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

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated from the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.
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PMID:Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation. 250 4

The currently accepted concept of iron absorption proposes first the entry of iron into the intestinal mucosal cell through the brush border membrane. It is a relatively slow process. In the cell, the iron may be transferred to plasma or become sequestered by ferritin. The latter becomes unavailable for transfer to plasma and is exfoliated and excreted. In iron deficiency and idiopathic hemochromatosis, the rate of iron uptake into the intestinal mucosal cell is increased and entry into ferritin is decreased, whereas the rate of transfer to plasma remains constant. The reverse occurs in case of secondary iron overload. It is currently accepted that a transferrin, whose levels increase in iron deficiency, enters the intestinal lumen from the liver via bile, where it may sequester iron and bring it into the cells by the process of endocytosis. Iron presented as inorganic ferric or ferrous salts may also be absorbed, though the more soluble ferrous salts are adsorbed much more rapidly. Heme iron is absorbed very effectively, though it is not subject to regulation by the individual's iron status to the same extent as is inorganic iron absorption. Brush border membranes apparently contain saturable iron receptors for inorganic iron, but whether or not the absorption process requires energy is an open question. Absorption of iron may also be affected by its availability; different food components affect iron absorbability to a different extent.
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PMID:Biochemistry of nonheme iron in man. II. Absorption of iron. 266 38

Fluorescently labeled antibodies were used to identify transferrin receptors and mucosal transferrin in human gastrointestinal biopsy sections. Transferrin receptors were evident in the villous epithelium and the crypt areas of duodenum, ileum, and colon, predominantly in the basal-lateral area. In 7 subjects with low iron stores, the intensity of duodenal villous staining for receptor, on a scale of 0-4, was 2.1 +/- 0.3 (mean +/- SD). This value was significantly higher than the value in 13 subjects with normal iron stores (1.1 +/- 0.4). In 5 patients with hereditary hemochromatosis, duodenal transferrin receptor staining was not significantly different from that in the subjects with normal iron stores. Transferrin staining was found in the apical cytoplasm of epithelial cells in the duodenum, ileum, and colon, but observer assessment was not sufficiently reproducible to make a quantitative analysis. Our results suggest that iron deficiency is accompanied by an increase in transferrin receptors in duodenal absorptive cells, and the genetic lesion in hemochromatosis does not involve an increase in transferrin receptors in the intestinal mucosa compared with subjects with normal iron stores.
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PMID:Transferrin receptors in the human gastrointestinal tract. Relationship to body iron stores. 301 5

There is increasing evidence that both iron overload and iron deficiency are associated with significant abnormalities of immune function. In diseases associated with iron overload there is increased susceptibility to both infection and neoplasia. The precise mechanisms are still being unravelled but iron overload has been shown to impair antigen-specific immune responses and to reduce the number of functional helper precursor cells. Similarly, iron in vitro in concentrations reported to be present in the serum of patients with iron overload impairs the generation of cytotoxic T-cells, enhances suppressor T-cell activity and reduces the proliferative capacity of helper T-cells. The predominant tumor seen in iron overload is primary hepatocellular carcinoma; however other aetiological factors appear to be involved in addition to iron overload, especially hepatic cirrhosis. Nevertheless, primary liver cancer occurs much more frequently in hemochromatosis than in other forms of cirrhosis. Iron deficiency is associated with an altered response to infection but the relationship is again a complex one. The cellular mechanisms involved have yet to be clearly defined, although impaired T and B cell function have been demonstrated.
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PMID:Iron status and cellular immune competence. 328 53

Iron absorption is under delicate control and the level of absorption is adjusted to comply with the body's need for iron. To measure the intestinal setting for iron absorption, and thereby indirectly assess body iron requirements, cobaltous chloride labelled with (57)Co or (60)Co was given by mouth and the percentage of the test dose excreted in the urine in 24 hours was measured in a gamma counter. Seventeen control subjects with normal iron stores excreted 18% (9-23%) of the dose. Increased excretion, 31% (23-42%), was found in 10 patients with iron deficiency anemia and in 15 patients with depleted iron stores in the absence of anemia. In contrast, 12 patients with anemia due to causes other than iron deficiency excreted amounts of radiocobalt within the normal control range. In patients with iron deficiency, replenishment of iron stores by either oral or parenteral iron caused the previously high results to return to normal.Excretion of the test dose was normal in portal cirrhosis with normal iron stores but it was markedly increased in patients with cirrhosis complicated by either iron deficiency or endogenous iron overload. It was also raised in primary hemochromatosis. Excretion of the dose was reduced in gluten-sensitive enteropathy. Gastrointestinal surgery and inflammatory disease of the lower small intestine had no effect on the results except that some patients with steatorrhea had diminished excretion.The cobalt excretion test provides the clinician with a tool for the assessment of iron absorption, the detection of a reduction in body iron stores below the level that is normal for the subject in question, the differentiation of iron deficiency anemia from anemia due to other causes, and the investigation of patients with iron-loading disorders.
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PMID:Cobalt excretion test for the assessment of body iron stores. 557 25

The rate of absorption of iron is adjusted according to body iron requirements, but the virtual absence of heme and the poor bioavailability of the nonheme iron in the diets of many people, especially in developing countries, means that the amount that can be absorbed is limited. Those whose requirements are increased by growth, menstruation, or pregnancy frequently cannot absorb enough. Sufficient is now known about the factors in food that increase or diminish the bioavailability of nonheme iron to permit the effective fortification of dietary staples, although the application of this information has proved difficult particularly in the Third World where nutritional iron deficiency is most prevalent. Effective fortification may lead to iron overload in those whose control of iron absorption is genetically defective, and recent evidence that the HLA-linked recessive gene for idiopathic hemochromatosis may occur much more commonly than hitherto suspected makes it imperative that an effective monitoring system should form a part of every fortification program.
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PMID:Iron absorption. 634 77

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

In healthy persons the plasma ferritin concentration is a sensitive index of the size of body iron stores. It has been successfully applied to large-scale surveys of the iron status of populations. It has also proved useful in the assessment of clinical disorders of iron metabolism. A low plasma ferritin level has a high predictive value for the diagnosis of uncomplicated iron deficiency anemia. It is of less value, however, in anemia associated with infection, chronic inflammatory disorders, liver disease and malignant hematologic diseases, for which a low level indicates iron deficiency and a high level excludes it, but intermediate levels are not diagnostic. Measuring the plasma ferritin concentration is also useful for the detection of excess body iron, particularly in idiopathic hemochromatosis, but again it lacks specificity in the presence of active hepatocellular disease. If iron overload is suspected in these circumstances determination of the iron content of a percutaneous liver biopsy specimen is required. In families with idiopathic hemochromatosis the combined determination of the plasma ferritin concentration and the transferrin saturation is a sufficient screen to identify affected relatives; however, estimation of the hepatic iron concentration is required to establish the diagnosis.
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PMID:Plasma ferritin concentrations: their clinical significance and relevance to patient care. 699 66

The accurate measurement of ferritin in the serum was first reported in 1972. Since then, the assay has become widely available to clinicians. However, the role of this assay in the diagnosis and treatment of various diseases is still poorly defined. Serum ferritin levels are clearly useful in the diagnosis of simple iron deficiency. Hepatic disease, malignancies, and other chronic diseases can cause an elevation in serum ferritin which does not represent an elevation in body iron stores. While markedly elevated in late hemochromatosis, the value of serum ferritin in the detection of early hemochromatosis or the carrier state is not certain.
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PMID:Clinical applicability and usefulness of ferritin measurements. 700 34

The nature of iron in the serum of patients with idiopathic hemochromatosis has been studied utilizing an isotope labeling method and results have been compared with those from normal individuals and patients with other forms of liver disease. Between 2 and 4% of a tracer dose of 59Fe added to normal serum was retained by DEAE Sephadex and has been designated non-transferrin-bound. Alcoholic liver disease, chronic active hepatitis, and iron deficiency have no effect on this fraction. In idiopathic hemochromatosis 34.6 +/- 3.9% of the added iron was not bound to transferrin at diagnosis, representing approximately 700 microgram Fe/liter serum. Treatment lowers this fraction before serum iron concentration falls to normal. The majority of the non-transferrin-bound iron is of low molecular weight and is not bound to albumin. The presence of this fraction may contribute significantly to the development of tissue siderosis.
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PMID:A non-transferrin-bound serum iron in idiopathic hemochromatosis. 737 72


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