STUDIES IN IRON TRANSPORTATION AND METABOLISM. II. THE MECHANISM OF IRON TRANSPORTATION: ITS SIGNIFICANCE IN IRON UTILIZATION IN ANEMIC STATES OF VARIED ETIOLOGY 1

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Abstract
The changes in the plasma and "easily split-off" forms of blood Fe as influenced by conditions of absorption and utilization were studied in man. Plasma or serum Fe in Fe deficiency states was uniformly low. With decreased red cell formation (e.g., hypoplastic anemia and pernicious anemia in relapse), it tended to be high. When bone marrow was unusually active in erythrocytogenesis (e.g., following acute hemorrhage and liver induced remission in pernicious anemia), the plasma Fe conc. was low. In the hemolytic states, the plasma Fe was in equilibrium between the amts. of Fe being added to the blood stream us a result of the hemolytic process, and the amt. being withdrawn by the hyperplastic bone marrow. When the equilibrium was disturbed by splenectomy in congenital hemolytic icterus, the plasma Fe fell to a level consistent with the rate of rapid hemoglobin synthesis. During the most active period of a phenylhydrazine hemolysis, the plasma Fe increased. Following the administration of single large doses of Fe salts by mouth, the conc. of Fe in plasma was increased frequently to from 3 to 10 times its basal level. "Easily split-off" blood Fe proved to be relatively stable. In the Fe deficiency states, it was either normal or lower than normal. With depressed hemoglobin synthesis and diminished erythrocytogenesis, it was as likely to be low-normal as it was to be high-normal. No significant changes occurred in pernicious anemia after liver therapy. "Easily split-off" blood Fe was not influenced by increased rates of red cell destruction, and did not increase following the administration of single oral doses of Fe salts. Iron therapy in patients with Fe deficiency and slightly low "easily split-off" Fe values was attended by an increase in the fraction to normal levels; but this increase was relatively independent of the changes in plasma Fe and erythroid elements. An exchange of Fe from the "easily split-off" to the plasma Fe fraction was not observed after incubation of unclotted blood at 37.5[degree] for 6 to 8 hr. periods. Iron was evidently transported as plasma Fe, and the physiologic function of "easily split-off" blood Fe remained to be defined.