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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adequacy of tissue iron supply was examined with ferrokinetic techniques in subjects with decreased plasma iron concentration and in subjects with a normal plasma iron concentration but with increased tissue iron requirements. The competition by transferrin receptors for diferric vs monoferric transferrin was measured in eight normal persons and eight with iron deficiency. There was a highly significant (P less than 0.001) decrease in receptor preference for diferric transferrin in subjects with iron deficiency, indicating an insufficient amount of iron-bearing transferrin to saturate tissue receptors. The adequacy of the plasma iron supply was also examined by determining the number of iron-bearing transferrin molecules with receptors at normal and elevated plasma iron concentrations. Significant increases were found at the higher plasma iron concentration, not only in patients with iron deficiency, but also in patients with sickle cell anemia and thalassemia. Furthermore, the increase in the latter two groups was shown to be proportional to the degree of erythroid hyperplasia. These data indicate that tissue iron supply must be evaluated in terms of both plasma iron supply and erythropoietic requirements and that a relative iron deficiency is frequent in patients with erythroid hyperplasia.
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PMID:Adequacy of iron supply for erythropoiesis: in vivo observations in humans. 368 Nov 15

The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.
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PMID:The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein. 378 68

To determine the quantitative effects of iron deficiency on erythropoiesis and to assess the response of erythroid progenitors to sustained anemia, we developed quantitative assays for various hematopoietic progenitors in the adult, Sprague-Dawley rat including erythroid colony- and burst-forming cells (CFU-E and BFU-E), granulocyte/macrophage colony-forming cells (CFU-GM), and megakaryocytic colony-forming cells (CFU-Meg). CFU-E were cultured in methylcellulose and grew best in the presence of fetal calf serum. CFU-GM, BFU-E, and CFU-Meg grew better in normal rat plasma and required the presence of pokeweed mitogen-stimulated rat spleen cell conditioned medium. The numbers of progenitors and nucleated erythroblasts in total marrow were estimated by the ratios of radioactivity in the humerus to the total skeleton as determined by radioiron dilution. The numbers of progenitors and erythroblasts in the spleen were measured by simple dilution. Sustained anemia was brought about through chronic iron deficiency. The response to iron deficiency anemia (IDA) was monitored by the numbers of the various progenitors and their cell cycle characteristics as measured by the tritiated thymidine suicide technique. With IDA, the number of CFU-F in the body (marrow plus spleen) was increased to 3.5 times control, whereas the numbers of BFU-E and CFU-GM were unchanged. There was no difference in the percentage of CFU-E, BFU-E, and CFU-GM in DNA synthesis (68%, 19.4%, and 18.8%, respectively). With iron therapy of IDA, CFU-E numbers in marrow began to decrease by day 1 and fell in a manner reciprocal to changes in the hematocrit. Marrow and spleen erythroblasts, 1.7 times control in IDA, increased further to 3.9 times control by the fourth day after iron administration. There was no change in BFU-E or CFU-GM numbers in response to iron repletion, although the fraction of progenitors increased in the spleen. Thus, IDA does not limit the increase in CFU-E seen with anemia, but does restrict erythroid maturation. Furthermore, the increase in CFU-E and the state of chronic anemia occur without detectable changes in the number of cell cycle state of the more primitive BFU-E.
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PMID:Hematopoiesis in the rat: quantitation of hematopoietic progenitors and the response to iron deficiency anemia. 394 11

The character and pathogenesis of hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse, were studied. The main hematological features of hemoglobin deficit are anemia, red cell hypochromia and microcytosis, and reticulocytosis. The absence of raised fecal urobilinogen excretion and frank hyperbilirubinemia and bilirubinuria suggests that excess hemolysis is not the primary cause of the anemia. The raised plasma iron concentration and the failure of the anemia to respond to parenteral iron treatment indicate that the anemia is not due to iron deficiency. The absence of siderocytes and sideroblasts suggests that anemia is probably not due to ferrochelatase deficiency. Thalassemia is excluded by the finding of balanced reticulocyte globin chain synthesis. The markedly elevated levels of free red cell protoporphyrin taken together with the other findings already noted suggest that the anemia of hemoglobin deficit is due to a defect in the erythroid cell iron procurement mechanisms leading in turn to diminished heme and hemoglobin synthesis.
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PMID:Hemoglobin deficit: an inherited hypochromic anemia in the mouse. 396 Aug 59

Marrow hypoplasia is described in CBA/H mice that drank water containing 300 mg/liter cadmium chloride for 12 months. This was characterized by a significant reduction of the totipotent stem cells (CFU-s), granulocyte-monocyte progenitor cells (GM-CFUc), and erythroid progenitor cells (CFU-e). The bone marrow cellularity and the proliferative capacity of GM-CFUc in vitro were decreased. The animals reflected these marrow alterations by demonstrating an anemia with reticulocytopenia and neutropenia. They did not show increased mortality or increased susceptibility to infections; however, their body weight was significantly reduced. In addition, iron deficiency was demonstrated in the cadmium-treated mice. The animals had a hypochromia of the peripheral red cells and diminished marrow iron stores. Thus, the anemia of cadmium toxicity is probably the combined result of bone marrow hypoplasia and iron deficiency.
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PMID:Long-term oral cadmium produces bone marrow hypoplasia in mice. 397 72

Bilirubin-(14)C production was measured in rats transfused with labeled erythrocytes from animals with iron deficiency anemia, a condition associated with ineffective erythropoiesis. With labeled reticulocytes harvested 1 day after the administration of glycine-2-(14)C, conversion of hemoglobin-(14)C to bilirubin averaged 47.3% over the 3 days of observation; the corresponding value for reticulocytes from normal rats was only 1.7%. Findings were not altered by splenectomy. Bilirubin-(14)C production fell to 35.8% with iron-deficient cells harvested 3 days after glycine-(14)C administration, and declined further to a plateau averaging 25% with cells labeled 5, 7, 10, or 15 days earlier. The latter values still far exceed those for mature erythrocytes from normal animals.The findings indicate that experimental iron deficiency anemia is associated with hemolysis of red cells of various ages, but with preferential destruction of the youngest cells. Degradation of hemoglobin from reticulocytes is sufficient to account for a major fraction of the increase in erythropoietic bilirubin production found in this disorder, as has also been shown for physiologically regulated erythroid hyperplasia. However, the defect is quantitatively much more striking in experimental iron deficiency, and this and perhaps a similar defect in bone marrow cells appear to explain the decrease in net hemoglobin production that is characteristic of pathologic ineffective erythropoiesis.
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PMID:Preferential hemolysis of immature erythrocytes in experimental iron deficiency anemia: source of erythropoietic bilirubin formation. 556 91

Macrogranulocytic and/or erythroid megaloblastic bone marrow changes which could not be accurately predicted from the hematologic findings in the blood were present in 25% of 305 mildly to moderately anemic pregnant women attending a public antepartum clinic in Montreal. Iron deficiency was the primary cause of anemia in most instances. Serum folate activity of less than 4.1 ng./ml. and/or serum vitamin B(12) levels of less than 100 pg./ml. were present in 90% of the 77 patients having these bone marrow changes, whereas approximately one-third of 228 patients with normoblastic marrow had these low values. Red cell folate did not correlate as well as serum folate activity with bone marrow changes. After treatment with oral folic acid in the range of 0.2 mg. to 0.8 mg., daily, for seven to 14 days, the megaloblastic and macrogranulocytic changes in patients with low serum folate activity and normal serum vitamin B(12) values disappeared in 15 of 21 patients. Of five women having both low folate and vitamin B(12) values, three failed to respond and two showed only partial improvement after 0.4 mg. of folic acid daily, per os, for 10 days. The average diet of these anemic women was suboptimal in folate and in iron.
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PMID:Nutritional anemia and megaloblastosis in pregnancy. 590 44

Erythrocyte protoporphyrin (EP) was measured in 50 normal control subjects, 22 iron-responsive anemic subjects, and in 106 patients with thalassemic diseases. All normal subjects had EP of less than 80 micrograms/dL red blood cells, whereas all iron-deficiency subjects had EP of more than 80 micrograms/dL red blood cells. Six of 22 heterozygotes for thalassemias had elevated EP, and all of these had transferrin iron saturation of less than 16%, reflecting a complicating iron deficiency. Among 52 patients with beta-thalassemia/hemoglobin (Hb) E disease, 26.9% had elevated EP levels, and among 32 patients with Hb H disease, 40.6% had elevated EP. These elevated EP levels were associated with transferrin iron saturation between 18 and 44%. In none of the thalassemic patients with transferrin iron saturation above 44% was EP elevated. These findings suggest that elevation of EP in some thalassemic patients causally is related to iron supply inadequate for the massively expanded erythropoiesis. This relative iron deficiency in thalassemia occurs at a transferrin iron saturation level usually considered to be normal. These relationships demonstrate the need for an increased iron supply in patients with erythroid marrow hyperplasia, if erythropoiesis is to proceed at maximal rates.
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PMID:Increased red blood cell protoporphyrin in thalassemia: a result of relative iron deficiency. 646 95

Red cell ferritin was measured in normal subjects and patients with disorders of iron metabolism, inflammation, liver dysfunction, impaired hemoglobin synthesis, and increased red cell turnover by means of radioimmunoassays with antibodies to liver (basic) and heart (acidic) ferritins. The normal mean values for basic and acidic ferritin were 8.9 and 22.7 altogram (ag)/cell, respectively. The red cell ferritin content reflected changes occurring in tissues both in iron deficiency and iron overload. Basic ferritin was more closely related to the body iron status than acidic ferritin, and the acidic/basic ferritin ratio was increased in iron deficiency and decreased in iron overload. The major factor determining the red cell ferritin content appeared to be the transferrin saturation, that is, the distribution of iron between monoferric and diferric transferrin. This is in keeping with recent data indicating a competitive advantage of diferric transferrin in delivering iron to erythroid cells. In addition, the red cell ferritin content was increased in thalassemic patients with normal iron status, appearing to be inversely related to the rate of hemoglobin synthesis. The determination of red cell ferritin, based on a commercially available basic ferritin assay, can have clinical application. It can be used for evaluating the adequacy of the iron supply to the erythroid marrow, particularly in patients with increased red cell turnover. Moreover, it may be useful in evaluating the body iron status in patients with hemochromatosis and liver disease.
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PMID:Biologic and clinical significance of red cell ferritin. 662 42

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.
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PMID:Inadequate erythroid response to hypoxia in cystic fibrosis. 673 32


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