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Article Excerpt
Iron is critical to the functioning of all cells in the body and is the most essential nutrient for the creation of healthy erythrocytes with adequate hemoglobin content. One of the primary roles of iron is to carry oxygen as part of hemoglobin. If iron is not present for developing erythrocytes, hemoglobin synthesis is impaired, resulting in anemia and reduced oxygen delivery to body tissues (Fauci et al., 2008).
Iron deficiency, leading to low hemoglobin levels, is a pervasive problem in patients with end stage renal disease (ESRD) on hemodialysis (HD). Anemia due to various forms of iron deficiency and restricted iron availability is associated with an increased risk of morbidity and mortality, as well as reduced quality of life. Therefore, it is important for nephrology nurses to understand the basics of iron physiology, including how iron is absorbed and transported by the body to the erythroid marrow to be incorporated into hemoglobin. It is also essential for nurses to understand how the normal state of iron balance that exists in the healthy individual is altered in the patient on HD, and what the best strategies are for repleting iron stores and maintaining iron balance. A glossary of important terms used throughout this article can be found in Table 1.
Normal Iron Balance in the Healthy Individual
In the healthy individual, iron absorption, transport, and storage are regulated in a tightly controlled system. This system serves several functions: it effectively delivers iron to the bone marrow for hemoglobin building and erythrocyte production; it transports iron to and from storage sites in the macrophages of the reticuloendothelial (RE) system and the hepatocytes of the liver; it recycles iron from senescent (i.e., dying) erythrocytes; and it protects the body from free iron, which participates in chemical reactions that generate free radicals that may be potentially harmful to the body (Fauci et al., 2008).
Iron Distribution in the Body
Adult men have about 25 to 45 mg of iron per kg of body weight (approximately 3000 to 4000 mg). Pre-menopausal women have somewhat lower iron stores (Andrews, 1999). This iron is distributed into several compartments in the body (see Figure 1) (Andrews, 1999). Of the body's total iron content, more than half is incorporated into the hemoglobin of circulating erythrocytes. Another 1000 mg is stored in the cells of various organs, primarily the liver. The macrophages of the RE system contain about 600 mg of iron. An additional 300 mg of iron is incorporated into the muscle cells as myoglobin, which serves as an intracellutar storage site for oxygen and is used for metabolic purposes.
Finally, about 300 mg of iron at any given time is contained in the bone marrow, where most of it is actively being incorporated into hemoglobin. Iron forms the basis for hemoglobin production in erythrocytes, which are produced in the erythroid tissues of the bone marrow (together, the circulating erythrocytes in the blood, their precursors, and all the body elements concerned in their production are known as the erythron).
Iron Absorption
Iron in the diet is absorbed by enterocytes, which are specialized epithelial cells that take up iron as it passes through the duodenum (Fauci et al., 2008). Nearly all absorption of dietary iron occurs in the duodenum (Fleming & Bacon, 2005), although a small amount is taken up elsewhere along the tract of the small intestine. Iron entering the duodenum is moved across the cell wall of the enterocyte by a divalent metal transporter (DMT-1) (Fauci et al., 2008). Iron that enters the enterocyte is either released from the cell into the circulation through a transmembrane iron transporter known as ferroportin or is stored within the cell. Iron stored within the enterocyte is subsequently lost when the cell dies and is sloughed from the wall of the intestine.
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Circulating Iron
Iron released into the circulation binds to transferrin, a small protein produced by the liver with 2 iron-binding sites (Fauci et al., 2008). Transferrin is the body's iron-transport vehicle, and it shuttles iron between those cells that are able to release iron (the enterocytes, the RE macrophages of the liver and spleen, and the hepatocytes of the liver) and those cells that are able to take up iron through transferrin receptors (e.g., the developing erythrocytes of the bone marrow and the hepatocytes of the liver) (Andrews, 1999; Fauci et al., 2008). In healthy individuals, about 20% to 50% of the total iron-binding sites on transferrin are occupied by iron at any given time. This amount of iron bound to transferrin is known as the percentage of transferrin saturation (TSAT), one of the primary measures of iron status (National Kidney Foundation [NKF], 2006).
Iron actively bound to transferrin is known as the functional iron pool. The functional iron pool represents a very small amount of the body's total iron--about 3 mg--but it is incredibly active. Transferrin takes up and turns over its iron 10 to 20 times a day, and the uptake of iron from transferrin in the presence of iron deficiency can be as short as 10 to 15 minutes (Fauci et al., 2008).
Iron that is delivered to the various body compartments (i.e., muscle, liver, and bone marrow) is either utilized or stored. In the muscle, iron is incorporated into myoglobin. In the bone marrow, the majority of iron is incorporated into hemoglobin in developing erythrocytes. Mature erythrocytes enter the circulation, where they have a life span of approximately 120 days. Dying, or senescent, erythrocytes are engulfed by RE macrophages, where hemoglobin is broken down, and the iron is separated out and recycled back over to transferrin.
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Iron Storage
Iron in excess of that incorporated into hemoglobin or turned over to transferrin by the macrophages is stored within a protein complex known as tissue ferritin. Iron is also stored within tissue ferritin in the cells of the liver. In cases where transferrin-bound iron is low, iron can be released from its stores inside tissue ferritin and maned over to transferrin as needed. A second form of ferritin, called serum ferrifin, is also produced in conjunction with tissue ferritin. Serum ferritin is an indirect measure of iron stores and is another measure used to assess a patient's iron status (NKF, 2006). Serum ferritin originates from the release of tissue ferritin, contains little or no iron, and its role is less clearly understood (Cavill, 1999; Easom, 2006).
Iron in Red Blood Cell Production
Within the erythroid marrow, adequate and healthy erythrocyte production depends on the presence of both iron and erythropoietin (EPO). Erythropoietin is a hormone produced primarily by the kidneys, with a small amount produced by the liver. It is secreted in response to the level of tissue oxygenation in the kidneys, with low oxygen levels (e.g., in the case of anemia) encouraging its production. Once stem cells in the erythroid marrow have "committed" to developing into erythrocytes, the primary roles of EPO are to stimulate the production of these erythroid progenitor cells and to protect them from apoptosis (programmed cell death) (see Figure 2) (Fauci et al., 2008; Petroff, 2005). In patients...
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