Anemia of chronic disease pathophysiology
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Inflammatory cytokines induce increased amounts of hepcidin by the liver. Hepcidin blocks ferroportin from releasing iron from the body stores. Inflammatory cytokines also decrease ferroportin expression and stops erythropoiesis by increasing bone marrow erythropoietin resistance. Apart from iron sequestration, white blood cells production is promoted by inflammatory cytokines. Bone marrow stem cells produce both red blood cells and white blood cells cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This may also have a role in inhibition of erythropoiesis, even when erythropoietin levels are normal, and aside from the effects of hepcidin.
- Inflammatory cytokines induce increased amounts of hepcidin by the liver. Hepcidin blocks ferroportin from releasing iron from the body stores.
- Inflammatory cytokines also decrease ferroportin expression and stops erythropoiesis by increasing bone marrow erythropoietin resistance.
- Apart from iron sequestration, white blood cells production is promoted by inflammatory cytokines. Bone marrow stem cells produce both red blood cells and white blood cells cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This may also have a role in inhibition of erythropoiesis , even when erythropoietin levels are normal, and aside from the effects of hepcidin.
- However, the combined effects of all the process are likely be in favor as it will allow the body to keep iron away from bacteria while the body boost the immune cell production.
- Sometimes, HIV infection and chronic kidney disease can lead to inflammation that can ultimately produce cytokines that can cause anemia of chronic disease.
Activated monocytes release cytokines like the interleukins (eg, IL-1 and IL-6) and tumor necrosis factor (TNF-alpha). These cytokines activate a cascade of reactions leading to the secretion of interferon (IFN)-beta and IFN-gamma by T lymphocytes leading to increased resistance of bone marrow to EPO.
Hepcidin is directly involved in iron metabolism and a component of the innate immune response to acute infection. It decreases the absorption of iron from small intestine, from placenta and from macrophages as well, secondary to its effect on internalization and degradation of the iron export protein ferroportin.
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