Anemia of Chronic disease
What is Anemia of chronic disease?
Anemia of chronic disease is a hypoproliferative anemia that develops in response to chronic illness or inflammation. Conditions associated with the anemia of infection and chronic inflammatory diseases include chronic bacterial endocarditis, osteomyelitis, juvenile rheumatoid arthritis, rheumatic fever, Crohn's disease, and ulcerative colitis. Chronic renal failure may produce a similar anemia because it causes reduced levels of erythropoietin, the hormone which stimulates the production of red blood cells in the bone marrow.
With anemia of chronic disease (ACD), the body cannot effectively use iron to make new red blood cells even though levels of stored iron in the body’s tissue are normal or high. As a result, the number of healthy new red blood cells gradually falls. Similarly, levels of hemoglobin, the component of red blood cells that carries oxygen to the tissues and muscles, also drop. Although ACD is the second most common form of anemia.
Anemia of chronic disease varies in severity. Patients typically present with mild (> 100 g/L) or moderate (85–100 g/L) reductions in hemoglobin concentrations. In a minority of patients, severe reductions can occur.
Pathophysiology of anemia of chronic disease
Three pathophysiologic mechanisms have been identified:
- Slightly shortened RBC survival occurs via unknown mechanisms in patients with cancer or chronic granulomatous infections.
- Erythropoiesis is impaired because of decreases in both erythropoietin (EPO) production and marrow responsiveness to EPO.
- Intracellular iron metabolism is impaired.
The pathophysiology of anemia of chronic disease begins with an erythropoietic defect that fails to increase the formation of erythrocytes in response to a rupture of the red blood cell, which releases hemoglobin into the plasma (hemolysis). Instead of accelerating its production, erythropoiesis continues at the normal rate. This failure may be caused by substances released from phagocytes, which tend to be numerous when inflammation or infection is present in the body.
LEM are caused by an abrupt drop in plasma iron levels. With long-term secretion of LEM, iron content apparently continues to decrease in plasma and to increase in the spleen and liver, as well as interfering with the iron cycle. This suggests that the cycle is disrupted at the point where iron released from macrophages of the mononuclear phagocyte system is returned to plasma. If this hypothesis is correct, LEM may consist of lactoferrin, an iron-binding protein normally present in neutrophils and body secretions.
Lactoferrin is nearly identical to transferrin, the protein that normally transports iron by binding it in plasma and carrying it to the marrow for erythropoiesis. However, lactoferrin has an iron-binding capacity 260 times greater than that of transferrin. When lactoferrin is present in the plasma, as occurs with increased levels of neutrophils in the blood, it competes with transferrin for the available iron molecules and wins. Iron that is bound to lactoferrin, instead of totransferrin, is removed by the MPS system instead of traveling to the marrow. Normally, lactoferrin in mucosal secretions prevents iron overload by preventing gastrointestinal absorption of iron. Its presence in plasma is apparently the result of increased levels of neutrophils in the blood caused by chronic inflammation, infection, or malignancy.