Brilliant vital red injected into the blood stream of dogs is slowly taken up by phagocytes in various parts of the body, but eventually an equilibrium is established, after which the concentration as measured in the plasma remains almost constant for long intervals of time.
This equilibrium can be disturbed by injecting more dye, and in this case the phagocytes resume ingestive activity, apparently with normal or nearly normal vigor. This activity continued until a rather large part of the newly injected dye has been removed, and as the reaction again slows up we note that both plasma and tissues contain more dye than before. It is difficult to be certain that the distribution ratio of dye between plasma and tissues remains unaltered with dosage, but evidence indicates that for non toxic doses, at least, this is approximately true.
This study of this partition ratio is complicated by the fact that the liver slowly excretes dye into the bile, and this helps to reduce the amount of dye in the body. Partial correction for this factor can be made by ascertaining the dye output in bile fistula dogs. These latter studies show that dye elimination into bile is relatively less efficient when large doses of dye are given to the animal than with smaller dosage. This undue retention of dye in the body with large dosage helps to maintain the dye concentration in the plasma at unduly high levels. These peculiarities in liver excretion have an important bearing on liver physiology in general, and in addition they also have an important application in connection with the theory of "blockade of the reticulo-endothelial system." It is now obvious that prolonged retention of dye in the blood stream does not of itself prove that this group of phagocytic cells is "blocked" against the entrance of foreign material. Altered excretion by liver, kidney, etc. must be ruled out before we can accept such data as evidence of "blockade."