420 ANNUAL REPORT SMITHSONIAN INSTITUTION, 194 5 



erally it is the albumins and the y-globulins that appear to be lost 

 more readily than either other globulins of larger net charge or 

 fibrinogen. The significance of this observation is twofold. On the 

 one hand, it reflects the conditions that obtain when proteins leave 

 the blood stream, on the other the replacements that must be made if 

 normal composition of the blood is to be restored by therapy. 



Although the smallest plasma proteins of largest net charge, the 

 albumins, and the largest globulins of smallest net charge, the 

 y-globulins, leave the blood stream most readily, it is the albumins 

 which have the largest effect in controlling the equilibrium in water 

 and electrolytes between blood and the tissues. The y-globulins rep- 

 resent but 11 percent of the plasma proteins, the albumins five or more 

 times that much. The molecular weight of the y-globulins is two or 

 more times that of the albumins. On the basis of mass alone, there- 

 fore, the y-globulins — which as we shall see are the bearers of the 

 immune properties of the blood — contribute less than one-tenth as 

 much as the albumins to maintaining the volume of the blood. This 

 calculation neglects the greater contribution of the albumins which 

 depends upon their greater net charge. Indeed, albumins are respon- 

 sible for nearly 80 percent of the osmotic activity of the blood. 

 Accordingly it is the albumins in plasma which are in large part 

 responsible for the therapeutic value of plasma in the treatment of 

 shock. 



The fact that fibrinogen leaves the blood more slowly than albumin 

 may be associated with its greater length. On the whole, molecules 

 of the same diameter should pass an inert membrane inversely as their 

 length. The presence of fibrinogen in the blood in small amount 

 must be associated with its special functions, which we shall examine 

 later in connection with the clotting of the blood. Its osmotic con- 

 tribution is negligible but its contribution to viscosity is enormous and 

 this effect might be deleterious were fibrinogen present in large amount. 

 Under these circumstances, it brings about clumping of the red cells 

 as do many other highly asymmetric molecules. 



If substances other than the plasma proteins are injected into the 

 blood, their fate also appears to depend upon their dimensions. Saline, 

 glucose, and most substances that have thus far been suggested as 

 blood substitutes have diameters less than 20 angstrom units and, 

 unless they are very asymmetrical, leave the blood stream rapidly. 

 They thus exert temporary, but do not have sustained, influence in 

 maintaining blood volume. 



Asymmetric molecules appear to leave the blood stream more slowly 

 and may even accumulate in the blood stream as evidenced by their 

 influence on the clumping and sedimenting of red cells. Such mole- 



