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Chapter 445 Anemia of Chronic Disease and Renal Disease
445.1 Anemia of Chronic Disease
Norma B. Lerner
The anemia of chronic disease (ACD), also referred to as “anemia of inflammation,” is found in conditions where there is chronic immune activation. This anemia thus complicates a number of systemic diseases associated with infection (e.g., HIV, bronchiectasis, osteomyelitis) or autoimmunity (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease) as well as some hematologic and solid malignancies. Despite diverse underlying causes, the erythroid abnormalities are similar, although incompletely understood. Erythrocytes have a mildly decreased life span, felt to be, at least in part, secondary to erythrophagocytosis by activated macrophages. However, it is the relative failure of the bone marrow to respond adequately to the increased destruction that perpetuates the anemia. Erythropoietin (EPO) levels are modestly increased but are often inadequate. More importantly, inflammation induces a blunted response and relative resistance to EPO.
Another contributing factor is decreased iron availability. Inflammation causes iron retention by the reticuloendothelial system, creating limited availability for erythropoiesis. The serum iron is low, although tissue macrophages have abundant iron. Iron availability is further compromised by decreased intestinal absorption. One hypothesis has been that the underlying medical conditions cause the release of inflammatory cytokines, interleukin-1 (IL-1), tumor necrosis factor (TNF), and interleukin-6 (IL-6), which lead to the production of interferon-β (IFN-β) and interferon-γ (IFN-γ). This hypothesis is supported by the observation that IFN-β and IFN-γ cause a disorder in experimental animals similar to the anemia of chronic disease. IL-6 induces the production of hepcidin, an iron-regulating protein. Hepcidin, which is made in the liver, blocks the release of iron from macrophages and also decreases intestinal iron absorption. Its increased production and the associated decrease in iron availability lead to an impairment of heme synthesis and ultimately to decreased proliferation of erythroid precursors.
Although the important symptoms and signs associated with anemia of chronic disease are those of the underlying disease, the mild to moderate anemia can affect the patient’s quality of life.
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