Chapter 098. Iron Deficiency and Other Hypoproliferative Anemias (Part 2)

Internal iron exchange.Normally about 80% of iron passing through the plasma transferrin pool is recycled from broken-down red cells. Absorption of about 1 mg/d is required from the diet in men, 1.4 mg/d in women to maintain homeostasis.As long as transferrin saturation is maintained between 20–60% and erythropoiesis is not increased, iron stores are not required. However, in the event of blood loss, dietary iron deficiency, or inadequate iron absorption, up to 40 mg/d of iron can be mobilized from stores. RE, reticuloendothelial.The iron-transferrin complex circulates in the plasma until it interacts with specific transferrin receptors on the surface...
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Chapter 098. Iron Deficiency and Other Hypoproliferative Anemias (Part 2) Chapter 098. Iron Deficiency and Other Hypoproliferative Anemias (Part 2)Figure 98-1 Internal iron exchange. Normally about 80% of iron passing through the plasma transferrin pool isrecycled from broken-down red cells. Absorption of about 1 mg/d is required fromthe diet in men, 1.4 mg/d in women to maintain homeostasis. As long as transferrin saturation is maintained between 20–60% anderythropoiesis is not increased, iron stores are not required. However, in the eventof blood loss, dietary iron deficiency, or inadequate iron absorption, up to 40 mg/dof iron can be mobilized from stores. RE, reticuloendothelial. The iron-transferrin complex circulates in the plasma until it interacts withspecific transferrin receptors on the surface of marrow erythroid cells. Diferrictransferrin has the highest affinity for transferrin receptors; apotransferrin(transferrin not carrying iron) has very little affinity. While transferrin receptorsare found on cells in many tissues within the body—and all cells at some timeduring development will display transferrin receptors—the cell having the greatestnumber of receptors (300,000 to 400,000/cell) is the developing erythroblast. Once the iron-bearing transferrin interacts with its receptor, the complex isinternalized via clathrin-coated pits and transported to an acidic endosome, wherethe iron is released at the low pH. The iron is then made available for hemesynthesis while the transferrin-receptor complex is recycled to the surface of thecell, where the bulk of the transferrin is released back into circulation and thetransferrin receptor reanchors into the cell membrane. At this point a certainamount of the transferrin receptor protein may be released into circulation and canbe measured as soluble transferrin receptor protein. Within the erythroid cell, ironin excess of the amount needed for hemoglobin synthesis binds to a storageprotein, apoferritin, forming ferritin. This mechanism of iron exchange also takesplace in other cells of the body expressing transferrin receptors, especially liverparenchymal cells where the iron can be incorporated into heme-containingenzymes or stored. The iron incorporated into hemoglobin subsequently enters thecirculation as new red cells are released from the bone marrow. The iron is thenpart of the red cell mass and will not become available for reutilization until thered cell dies. In a normal individual, the average red cell life span is 120 days. Thus, 0.8–1.0% of red cells turn over each day. At the end of its life span, the red cell isrecognized as senescent by the cells of the reticuloendothelial (RE) system, andthe cell undergoes phagocytosis. Once within the RE cell, the hemoglobin fromthe ingested red cell is broken down, the globin and other proteins are returned tothe amino acid pool, and the iron is shuttled back to the surface of the RE cell,where it is presented to circulating transferrin. It is the efficient and highlyconserved recycling of iron from senescent red cells that supports steady state (andeven mildly accelerated) erythropoiesis. Since each milliliter of red cells contains 1 mg of elemental iron, theamount of iron needed to replace those red cells lost through senescence amountsto 16–20 mg/d (assuming an adult with a red cell mass of 2 L). Any additional ironrequired for daily red cell production comes from the diet. Normally, an adultmale will need to absorb at least 1 mg of elemental iron daily to meet needs, whilefemales in the childbearing years will need to absorb an average of 1.4 mg/d.However, to achieve a maximum proliferative erythroid marrow response toanemia, additional iron must be available. With markedly stimulatederythropoiesis, demands for iron are increased by as much as six- to eightfold.With extravascular hemolytic anemia, the rate of red cell destruction is increased,but the iron recovered from the red cells is efficiently reutilized for hemoglobinsynthesis. In contrast, with intravascular hemolysis or blood loss anemia, the rateof red cell production is limited by the amount of iron that can be mobilized fromstores. Typically, the rate of mobilization under these circumstances will notsupport red cell production more than 2.5 times normal. If the delivery of iron tothe stimulated marrow is suboptimal, the marrows proliferative response isblunted, and hemoglobin synthesis is impaired. The result is a hypoproliferativemarrow accompanied by microcytic, hypochromic anemia. While blood loss or hemolysis places a demand on the iron supply,conditions associated with inflammation interfere with iron release from stores andcan result in a rapid decrease in the serum iron (see below). ...