Rex L. Huff

PLASMA AND RED CELL IRON TURNOVER IN NORMAL SUBJECTS AND IN PATIENTS HAVING VARIOUS HEMATOPOIETIC DISORDERS

One of the obvious uses which may be made of a tracer in biological studies is the determination of rates. Zilversmitt and associates (1) and more recently London (2) have called attention to this use of a tracer. Only when the isotope can be added without effectively changing the amount or concentration of material in a steady state system can such an application be made. Not until recently has radio iron been available which had sufficiently high specific activity to tag plasma iron without changing its concentration. The amount of iron leaving and entering the plasma would be significant in determining an abnormal turnover rate in some other system of the body containing iron, for example, the red cells. The present theory of iron metabolism conceives of plasma as a pool into which iron is returned before being resynthesized into the complex organic substances, hemoglobin, myoglobin, cytochromes, peroxidases, and ferritin which are so important to body function. Since the approximate normal rate of turnover of red cell iron is known, and since the major portion of this element in the body resides in the red cells, it would be expected that abnormalities in this rate would be directly reflected in plasma iron turnover rates. This paper concerns the plasma iron and red cell iron turnover data on 75 human subjects who were given amounts of iron which did not alter the steady state systems. It is shown that such turnover rates do, indeed, agree with the clinical and laboratory data concerning normal red cell life, abnormal rates of destruction and abnormal rates of formation of red cells. It is believed that the data ascertained from the type of study described here are of value

Depression of Tracer Ion Uptake Curve in Rat Erythrocytes Following Total Body X-Irradiation

Summary 1. A method of demonstrating the depression of the erythroid portion of the bone marrow by x-irradiation with the use of Fe59 is presented. 2. Graphs of the red cell FeS9 uptake curve in rats at various dosage levels of total body x-irradiation and at varying times after irradiation are given.

The Blood Volume of the Adult Rat, as Determined by Fe59 and P32 Labelled Red Cells.∗

Conclusions 1. The blood volume of normal rats determined by the use of Fe59 labeled red blood cells is essentially the same as with P32 labeled cells. 2. The use of P32 labelled red blood cells is hence satisfactory for the determination of blood volume. 3. Determinations with P32 indicate that the blood volume of the normal rat is 4.59 ± 0.57/cc 100 g body weight; the total red cell volume 2.16 ± 0.20 cc/100 g body weight; and the hematocrit 45.8 ± 2.6.

Increase in circulating red cell volume of normal and hypophysectomized rats after treatment with ACTH.

Conclusions 1. Administration of ACTH prevents the decrease in the total circulating red cell volume which is normally found in hypophysectomized rats. 2. Administration of ACTH for 116 days to normal rats elevates the total circulating red cell volume to approximately 1.3 times that of the normal untreated controls.

Use of a chelating agent for accelerating excretion of radio-iron.

Summary 1. Excretion of parenterally administered radio-iron is approximately 5 to 10 times as great in feces as in urine. The rate of excretion varies with the location of the tracer within the various iron pools in the body, (for example, cells, liver, reticulo-endo-thelial system, etc.). This is illustrated by high plasma levels of radio-iron, associated with high excretory rates in feces and urine. Fifty-five days after injection of tracer iron there is a second maximum in excretory rate which can be shown to correspond with a loss of radio-iron from the largest pool, the circulating erythrocytes. When “Fe-3 Specific” is administered intraperitoneally to animals which have been given iron 59, there is a prompt and marked increase in both the urinary and fecal excretory rates by a factor of 2 to 2.5. 2. The addition of “Fe-3 Specific” to the diet of rats causes an increase in the fecal and urinary excretion of intravenously administered radio-iron by approximately a factor of 2. 3. When labelled iron and “Fe-3 Specific” are fed simultaneously, a marked increase in urinary excretion of the tracer occurs. However, the amount found in feces is nearly the same as in controls. Thus the decrease in net retention resulted primarily because of increased urinary excretion. 4. Feeding as much as 9.6 g of “Fe-3 Specific” to animals at a rate of 400 mg per day, was not associated with any change in hematocrit nor any grossly observable abnormality in the animals.

Epilation in the Non-Irradiated Member of Parabiotically United Rats.∗

Discussion and Conclusion Parabiotically united rats influence their partners by the mixing of their body fluids through their common circulation. Therefore, an effect such as epilation must result from the transfer of material from one member to the other. Whether the epilation represents the passage of physiologically active material from the radiated to the non-radiated or is a manifestation of loss of material from the non-irradiated to the irradiated is not demonstrated.

Depression red cell iron turnover by transfusion.

Summary (1) A profound decrease in the red cell iron turnover occurred after experimental increase in the red cell volume of rats. (2) A major portion of the tracer was found in the liver at necropsy.