Ringer perfused muscle at all venous 

 pressures; 10 to 20 min after addition of 1 per cent 

 plasma protein the direction of net fluid movement 

 was reversed as the osmotic pressure of the dextran 

 became effective across the capillary walls. The 

 phenomenon was fully reversible and could be re- 

 peated several times on the same preparation during 

 the course of a few hours. The capillary filtration 

 coefficient was usually more than doubled when 

 Ringer's solution (295) or Ringer-dextran solutions 

 were substituted for plasma. In nine experiments the 

 filtration coefficient averaged 0.016 ± .003 ml per 

 min per 100 g tissue during perfusion with blood, 

 0.037 ± .002 during perfusion with protein-free red 

 cell suspensions, and 0.019 ^ °°3 when protein was 

 restored to the perfusion fluid. The effect appears to 

 be nonspecific, since normal filtration coefficients 

 were found in cat or rat hind limbs perfused with 

 human or bovine serum albumin (295), cat hemo- 

 globin, or bovine hemoglobin (299). 



table 6.3. Effective Osmotic Pressures of Clinical 

 Dextran in Capillaries of Perfused Cat Hind Limbs 



From unpublished experiments of Kinter and Pappen- 

 heimer. 



The minor axis of serum albumin is about 30 A 

 and complete removal of albumin from the inside of 

 a pore might increase effective pore radius by this 

 amount. Given a mean pore radius of 45 A (see 

 sections 9 and 10), the filtration coefficient would be 

 expected to increase by the factor (30 + 45) 4 -f- (45) 4 

 or more than sevenfold. A reversible increase of this 

 magnitude was observed in only one preparation, 

 but it is possible that even prolonged washout with 

 protein-free solutions fails to remove all adsorbed 

 protein. The effects of adsorbed protein should be con- 

 sidered, however, in comparing pore dimensions 

 calculated from permeability measurements with pore 

 dimensions observed in electron micrographs. 



D. Effects of Injury on Filtration, Absorption, 

 and Filtration Coefficients 



capillary stasis. Cohnheim in 1867 postulated a 

 "molecular alteration in the vessel walls" and aug- 

 mented "porousness" to explain the transudation of 

 fluid, protein, and cells in inflammation (42, 43). 

 Since then abundant qualitative evidence has indi- 

 cated that injury of many types increases the perme- 

 ability of the capillary wall to fluid and protein (207). 

 Inflammation is, however, an exceedingly complex 

 series of reactions (246, 247, 344), of which increased 

 capillary permeability is only one part. Physiologists 

 have, therefore, tended to study simpler forms of 



