What is Anemia of Chronic Disease?
Anemia of chronic disease (ACD), also known as anemia of inflammation, is a prevalent type of anemia that occurs in patients with chronic inflammatory conditions, infections, or malignancies. It is characterized by a low production of
red blood cells due to the body's response to these persistent conditions.
How Does Inflammation Affect Red Blood Cell Production?
In chronic inflammatory states, cytokines such as
interleukin-6 and
tumor necrosis factor-alpha are released, which can interfere with the production of erythropoietin, a hormone critical for red blood cell production. Additionally, these cytokines can promote the sequestration of iron in macrophages by increasing the synthesis of
hepcidin, a peptide hormone that inhibits iron absorption and release.
What are the Histological Features of Anemia of Chronic Disease?
Histologically, ACD is characterized by a normocytic, normochromic anemia, although it can sometimes present as microcytic anemia due to restricted iron availability. Bone marrow biopsy in these patients typically shows normal or increased
iron stores in macrophages, reflecting the sequestration of iron within reticuloendothelial cells, despite low serum iron levels.
How is ACD Differentiated from Iron Deficiency Anemia in Histology?
While both ACD and iron deficiency anemia can present with low serum iron, they exhibit distinct histological features. In ACD, bone marrow aspirate often shows abundant iron stores within macrophages, whereas iron deficiency anemia is characterized by depleted iron stores. Additionally,
serum ferritin levels are usually normal or elevated in ACD, whereas they are low in iron deficiency anemia.
What Role Do Macrophages Play in ACD?
Macrophages play a critical role in the pathophysiology of ACD. They store iron in the form of ferritin and hemosiderin, limiting its availability for erythropoiesis. Under the influence of hepcidin, macrophages reduce the release of iron into the circulation, further contributing to anemia. This sequestration of iron is a protective mechanism to limit its availability to infectious agents and tumor cells during chronic disease states.What is the Role of Hepcidin in ACD?
Hepcidin is central to the regulation of iron homeostasis. In ACD, hepcidin levels are elevated due to inflammatory cytokines. It binds to and degrades the iron exporter
ferroportin on the surface of enterocytes and macrophages, reducing intestinal iron absorption and iron release from macrophages, respectively. This leads to the characteristic iron-restricted erythropoiesis of ACD.
How Does ACD Affect Red Blood Cell Lifespan?
In ACD, the lifespan of red blood cells may be slightly reduced due to increased phagocytosis by macrophages in response to inflammatory signals. However, the primary issue is not premature destruction but rather inadequate production of red blood cells due to iron sequestration and impaired erythropoietin response.What are the Treatment Strategies for ACD?
Treatment of ACD involves addressing the underlying chronic condition. In some cases, erythropoiesis-stimulating agents (ESAs) may be used to stimulate red blood cell production. Iron supplementation is often ineffective unless coexistent iron deficiency is present, due to the high levels of hepcidin inhibiting iron absorption. Anti-inflammatory treatments may also help in reducing cytokine levels and improving anemia.Conclusion
Anemia of chronic disease is a complex condition that reflects the body's intricate response to chronic inflammation. Histologically, it is distinguished by iron sequestration and impaired erythropoiesis, with macrophages playing a pivotal role. Understanding the underlying mechanisms, particularly the role of hepcidin, is crucial for developing effective treatment strategies.
