THE QUANTITATIVE DETERMINATION OF IRON KINETICS AND HEMOGLOBIN SYNTHESIS IN HUMAN SUBJECTS*

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Abstract
A mathematical model of iron kinetics is proposed and used in the study of 13 normal subjects and 6 patients with endogenous hemochromatosis. Of central importance to this model is the concept of a labile erythropoietic iron pool interposed between iron bound to transferrin in plasma and iron irreversibly fixed in erythrons for heme synthesis. This model is applied to measurements of radioirin in plasma, circulating red cells, and surface counting rates over liver, spleen, and marrow. Together with measurements of plasma iron concentration and red cell volume, this permits calculation of hemoglobin synthesis, mean erythron life span, mean effective erythron hemoglobinization time, storage iron deposition, and miscible storage iron. Results are presented that are in agreement with established concepts concerning the life span of normal erythrocytes, erythron maturation, and body iron stores. Increased storage iron deposition, miscible storage iron, and plasma iron removal were evident in all hemochromatotic patients. Hemoglobin synthesis and erythron life span were normal in five patients with he-mochromatosis; one was found to have compensated hemolysis. Erythron hemolysis, whether in marrow, or subsequent to erythron entry into the circulation, may be detected and quantitated by analysis of plasma radio-iron, which, as a result of hemolysis, equilibrates at a constant value in 10 days or less. Evidence is presented suggesting that there is in-significant erythron iron bypass of plasma, either by destruction of maturing erythrons in the marrow or via erythrophagocytosis in marrow of circulating erythrocytes.