Ferrokinetics: a biologic model for plasma iron exchange in man

Cook, James D.; Marsaglia, George; Eschbach, Joseph W.; Funk, Donald D.; Finch, C. A.

doi:10.1172/jci106228

Cited by 141 publications

(66 citation statements)

References 16 publications

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“…Blood samples were obtained from the tail vein on the opposite side, and the rate of radioiron disappearance from circulation (t 1/2 ) was determined by least squares regression analysis. Based on the plasma iron (PI), Hct, and clearance half-time of 59 Fe (t 1/2 ), plasma iron turnover (PIT, mg/dL whole blood/day) was calculated from a standard formula given in Equation 1 [16]: (1) where 0.9 is the correction for trapped plasma in the hematocrit (0.98) and to convert venous hematocrit to whole body hematocrit (0.92). The extravascular flux, a function of plasma iron concentration [16], was subtracted to obtain tissue iron uptake (TIU), as given in Equation 2:…”

Section: Methodsmentioning

confidence: 99%

Serum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors

R'Zik

Béguin

2001

Experimental Hematology

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Objective. Serum levels of the soluble transferrin receptor (sTfR) vary depending on the erythropoietic activity and iron status. In vitro, sTfR shed in the incubation medium correlates well with cellular TfR, but this relationship has never been established in vivo. To determine the value of serum sTfR as a quantitative marker of the body mass of tissue TfR, we designed experiments to examine the correlation between serum sTfR and tissue TfR in rats with various degrees of erythropoietic activity or iron status. Materials and Methods. We studied changes in erythropoietic activity in normal rats as well as in animals experiencing hemolysis, phlebotomy-induced iron deficiency, transfusion-or thiamphenicol-induced erythroid aplasia, or inflammation. At the end of follow-up, ferrokinetic studies were performed and animals were sacrificed. Organs were isolated and homogenized to determine the total mass of tissue TfR from the sum of tissue solubilized TfR in the bone marrow, spleen, liver, and blood cells (direct method). An indirect method was developed to derive the corporeal mass of tissue TfR from a representative marrow sample. Results. As expected, serum sTfR and total mass of tissue TfR varied as a function of iron status and erythropoiesis. Relative erythroid expansion in the spleen was greater than in the bone marrow. With the exception of phlebotomized animals, the indirect method correlated very well with direct measurements of the total mass of tissue TfR ( r ϭ 0.97, p Ͻ 0.0001). There was a close relationship between the total mass of tissue TfR and the total mass of serum sTfR ( r ϭ 0.79, p Ͻ 0.0001). Serum sTfR represented approximately 5-6% of the total mass of tissue TfR in most experimental situations, but this ratio was twice as high during iron-restricted erythropoiesis. In addition, the ratio could be higher or lower in nonsteady-state situations, because changes in tissue TfR occurred faster than those of serum sTfR. Conclusions. Serum sTfR represents a constant proportion of the total mass of tissue TfR over a wide range of erythropoietic activity. However, iron deficiency results in a higher proportion of serum sTfR, and the pace of change in serum sTfR levels is slower than that of tissue TfR mass.

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Section: Methodsmentioning

confidence: 99%

Serum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors

R'Zik

Béguin

2001

Experimental Hematology

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“…After removal of a standard, the remainder was injected through the foreleg vein. Eight 1-mil plasma samples were obtained during the following, 2 h. The PIT, expressed as mg Fe/100 ml whole blood/day was calculated The erythron iron turnover (EIT) was then derived from the PIT (6) by subtracting the nonerythroid fraction as in the following formula :2 EIT = PIT -(Serum iron [,Mg/100 ml] X plasmatocrit X 0.0035) (2) Erythroid cells of the marrow were labeled by injecting intravenously over a 15-min period 1.5 mCi 5Fe citrate (sp act of 10-15 mCi/mg, molar ratio Fe/citrate < 1: 30). 18 h later when the radioiron was maximally localized in the erythroid precursors, a marrow biopsy was obtained from the posterior iliac crest with an electrical drill (Synthes AG., Waldenburg, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Marrow erythroid and neutrophil cellularity in the dog.

Deubeleiss¹,

Dancey²,

Harker³

et al. 1975

J. Clin. Invest.

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A B S T R A C T This paper describes a method for determining the number of marrow erythroid and neutrophil cells in which the cellularity of marrow sections was related to that of the total marrow by radioiron dilution. Tissue sections were prepared from methacrylateembedded dog marrow biopsies, and neutrophils were identified by staining of their primary granules. After correction of direct section counts for multiple counting error, accurate neutrophil-erythroid ratios were established with a coefficient of variation of less than 10% when 104 cells were examined. An average neutrophil-erythroid ratio of 1.2 was found in six normal dogs.The total number of nucleated red cells in the dog was 5.48±0.78 X 109/kg (+1 SD), and the corresponding erythron iron turnover was 0.90±0.11 mg Fe/100 ml whole blood/day. The total number of marrow neutrophils, derived from the neutrophil-erythroid ratio, was 6.6±0.59 X 109 cells/kg, of which 1.4 were promyelocytes and mvelocytes, 2.3 were metamyelocytes and bands, and 3.0 were segmented neutrophils. Leukopheresis studies were carried out in six dogs to confirm the accuracy of these cellular measurements. 1\Iarrow counts showed a mean decrease of 22.7 X 109 cells or 35% of the postmitotic neutrophil pool, and it was calculated that 10.2 x 109 additional cells had been taken from already circulating blood. This estimated deficit of 32.9 X 109 was almost identical to the 33 X

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“…Plasma iron turnover was calculated by the formula of Bothwell and Finch (4) from the mean serum iron measurements before and 2 hr after 'Fe injection. Erythron iron turnover was derived by subtracting the calculated nonerythron turnover from the plasma iron turnover (5). Plasma and erythron iron turnovers in milligrams per day were calculated from the product of the plasma or erythron iron turnover per 100 ml of whole blood (4,5) and the blood volume derived from the red cell volume.…”

Section: Measurements Of Erythropoiesismentioning

confidence: 99%

“…Erythron iron turnover was derived by subtracting the calculated nonerythron turnover from the plasma iron turnover (5). Plasma and erythron iron turnovers in milligrams per day were calculated from the product of the plasma or erythron iron turnover per 100 ml of whole blood (4,5) and the blood volume derived from the red cell volume. In normal subjects, the blood volume was calculated from the red cell volume using a body hematocrit to venous hematocrit ratio of 0.92; in nine polycythemic patients with moderate splenomegaly, a ratio of 0.98 was assumed; in three patients' with marked splenomegaly, a ratio of 1.04 was used (6).…”

Section: Measurements Of Erythropoiesismentioning

confidence: 99%

Erythropoiesis in the anemia of bone marrow failure

Alexanian¹,

Alfrey²

1970

J. Clin. Invest.

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A B S T R A CT The quantitative relationship between red cell volume, erythropoietin level, and erythropoiesis was evaluated in 43 human beings. Results in normal man were compared with studies in patients with anemia from bone marrow failure and with polycythemia vera. The maximum erythropoietin excretion after bleeding normal men was similar to the basal levels found in patients with chronic anemia of similar magnitude. Although erythropoietin values were low in patients with polycythemia vera, bleeding evoked a normal response. In patients anemic from bone marrow failure, basal levels were elevated, and phlebotomy resulted in an increase consistent with the new level of anemia. These observations indicate that erythropoietin level is affected primarily by the degree of anemia and is not influenced by the duration of anemia. In normal subjects, a fivefold increase in urinary erythropoietin was associated with a doubling of erythropoiesis. Despite similar degrees of erythropoietin production, anemic patients with evidence of bone marrow in the lower extremities had greater red cell production. In patients with polycythemia vera, red cell production was inappropriately elevated with regard to the urinary erythropoietin excretion. Bone marrow maturation time was not shortened in patients anemic from bone marrow failure to the same degree as in bled, normal volunteers. In addition to an adequate level of erythropoietin production, normal bone marrow function is necessary for maximal shortening of maturation time.

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Ferrokinetics: a biologic model for plasma iron exchange in man

Cited by 141 publications

References 16 publications

Serum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors

Serum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors

Marrow erythroid and neutrophil cellularity in the dog.

Erythropoiesis in the anemia of bone marrow failure

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