Anemia of Chronic Disease

Overview
  • Anemia of Chronic Disease is an anemia that can manifest as either microcytic or normocytic in morphology and occurs in contexts of chronic inflammation due to dysregulation of iron mobilization.
Pathophysiology
  • Anemia of Chronic Disease can arise in the context of a large number of chronic inflammatory states and specific etiologies are discussed below. Whatever the particular cause, these chronic inflammatory states result in the production of a variety of inflammatory cytokines that dysregulate iron homeostasis at multiple steps and ultimately yield a de facto state in which iron is unavailable for erythropoiesis even though total body iron stores may be relatively normal.
  • The most important defect of iron homeostasis in inflammatory states is an inability to mobilize ferritin-bound iron stored within hepatocytes and reticuloendothelial macrophages. This not only makes the body's normal reservoir of iron unavailable for use, but also prevents iron derived from recycled senescent erythrocytes to be mobilized.
  • Additionally, inflammatory cytokines appear to reduce intestinal iron absorption, reduce renal erythropoietin secretion, and render the bone marrow more resistant to the actions of erythropoietin.
Laboratory Consequences
  • Given the inability of ferritin-bound iron stores to be mobilized, serum ferritin levels are classically normal-to-high in anemia of chronic disease. This is also exacerbated by the fact that ferritin is an acute phase protein and thus is produced at higher levels in inflammatory states. In contrast, serum iron levels are also typically low in anemia of chronic disease and Total Iron Binding Capacity (TIBC) in the serum may be relatively low or sometimes normal.
Morphology
  • The morphology of the erythrocytes produced in anemia can overlap significantly with those found in iron deficiency anemia. Erythrocytes may be small in anemia of chronic disease (i.e. microcytic), but can also be of relatively normal size (i.e. normocytic). Typically, cells are less dense (i.e. hypochromic) but their variability in size (i.e. Poikilocytosis) is not as pronounced as that found in iron deficiency anemia. Because of this morphological similarity, peripheral smears are not useful in distinguishing anemia due to chronic disease from iron deficiency. Rather, serum levels of ferritin are the most useful distinguishing feature: High in anemia of chronic disease but low in iron deficiency.
Etiologies
  • Any disease state which results in chronic inflammation can yield anemia of chronic disease. Therefore chronic infections, malignancies, and rheumatic diseases are frequently to blame.
Clinical Consequences
  • Anemia of Chronic Disease shares the same basic clinical consequences as those of any other anemia (See page).