Clement A. Finch

A clinical evaluation of serum ferritin as an index of iron stores.

Abstract Measurements of serum ferritin were correlated with other hematologic laboratory indexes in 250 hospitalized subjects with anemia or disorders in iron metabolism. A geometric mean value of...

Thrombokinetics in man

Platelet production, distribution, and destruction have been quantitated in normal man and in selected patients with platelet disorders. In most instances, total production as calculated from the megakaryocyte mass agreed with production estimated from platelet turnover. In patients with megaloblastosis, a discrepancy between these two measurements indicated the presence of ineffective thrombopoiesis. Thrombopoiesis was regulated by (a) alterations in megakaryocyte number, and (b) changes in megakaryocyte volume (produced by changes in endomitosis). The volume-endomitosis changes were closely related to the peripheral platelet count and were a useful indicator of thrombopoietic stimulus. Thrombocytopenic disorders have been classified on the basis of the disturbed physiology into disorders of (a) production (hypoproliferative or ineffective), (b) distribution (splenic pooling), or (c) destruction (immune or consumptive). Less than a twofold increase in platelet production in the presence of significant thrombocytopenia was taken to represent impaired proliferation. Thrombocytosis was classified as reactive or autonomous. Reactive thrombocytosis was consistently associated with a mean megakaryocyte volume and endomitosis less than normal but appropriate for the elevated circulating platelet count. In contrast, the average megakaryocyte volume and nuclear number were always greater than normal in thrombocythemia findings indicating autonomy.

The diagnosis of iron deficiency anemia

Abstract Studies in a group of patients with iron deficiency anemia indicate that 16 per cent saturation of plasma transferrin or less implies an inadequate supply of iron to the erythroid marrow and is associated in time with hypochromic, microcytic anemia. In some patients with infection similar depressions in transferrin saturation were observed, and these were also associated with a decrease in red cell hemoglobin. It is further documented that decreased erythropoiesis, due to an inadequate iron supply, is not immediately associated with changes in cell indices and that an inadequate supply of iron to the individual cell has no relation to the total amount of blood being produced. Marrow hemosiderin has been shown, together with the circulating hemoglobin level, to be the best criterion for determination of total body iron, whereas it does not indicate the adequacy of iron supply to the marrow. Iron deficient erythropoiesis is defined as a state in which the supply of iron is inadequate to support optimal erythropoiesis in the developing red cell mass. This may occur as a result of depletion in total body iron or through an inadequate supply of plasma iron, which may be due either to a block in discharge of iron from the reticuloendothelial cell, as occurs in infection, or to absence of circulating transferrin. The best criterion of iron deficient erythropoiesis in this sense is the per cent saturation of transferrin. Sideroblast count has been shown to reflect not only iron supply, but hemoglobin synthesis by the red cells. A discrepancy in sideroblast count from that predicted by the iron supply (per cent saturation of transferrin) is a sensitive indication of a block in hemoglobin synthesis.

Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels

The relationship between oxygen dissociation and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in subjects moving from low to high altitude and vice versa. Within 24 hr following the change in altitude there was a change in hemoglobin affinity for oxygen; this modification therefore represents an important rapid adaptive mechanism to anoxia. A parallel change occurred in the organic phosphate content of the red cell. While this study does not provide direct evidence of a cause-effect relationship, the data strongly suggest that with anoxia, the observed rise in organic phosphate content of the red cell is responsible for increased availability of oxygen to tissues.

Body iron excretion in man: a collaborative study.

Abstract A collaborative study was undertaken in an attempt to document obligatory iron losses in adult male subjects, using a variety of isotopic and chemical methods. Total body excretion was measured in four groups of subjects by injecting Fe 55 intravenously and following the decline in red cell activity over several years. Calculated daily iron losses were as follows: Seattle white subjects (group I) 0.95 mg. (±0.30); Venezuelan Mestizos (group II) 0.90 mg. (±0.31); Johannesburg Bantu (group III) 2.42 mg. (±1.09); Durban Indians (group IV) 1.02 mg. (±0.22); and Durban Bantu (group V) 2.01 mg. (±0.94). The higher values in the Bantu subjects were ascribed to the greater than normal iron stores in this population group. That losses in the Durban Indian subjects, who were working in an extremely hot and humid environment, were not greater than those in the white subjects suggests that excessive sweating does not represent a major route for iron excretion. The results of isotopic experiments to determine the quantities of iron lost via the gastrointestinal tract suggested a daily loss of approximately 0.1 mg. within desquamated mucosal cells and 0.4 mg. in blood. Chemical analyses of bile indicated a mean daily content of 0.26 mg. However, it was not possible to establish what proportion of this iron is reabsorbed into the body. Direct chemical measurements of iron in urine revealed a mean daily content of approximately 0.1 mg.; this quantity did not seem to be influenced by the size of the body stores. The amount of iron taken up daily from the plasma by eccrine skin at normal transferrin saturations was between 0.2 and 0.3 mg. When the transferrin saturation was high this figure rose to between 0.6 and 0.7 mg. In a final analysis, the calculated iron losses from individual compartments were added together and compared with those obtained in the long-term excretion study. Agreement was close in all but the Bantu groups. Even when maximum figures for individual compartmental losses were used, the figures were still lower than those obtained for total excretion. These discrepancies may reflect methodologic errors but it is equally possible that subjects with overload lose iron in ways other than those examined in the present study, such as bile and/or iron-loaded reticuloendothelial cells shed into the lumen of the gastrointestinal tract.

Oxygen transport in man.

OXYGEN transport is a corporate process involving several organs, each with its own regulatory system. Individual diseases of the heart, lungs or blood may impair the functional capacity of a singl...

Food Iron Absorption Measured by an Extrinsic Tag

The paper describes the use of an extrinsic tag of inorganic radioiron to determine the total absorption of nonheme iron from a complete meal. The method was developed by measuring the iron absorbed from vegetable foods containing biosynthetically incorporated (55)Fe (intrinsic tag) and from (59)Fe added as a small dose of inorganic iron to the same meal (extrinsic tag). In studies with maize, black bean, and wheat, a consistent extrinsic: intrinsic radioiron absorption ratio averaging 1.10 was observed. Similar results were obtained with either ferrous or ferric iron as the extrinsic tag, and with doses of the latter ranging from 0.001 to 0.5 mg iron added to a test meal containing 2-4 mg of food iron. Adding the radioiron at different stages in preparation of the test meal also had little effect. Separate administration of the extrinsic tag was less satisfactory when small portions of a single food were employed, but with a complete meal, the separate dose was preferable. The extrinsic tag provided a valid measure of absorption despite marked differences in the iron status of the subject, and with wide changes in absorption imposed by adding desferrioxamine or ascorbic acid to the test meal. These findings indicate that there is a common pool of nonheme iron, the absorption of which is influenced by various blocking or enhancing substances present in the meal.

Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction.

Work performance on a treadmill has been evaluated in normal and iron-deficient rats. Anemia was removed as a variable by adjusting the hemoglobin of all animals to the same concentration. At a hemoglobin compatible with normal work performance, iron-deficient animals showed a marked impairment of running ability as compared to control animals. Iron therapy corrected the disability within 4 days. Concentrations of the cytochrome pigments and myoglobin, and rates of oxidative phosphorylation with pyruvate-malate, succinate, and alpha-glycerophosphate as substrates were all reduced in mitochondrial preparations from skeletal muscle of iron-deficient rats, but only the rate of phosphorylation with alpha-glycerophosphate as substrate increased significantly and in parallel with the recovery in work performance of the iron-deficient rats treated with iron dextran.

Intraerythrocytic adaptation to anemia.

Abstract The role of erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of hemoglobin oxygen in anemia was investigated. Measurements of 2,3-DPG and of oxygen dissociation (P50) were carried out on 57 normal subjects and 114 subjects with anemia. Twenty normal nonsmoking males had a mean hemoglobin of 15.3 g per 100 ml, a mean DPG of 4.83 mM and a mean P50 of 27.1 mm of mercury. Twenty normal nonsmoking females had a mean hemoglobin lower by 2.6 g per 100 ml, a DPG higher by 0.5 mM and a P50 increased by 0.4 mm of mercury DPG. P50 rose progressively with decreasing hemoglobin concentrations. For each gram of hemoglobin fall, there was a DPG increase of about 0.23 mM and a P50 increase of about 0.30 mm of mercury. Increases in adenosine triphosphate also occurred but, because of the smaller amount involved, had less effect on the oxygen dissociation curve. A rise in inorganic phosphate level had no demonstrable effect, but in vivo pH changes appear of considerable importance. It wa...

Idiopathic Hemochromatosis, an Interim Report

Experience over the last 20 years with 34 patients with idiopathic hemochromatosis is summarized and the literature is reviewed. Methods are now available which are highly effective in the diagnosis of iron overload and virtually all diagnoses are made antemortem. The nature of the disease has changed through the removal of iron by phlebotomy. Early deaths are limited to patients with severe and rapidly progressive heart disease and to those presenting with neoplasm. The major mortality has shifted to a much later period and the incidence of hepatoma is increasing. There is particular interest at the present time in family studies since excessive iron stores are frequently found within the family. The significance of intermediate degrees of iron overload is unclear, but future attention should be given to the recognition of iron overload long before clinical manifestations appear.