Description

• Anemia that accompanies a variety of systemic diseases, with the common features of chronicity and inflammation
• Anemia of chronic disease is more properly called anemia of inflammation (AI) and is the combined result of mildly increased destruction of RBCs, relative erythropoietin resistance, and iron-restricted erythropoiesis.

Pathophysiology

Typically mild to moderate anemia (Hgb 7 to 12 g/dL); develops in the setting of infection, inflammatory disorders, and some malignancies

• Deficient cellular iron in the setting of hepcidin excess (functionally inaccessible iron)
• Typically normochromic, normocytic but, if long-standing, can be hypochromic, microcytic (especially in children)
• Main mechanism appears to be
  • Hepcidin is increased by interleukin-6 (IL-6), causing depletion of ferroportin, the only known membrane iron transporter.
  • Elevated hepcidin results in macrophage inability to release iron recycled from senescent RBCs, hepatocyte inability to release stored iron, and enterocyte inability to absorb dietary iron.
  • These changes lead to iron restriction with decreased iron available for erythropoiesis.
• Other factors contributing to anemia in various degrees include the following:
  • Increased red cell destruction
  • Diagnostic phlebotomy or other blood loss
  • Inflammatory cytokines suppress erythropoiesis
  • Cytokine-mediated suppression of erythropoiesis
  • Cytokines such as interleukin-1 (IL-1) and IL-6 can activate ferritin synthesis, leading to sequestration of iron, which eventually is converted into hemosiderin.

Etiology

Underlying disease process

Commonly Associated Conditions

• Underlying disease process
  • Infections, both acute and chronic
  • Inflammatory disease
  • Collagen vascular diseases
  • Malignancies
  • Renal failure
• Anemia of chronic disease often coexists with other causes of anemia, including:
  • Occult blood loss
  • Hemolysis
  • Dietary iron deficiency
  • Drug-related marrow suppression