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| {{SK}} Anemia of inflammation | | {{SK}} Anemia of inflammation |
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| ==Overview==
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| '''Anemia of chronic disease''', increasingly referred to as "anemia of inflammation", is a form of [[anemia]] seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy. New discoveries suggest that the syndrome is likely primarily the result of the body's production of [[hepcidin]], a master regulator of [[human iron metabolism]].
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| ==Pathophysiology==
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| In response to inflammatory [[cytokines]], the liver produces increased amounts of [[hepcidin]]. Hepcidin in turn stops [[ferroportin]] from releasing iron stores. Inflammatory cytokines also appear to affect other important elements of iron metabolism, including decreasing [[ferroportin]] expression, and probably directly blunting [[erythropoiesis]] by decreasing the ability of the [[bone marrow]] to respond to [[erythropoietin]].
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| Before the recent discovery of [[hepcidin]] and its function in iron metabolism, anemia of chronic disease was seen as the result of a complex web of inflammatory changes. Many investigators still hold this view while adding hepcidin to their description of this complexity, while others appear to feel that hepcidin is likely to be the most important factor in producing the condition. (Contrast, for example, the tone of the referenced articles by Andrews vs. Weiss and Goodnough, below.) Hepcidin offers an attractive [[Occam's Razor]] explanation for the condition, but not enough experiments have been performed to establish yet whether it alone can account for the changes of anemia of chronic disease.
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| For instance, in addition to effects of iron sequestration, inflammatory cytokines promote the production of [[white blood cells]]. [[Bone marrow]] produces both [[red blood cells]] and [[white blood cells]] from the same precursor [[stem cells]]. Therefore, the upregulation of [[white blood cells]] causes fewer [[stem cells]] to differentiate into [[red blood cells]]. This effect may be an important cause for the effective inhibition of [[erythropoiesis]] described earlier, even when [[erythropoietin]] levels are normal, and even aside from the effects of hepcidin.
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| In the short term, the overall effect of these changes is likely positive: it allows the body to keep more iron away from [[bacteria]]l pathogens in the body, while producing more immune cells to fight off infection. Bacteria, like most life forms, depend on iron to live and multiply. However, if inflammation continues, the effect of locking up iron stores is to reduce the ability of the [[bone marrow]] to produce [[red blood cells]]. These cells require iron for their massive amounts of [[hemoglobin]] which allow them to transport oxygen.
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| Because anemia of chronic disease can be the result of non-bacterial causes of inflammation, future research is likely to investigate whether hepcidin [[Receptor_antagonist|antagonists]] might be able to treat this problem.
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| Anemia of chronic disease as it is now understood is to at least some degree separate from the anemia seen in [[renal failure]] in which anemia results from poor production of [[erythropoietin]], or the anemia caused by some drugs (like [[zidovudine|AZT]], used to treat [[HIV]] infection) that have the side effect of inhibiting [[erythropoiesis]]. In other words, not all anemia seen in people with chronic disease should be diagnosed as anemia of chronic disease. On the other hand, both of these examples show the complexity of this diagnosis: HIV infection itself can produce anemia of chronic disease, and renal failure can lead to inflammatory changes that also can produce anemia of chronic disease.
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| ==Diagnosis==
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| Anemia of chronic disease is often a mild [[Anemia#Normocytic_anemia|normocytic anemia]], but can sometimes be more severe, and can sometimes be a [[microcytic anemia]]; thus, it often closely resembles iron-deficiency anemia. Indeed, many people with chronic disease can also be genuinely [[iron deficiency|iron deficient]], and the combination of the two causes of anemia can produce a more severe anemia. As with iron deficiency, anemia of chronic disease is a problem of red cell production. Therefore, both conditions show a low [[reticulocyte production index]], suggesting that [[reticulocyte]] production is impaired and not enough to compensate for the decreased red blood cell count.
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| While no single test is always reliable to distinguish the two causes of disease, there are sometimes some suggestive data:
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| * In anemia of chronic disease without iron deficiency, [[ferritin]] levels should be normal or high, reflecting the fact that iron is stored within cells, and ferritin is being produced as an [[acute phase reaction|acute phase reactant]] but the cells are not releasing their iron. In [[iron deficiency anemia]] ferritin should be low.
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| * [[TIBC]] should be high in genuine iron deficiency, reflecting efforts by the body to produce more [[transferrin]] and bind up as much iron as possible; [[TIBC]] should be low or normal in anemia of chronic disease.
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| If the importance of [[hepcidin]] in this condition is borne out, tests to measure hepcidin or cellular expression of [[ferroportin]] may one day be useful, but neither are available as [[validate|validated]] clinical [[assays]].
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| Examination of the bone marrow to look for the absence or presence of iron, or a trial of iron supplementation (pure iron deficiency anemia should improve markedly in response to iron, while anemia of chronic disease will not) can provide more definitive diagnoses.
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| ==Treatment==
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| The ideal treatment for anemia of chronic disease is to treat the chronic disease successfully. Barring that, many patients with anemia of chronic disease simply live with the effects of the anemia as part of enduring the limits placed on them by other aspects of their underlying medical conditions. In more severe cases, [[transfusions]] or several versions of commercially-produced [[erythropoietin]] can be helpful in some circumstances; both approaches are costly.
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| ==References==
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| *[http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=15124013 Andrews NC. Anemia of inflammation: the cytokine-hepcidin link. ''Journal of Clinical Investigation'' 113(9):1251-3. May 2004.]
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| *Weiss G and Goodnough LT. Anemia of chronic disease. ''New England Journal of Medicine'' 352(10):1011-1023. March 10, 2005. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15758012&query_hl=2 PMID: 15758012]
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| *Schrier, SL. Anemia of chronic disease (anemia of chronic inflammation). [http://www.uptodate.com Up-to-Date] (requires subscription). Accessed December 2005.
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| ==External Links== | | ==External Links== |