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14: Iron (Chapter 17)

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    Abstract

    Dietary iron is present as heme and non­heme iron, each absorbed by dif­fer­ent mech­anisms. Once absorbed, the iron released can be stored or bound to plasma trans­ferrin for distribution to other tissues. Quantitatively, most iron is used by immature red blood cells in the bone marrow for hemo­globin (Hb) produc­tion. Senescent erythrocytes are degraded by macrophages, and the iron released from catabolized Hb re-enters the circu­lation. Absorption of iron is modulated in response to the level of body iron stores and by the amount of iron needed for erythro­poiesis. Hepatic hepcidin is the master regulator of iron homeo­stasis. Hepcidin levels are suppressed by iron depletion or increased iron demand (i.e., enhanced erythro­poiesis), thereby increasing absorp­tion and mobilization of iron from body stores into plasma. In contrast, when iron stores are replete (and during inflam­mation), hepcidin levels are increased, so iron cannot efflux into the circu­lation, thus preventing iron overload.

    Anemia is the most common sign of iron deficiency in low- and middle-income countries, with with infants, young children, and women of child-bearing age at greatest risk. Features of iron defi­ciency anemia (IDA) include impairments in work capacity and cognition, and possibly risk during preg­nancy of low birth­weight and prem­aturity. Despite low specificity and sensitivity, a low Hb concen­tration is the most widely used test for IDA. Devel­opment of IDA occurs in three stages, the first being a decrease in iron stores, reflected by a low serum ferritin, followed by iron-deficient erythro­poiesis. At this stage, iron stores are exhausted (i.e., serum ferritin < 12µg/L), iron supply to the erythro­poietic cells is progressively reduced, and decreases in trans­ferrin satu­ration occur. At the same time, serum soluble trans­ferrin receptor (sTfR) and erythrocyte proto­porphyrin increase. Only in the third stage is there a decline in Hb, decreases in hematocrit and red-cell indices, and frank microcytic, hypo­chromic anemia, confirmed by examination of a stained blood film.

    This chapter describes how to assess the adequacy of dietary iron intakes, followed by details of the hematological parameters used to diagnose anemia, the serum bio­markers to identify iron depletion (serum ferritin), and iron deficient erythro­poiesis (serum ferritin; serum iron; trans­ferrin satu­ration; sTfR; and erythrocyte protoporphyrin). Advantages and limitations are discussed together with details of the measure­ment and interpretive criteria for each bio­marker. Use of a regression modeling approach to adjust for the effect of inflam­mation on serum ferritin and sTfR is highlighted, in view of the challenge of distin­guishing between IDA and anemia of chronic disease. The final section emphasizes the simul­tane­ous use of multiple iron bio­markers to provide a more valid assessment of iron status and minimize misclassification that may occur when using a single measure. The advantages of using the “Total Body Iron Model” based on serum ferritin and sTfR expressed as body iron (mg/kg), with a cutoff of < 0mg/kg to define iron defi­ciency, is described. Finally, details of emerging iron indicators, notably hepcidin, non-trans­ferrin-bound iron, and some reticulocyte indices, are presented.

    • 14.1: Introduction and functions of iron (17.1)
      This page discusses the importance of assessing iron status due to widespread deficiency, primarily affecting vulnerable groups and contributing to anemia. It details mechanisms of iron absorption (heme vs. non-heme), regulatory factors, and the impact of diet and micronutrients. The page highlights the significance of dietary iron fortification, the use of algorithms for assessing iron needs, and the complexities of iron overload and supplementation.
    • 14.2: Hemo­globin (17.2)
      This page discusses anemia and hemoglobin (Hb) concentrations, detailing various factors influencing Hb levels, such as altitude, smoking, diseases, and genetic disorders. It highlights the importance of appropriate Hb cutoff values for anemia diagnosis, particularly emphasizing the need for age-specific adjustments for vulnerable populations. Additionally, it covers measurement techniques for Hb, advocating for standardized methods to ensure accurate diagnoses across diverse settings.
    • 14.3: Hematocrit or packed cell volume
      This page covers hematocrit, a measure of the percentage of packed red blood cells in blood, influenced by factors such as age and sex, with males typically showing higher levels post-puberty. Pregnancy decreases hematocrit due to increased plasma volume. While it serves as an alternative to hemoglobin measurements, its accuracy can be limited. Hematocrit can be measured manually or with automated counters, though results may differ.
    • 14.4: Red-cell indices
      This page examines red-cell indices, crucial for diagnosing anemia, particularly iron deficiency. Derived from hemoglobin and hematocrit measurements, these indices vary based on anemia type and require fresh blood samples for accuracy. While automated machines have improved readings, further tests like serum iron and ferritin are necessary due to their lack of specificity.
    • 14.5: Red-cell distribution width (17.5)
      This page discusses RDW, a measurement of red blood cell size variation included in a complete blood count. Increased RDW can indicate conditions such as iron-deficiency anemia, folate, or vitamin B12 deficiencies. Classifying anemia by RDW is complicated due to varying cutoffs and disease presentations. RDW percentile distributions are available from studies in the U.K. and New Zealand, and research suggests age-specific cutoffs may be required as RDW tends to increase with age.
    • 14.6: Serum iron, TIBC, trans­ferrin, and trans­ferrin satu­ration (17.6)
      This page discusses the key variables for diagnosing iron status, focusing on serum iron, TIBC, transferrin saturation, and serum ferritin. High biological variation necessitates multiple evaluations for accuracy, particularly in the presence of factors like age, sex, chronic diseases, and obesity, which can distort results. Furthermore, comparisons between normal-weight and overweight/obese women reveal higher iron demands and inflammation in the latter group.
    • 14.7: Serum ferritin (17.7)
      This page discusses the complexities of assessing iron status through serum ferritin levels, which are influenced by age, sex, race, inflammation, and health conditions like obesity and liver disease. Elevated ferritin can misrepresent iron deficiency, especially during inflammation or pregnancy. The BRINDA approach offers improved assessment by considering inflammatory factors.
    • 14.8: Erythrocyte protoporphyrin
      This page discusses heme synthesis, highlighting the role of zinc in substituting iron, leading to zinc protoporphyrin (ZPP) accumulation. It emphasizes measuring erythrocyte protoporphyrin (EP) for assessing iron deficiency with varying efficiency based on age, sex, and health conditions, complicated by factors like inflammation and lead poisoning. Pediatric reference ranges for EP are noted, alongside differences in measurement methodologies and cutoffs.
    • 14.9: Serum soluble trans­ferrin receptor (17.9)
      This page emphasizes the role of serum soluble transferrin receptor (sTfR) as a marker for iron status, highlighting its increased levels during iron deficiency and low biological variation. However, its reliability diminishes in pregnancy due to erythropoietic changes and in contexts with concurrent conditions like malaria or hemoglobin disorders.
    • 14.10: Multiple bio­markers (17.10)
      This page discusses the assessment of iron status using multiple biomarkers, particularly serum ferritin and serum transferrin receptor (sTfR). A combination of these indicators offers more accurate evaluations of iron deficiency across different stages. The WHO recommends specific biomarkers, adjusting for inflammation, with a focus on the sTfR to ferritin ratio for better clarity.
    • 14.11: Emerging iron status indicators (17.11)
      This page discusses emerging diagnostic indicators for iron status such as hepcidin, reticulocyte indices, and non-transferrin-bound iron (NTBI), noting their research basis and need for clinical validation. Hepcidin regulates iron but may increase deficiency risks in obesity and varies significantly in different health contexts, including its impact during pregnancy and disease.

    This page titled 14: Iron (Chapter 17) is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by Rosalind S. Gibson via source content that was edited to the style and standards of the LibreTexts platform.