Iron deficiency

[Dr.Vad]

Уважаемые коллеги!

Последний номер журнала "Best practice and research in clinical haematology" посвящен "железным" проблемам: Volume 18, Issue 2, Pages 157-380 (June 2005); Iron Diseases; Edited by Chaim Hershko.

Будучи основным "промотором" на этом форуме по проблемам преимущественно железодефицита при различной соматической патологии, предлагаю Вашему вниманию некоторые из обзоров, посвященные наиболее клинически-ориентированным проблемам в терапии:

Diagnosis and management of iron-deficiency anaemia

James D. Cook MD, MSc (Med), Philips Professor of Medicine

Department of Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA

Anaemia is typically the first clue to iron deficiency, but an isolated haemoglobin measurement has both low specificity and low sensitivity. The latter can be improved by including measures of iron-deficient erythropoiesis such as the transferrin iron saturation, mean corpuscular haemoglobin concentration, erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or reticulocyte haemoglobin concentration. However, the changes in these measurements with iron deficiency are indistinguishable from those seen in patients with the anaemia of chronic disease. The optimal diagnostic approach is to measure the serum ferritin as an index of iron stores and the serum transferrin receptor as a index of tissue iron deficiency. The treatment of iron deficiency should always be initiated with oral iron. When this fails because of large blood losses, iron malabsorption, or intolerance to oral iron, parenteral iron can be given using iron dextran, iron gluconate or iron sucrose.

Definitions of impaired iron status
Laboratory diagnosis of iron deficiency
Screening measurements
Storage iron
Tissue iron
Clinical diagnosis of iron deficiency
Isolated iron deficiency
Iron deficiency with chronic disease
Defining the cause of iron deficiency
Physiological iron deficiency
Pathological iron deficiency
Treatment of iron deficiency
Oral iron therapy
Parenteral iron therapy
Iron dextran
Iron gluconate
Iron sucrose
Summary

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Iron requirements in erythropoietin therapy

Joseph Wetherill Eschbach MD, , Senior Research Advisor, Clinical Professor of Medicine, Emeritus

Northwest Kidney Centers, University of Washington, Seattle, WA, USA

When erythropoietin (epoetins or darbepoetin) is used to treat the anemias of chronic renal failure, cancer chemotherapy, inflammatory bowel diseases, HIV infection and rheumatoid arthritis, functional iron deficiency rapidly ensues unless individuals are iron-overloaded from prior transfusions. Therefore, iron therapy is essential when using erythropoietin to maximize erythropoiesis by avoiding absolute and functional iron deficiency. Body iron stores (800–1200 mg) are best maintained by providing this much iron intravenously in a year, or more if blood loss is significant (in hemodialysis patients this can be 1–3 g). There is no ideal method for monitoring iron therapy, but serum ferritin and transferrin iron saturation are the most common tests. Iron deficiency is also detected by measuring the percentage of hypochromic red blood cells, content of hemoglobin in reticulocytes, soluble transferrin receptor levels, and free erythrocyte protoporphyrin values, but iron overload is not monitored by these tests. Iron gluconate and iron sucrose are the safest intravenous medications.

Normal iron metabolism
Epoetin-responsive conditions
Iron metabolism in the anemia of chronic renal disease
Iron metabolism in other anemias
Functional iron deficiency
Effect of epoetin on iron metabolism in healthy subjects
Iron requirements associated with epoetin therapy
Chronic renal disease/failure
Cancer-related chemotherapy
Inflammatory bowel disease
Rheumatoid arthritis
Severe chronic heart failure
Monitoring iron therapy
Potential adverse effects of iron therapy
Summary

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Gastropathic sideropenia

Chaim Hershko MD,, Professor, Chief, Amnon Lahad MD and Dan Kereth MD

Department of Haematology, Shaare Zedek Medical Center, Hebrew University Hadassah Medical School, Jerusalem 91031, Israel
Department of Family Medicine, Clalit Health Services, Jerusalem, and Hebrew University Hadassah Medical School, Jerusalem, Israel
Department of Gastroenterology, Clalit Health Services, Jerusalem, and Hebrew University Hadassah Medical School, Jerusalem, Israel

There has been an increasing awareness recently of subtle, non-bleeding gastrointestinal conditions that may result in abnormal iron absorption leading to iron-deficiency anaemia (IDA) in the absence of gastrointestinal symptoms. Thus, the importance of coeliac disease as a possible cause of IDA refractory to oral iron treatment, without other manifestations of malabsorption syndrome, is increasingly being recognized. In addition, Helicobacter pylori has been implicated in several recent studies as a cause of IDA refractory to oral iron treatment, and the anaemia responds favourably to H. pylori eradication. Likewise, achlorhydric gastric atrophy or atrophic body gastritis (ABG), a condition associated with chronic idiopathic iron deficiency, has been shown to be responsible for refractory IDA in over 20% of patients with no evidence of gastrointestinal blood loss. It has also been suggested that H. pylori gastritis may represent an early phase of ABG in which infection may trigger an autoimmune process directed against gastric parietal cells by means of antigenic mimicry. In this review we examine in a critical manner the role of H. pylori gastritis in the causation of IDA, the role of ABG in the pathogenesis of iron malabsorption, the evidence supporting a possible cause-and-effect relationship between H. pylori gastritis and ABG, and the implications of these findings for the diagnostic work-up and management of IDA.

Helicobacter pylori and IDA
Population studies
Effect of H. pylori eradication on anaemia
Mechanism of iron deficiency in H. pylori gastritis
Occult gastrointestinal bleeding
Competition for dietary iron
Effect on gastric secretion
Atrophic gastritis and IDA
Possible role of H. pylori in the pathogenesis of ABG
Evidence based on population studies
Histological evaluation
Effect of H. pylori eradication
Prevalence of H. pylori and ABG in the diagnostic work-up of IDA
Implications for diagnostic work-up and management of IDA
References

[Dr.Vad]

The impact of iron fortification on nutritional anaemia

Sean R. Lynch MD, Professor of Clinical Medicine

Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA

Iron deficiency continues to be the most prevalent nutritional deficiency disorder in the world, affecting an estimated two billion people, most of whom live in developing countries. It has far-reaching effects on the health, well-being and productivity of those affected. Iron fortification of food is regarded as the most cost-effective method for reducing the prevalence of nutritional iron deficiency. In industrialized countries this has had an important beneficial effect; however, nutritional anaemia remains very prevalent in developing countries, and iron fortification appears until recently to have had little impact. Two important reasons for the latter situation are inadequate documentation of the magnitude of the iron deficiency component of anaemia in different regions of the world, and the use of iron compounds that are poorly bioavailable in fortification programmes. Several recent interventions using innovative approaches to dietary fortification that ensure the delivery of adequate quantities of bioavailable iron have demonstrated that iron fortification of food can be an effective and implementable strategy for controlling nutritional iron deficiency in non-industrialized countries.

Strategies for controlling nutritional iron deficiency
Impact of iron fortification on the reported prevalence of iron deficiency in industrialized countries
Specific evidence for an impact of mass fortification on prevalence of iron deficiency
Impact of fortification on the reported prevalence of iron deficiency in non-industrialized countries
Laboratory methods for documenting the prevalence of iron deficiency
Fortification methods
Successful fortification strategies in developing countries
Targeted fortification
Mass fortification
Potential risks of iron fortification
Summary and conclusions


In the World Health Report 2002 (‘Reducing Risks, Promoting Healthy Life’) nutritional iron deficiency was identified as one of the 10 leading risk factors for disease, disability and death in the world today, with an impact greater than that of either zinc or vitamin A deficiency. An estimated two billion people are affected, most of whom live in developing countries.

Adequate iron nutrition is assured only when the diet contains sufficient bioavailable iron to meet the requirements for growth and pregnancy, and to replace iron lost through menstruation, from the gastrointestinal tract and skin, and in the urine. Iron is present in most foods, and its intake is directly related to energy consumption. The risk for nutritional iron deficiency is therefore greatest when iron requirements are proportionately greater than energy needs in early childhood, at the time of the adolescent growth spurt, in women of childbearing age and during pregnancy.

Iron deficiency has a significant impact on the well-being of individuals as well as the productivity of societies. Pregnancy outcome is suboptimal, with increased risks for mothers and their babies including lower birth weight, increased infant mortality, and a greater risk for iron deficiency after the first 4 months of age. The mental and motor development of very young children may be delayed, with effects on behaviour and later academic performance during the school years. Failure to meet educational goals is likely to have a negative impact on earning power in adulthood. Physical work capacity is impaired at all ages. There are significant economic consequences for the individual, the family and the country, particularly where people's livelihoods depend on manual labour. Upper respiratory infections are more frequent and last longer in iron-deficient children. Finally, the response of endemic goitre to iodine supplementation may be suboptimal in populations that suffer from deficiencies of both iodine and iron.

The adverse effects of iron deficiency result from both impaired oxygen transport because of anaemia and the consequences of tissue iron deficiency that influences aerobic metabolism, protein synthesis, receptor function and many other metabolic processes. Tissue iron deficiency and anaemia become manifest simultaneously. There is a growing body of experimental evidence indicating that the effect of iron deficiency on psychomotor development in infancy results from the tissue iron deficit in the brain rather than the accompanying anaemia. Nevertheless, an effect of iron deficiency without anaemia on cognitive and motor development has not been established. On the other hand physical performance may be affected by iron deficiency in the absence of anaemia.

[Dr.Vad]

Дабы не открывать новый топик, некоторые недавние данные и отрывки обзоров, освещающие нарушения иммунитета у железодефицитных субьектов:

Hematol J. 2005;5(7):579-583.

The effect of iron deficiency anemia on the function of the immune system.

Ekiz C, Agaoglu L, Karakas Z, Gurel N, Yalcin I.

1Division of Hematology/Oncology, Department of Pediatrics, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.

We aimed to study the effect of iron deficiency anemia (IDA) on immunity. In 32 children with IDA and 29 normal children, the percentage of T-lymphocyte subgroups, the level of serum interleukin-6 (IL-6); and the phagocytic activity, the oxidative burst activity of neutrophils and monocytes and the levels of immunoglobulins were compared. There was no difference in the distribution of T-lymphocyte subgroups. The mean IL-6 levels was 5.6+/-3.9 pg/ml in children with IDA and 10.3+/-5.3 pg/ml in the control group (P<0.001). The percentage of neutrophils with oxidative burst activity when stimulated with pma was 53.4+/-32.7% in children with IDA and 81.7+/-14.3% in the control group (P=0.005). The percentage of monocytes with oxidative burst activity was 13.8+/-11.7% in children with IDA and 35+/-20.0% in the control group (P<0.001) when stimulated with pma. and 4.3+/-3.1 versus 9.7+/-6.0% (P=0.008) when stimulated with fMLP. The ratio of neutrophils with phagocytic activity was 58.6+/-23.3% in the anemic group; and 74.2+/-17.7% in the control group (P=0.057). The ratio of monocytes with phagocytic activity was 24.3+/-12.0% in the anemic group; and 42.9+/-13.4% in the control group (P=0.001). IgG4 level was 16.7+/-16.6 mg/dl in children with IDA and 51.8+/-40.7 mg/dl in healthy children (P<0.05). These results suggest that humoral, cell-mediated and nonspecific immunity and the activity of cytokines which have an important role in various steps of immunogenic mechanisms are influenced by iron deficiency anemia.

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Clin Immunol. 2004 Dec;113(3):340-4.

In vitro cytokine production in patients with iron deficiency anemia.

Bergman M, Bessler H, Salman H, Siomin D, Straussberg R, Djaldetti M.

Department of Medicine C, Rabin Medical Center, Golda Campus, Petah Tiqva 49372, Tel Aviv University, Ramat Aviv, Israel.

The in vitro production of interleukin (IL)-1beta, IL-2, IL-6, IL-10, and tumor necrosis factor alpha (TNFalpha) by peripheral blood mononuclear cells (PBMC) from 20 patients with iron deficiency anemia (IDA) was examined before and after iron supplementation and compared to values obtained for PBMC from healthy controls. A significant decrease in IL-2 production was observed in IDA patients, whereas the secretion of the other cytokines did not differ from that of controls.

IL-2 is essential for the proliferation of naive T lymphocytes and their differentiation into armed effector cells in the presence of specific antigen. Thus, it plays a central role in the host's normal immune response, stimulating cellular as well as humoral immune functions. In addition, IL-2 stimulates the growth and activity of NK cells, which in turn, kill virus- or bacteria-infected cells, as well as tumor cells. Therefore, a decrease in IL-2 production will impair the immune defense of the organism.
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Am J Clin Nutr. 2004 Mar;79(3):516-21.

Immune function is impaired in iron-deficient, homebound, older women.

Ahluwalia N, Sun J, Krause D, Mastro A, Handte G.

Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA.

In iron-deficient women, T cell proliferation upon stimulation with concanavalin A and phytohemagglutinin A was only 40-50% of that in iron-sufficient women. Phagocytosis did not differ significantly between the 2 groups, but respiratory burst was significantly less (by 28%) in iron-deficient women than in iron-sufficient women.

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[Dr.Vad]

Despite being the most abundant metal on earth, iron has a low bioavailability and iron deficiency remains the most common single nutrient deficiency worldwide. Iron deficiency is associated with alterations in many immunologic functions, most notably cell-mediated immunity. Most human studies report a decrease in the number of circulating T lymphocytes and in their blastogenic response to mitogens in iron deficiency.

The reduction in T lymphocytes is likely to be secondary to thymic atrophy, a condition that occurs in protein-energy malnutrition and zinc deficiency as well. In the latter conditions, the atrophy is a result of increased apoptosis induced by high levels of cortisol and perhaps decreased levels of leptin. Unlike human studies in which other nutrient deficiencies may confound the effects of iron deficiency, rodent studies have confirmed that pure iron deficiency can lead to thymic atrophy and reduced numbers of peripheral T lymphocytes. Kuvibidila et al. found that iron deficiency leads to depletion of total thymocytes without any significant differences in thymocyte subsets. However, in contrast to other states of malnutrition, iron deficiency is not associated with an increase in thymocyte apoptosis. Rather, thymocyte proliferation is less responsive to Concanavalin A and a higher percentage of thymocytes are found in the resting phase of the cell cycle. These changes do not appear to be related to changes in the production of the thymic hormone thymulin.

The role of iron in T cell development and autoimmunity.
Bowlus CL.Autoimmun Rev. 2003 Mar;2(2):73-8.
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In adult animals or humans with intact immune systems, nonspecific immunity is affected by iron deficiency in several ways. Macrophage phagocytosis is generally unaffected by iron deficiency, but bactericidal activity of these macrophages is attenuated. Neutrophils have a reduced activity of the iron-containing enzyme, myeloperoxidase, which produces reactive oxygen intermediates responsible for intracellular killing of pathogens. There is a decrease in both T-lymphocyte number and T-lymphocyte blastogenesis and mitogenesis in iron deficiency in response to a number of different mitogens. This alteration is largely correctable with iron repletion. Recent studies of T lymphocytes in iron deficiency noted that protein kinase C activity and translocation of both splenic and purified T cells were altered by iron deficiency.

Humoral immunity appears to be less affected by iron deficiency than is cellular immunity. In iron-deficient humans, antibody production in response to immunization with most antigens is preserved.

Из J Nutr. 2001 Feb;131(2S-2):568S-579S.
Iron biology in immune function, muscle metabolism and neuronal functioning.
Beard JL.

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[Dr.Vad]

В текущем NEJM March 10, 2005 опубликован обзор на тему:

Anemia of Chronic Disease. Guenter Weiss, M.D., and Lawrence T. Goodnough, M.D.

Краткое содержание:

Pathophysiological Features

Dysregulation of Iron Homeostasis

Impaired Proliferation of Erythroid Progenitor Cells

Blunted Erythropoietin Response

Laboratory Evaluation

Iron Status

Erythropoietin

Treatment

Rationale for Treatment

Treatment Options

Transfusion

Iron Therapy

Erythropoietic Agents

Monitoring Therapy

Conclusions