Anemia of chronic disease pathophysiology: Difference between revisions
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==Overview== | |||
==Pathophysiology== | |||
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]]. | |||
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. | |||
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. | |||
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. | |||
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. | |||
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. | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Disease]] | [[Category:Disease]] | ||
Revision as of 14:54, 21 September 2012
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Differentiating Anemia of chronic disease from other Diseases | |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
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.
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.
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.
In the short term, the overall effect of these changes is likely positive: it allows the body to keep more iron away from bacterial 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.
Because anemia of chronic disease can be the result of non-bacterial causes of inflammation, future research is likely to investigate whether hepcidin antagonists might be able to treat this problem.
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 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.