Anemia of chronic disease

Anemia of inflammation is associated typically with normal iron stores within normal transf2242ing saturation.

Anemia of chronic disease is largely explained by elevated hepcidin production in response to inflammatory cytokines.

Systemic inflammation and cancer leads to the production of inflammatory cytokines such as  IL-6, IL-10,  and and interferon-gamma which have broad effects on red blood cell production, lifespan, and iron metabolism.

In an inflammatory state RBC damage occurs by free radical mediated injury as well as immune complex and fibrin deposition, which increase RBC phagocytosis a distraction by macrophages.

This process leads to iron retention in macrophages an increase f2242itin production and the blockage of iron export as a result of the elevation of iron exporter f2242oportin production.

Like iron deficiency anemia, it is characterized by low serum iron levels, but differs in that iron stores are preserved in marrow macrophages, as well as in splenic and hepatic macrophages that recycle senescent erythrocytes.

Hypof2242emia and increase production of leukocytes serve host defense at the expense of erythrocyte production and erythrocyte survival, decreasing the number of erythrocyte precursors and macrophage activation shortens RBC lifespan.

It is a disorder primarily of iron distribution.

Hypof2242emia develops within the first few hours after infection or other inflammatory processes with decrease in the plasma iron level and transferin saturation which serves to prevent the generation of nontransf2242in-bound iron, an iron species recognized as potent stimulus to the pathogenicity of gram-negative bacteria, and other microbes as well.

Hypof2242emia associated with increased plasma f2242itin and hepcidin levels is characteristic of anemia of inflammation , whereas in iron deficiency anemia, hypof2242emia is associated with a low plasma f2242itin and hepcidin levels.

Hypof2242emia has an inhibitory effect on erythropoiesis.

Erythropoiesis is inhibited by hypof2242emia at a saturation of 15-20% and protects the iron supply for other tissues such as muscle, CNS, and non erythroid marrow which are less affected by decreased plasma iron levels.

Erythropoiesis represents the main consumer of iron from the plasma, and the recycling of senescent red cells by macrophages is the main source of iron for plasma.

High levels of circulating hepcidin stimulated by interleukin-6, inhibits the export of cellular iron into plasma, decreasing both intestinal absorption of iron and a release of iron from erythrocyte-recycling macrophages in the spleen and liver.

Associated with an increased serum f2242itin and decreased total iron-binding capacity (TIBC).

A hypoproliferative disease that can resolve if the underlying disease is corrected.

Most common causes are acute and chronic infections, malignancies, autoimmune diseases, chronic kidney disease and chronic rejection after solid organ transplant.

Immune driven by cytokines and reticuloendothelial system cells that cause changes in iron homeostasis, decrease proliferation of red blood cell progenitors, impair production of erythropoeitin, and decrease lifespan of red blood cells.

Serum iron is depressed in anemia of chronic illness because proinflammatory cytokines that induce hepatic synthesis of hepcidin which decreases intestinal iron absorption and release of iron from macrophages.

Hepcidin levels are markedly increased as a response to chronic inflammation.

Hepcidin binds to f2242oportin, a transport protein that is essential for the transition of iron out of cells and therefore blocks both absorption from the gut and egress from macrophages.

Hepcidin synthesis is controlled by feedback from both iron stores and plasma iron levels.

Iron homeostasis is deranged with increased amounts of iron stored in duodenal enterocytes and in macrophages of the bone marrow,and liver-spleen.

Iron laden macrophages cause increased levels of f2242itin in the serum.

Erythroid precursors in the bone marrow have decreased cytoplasmic iron, and red blood cells that enter the circulation are smaller than normal.

Red blood cell production suppression results in a low reticulocyte index.

While erythrocytes in iron deficiency anemia are often small with a low mean corpuscular volume, and hemoglobin deficient with low mean corpuscular hemoglobin concentration, the erythrocytes in inflammation most often appear normal, or they will they become small and pale in a subset of patients, particularly those in whom iron deficiency coexists or develops as a complication.

Anemia of chronic inflammation is rarely severe, and in patients with hemoglobin of less than 8 g/dL other contributors to anemia must be considered.

The bone marrow’s response to early inflammatory changes is to promote leukocytosis and increase production of leukocytes with an increased number of myeloid precursors with the ratio of myeloid to erythroid precursors of greater than 4:1.

The bone marrow reprogramming in inflammation is related to cytokines su has TNF-alpha and interferon-gamma which promote myelopoiesis and lymphopoiesis at the expense of erythropoiesis.

Bone marrow reprogramming is also mediated by inflammatory suppression of erythropoietin.

Serum erythropoietin levels are decreased in patients with systemic inflammation, particularly as compared with patients of a similar degree of iron deficiency anemia.

The responsiveness of red blood cell precursors to erythropoietin is impaired by inflammation.

In the anemia of inflammation, there is an approximate 25% decrease in the red blood cell lifespan, to approximately 90 days.