Anemia of chronic disease is a mild-to-moderate anemia associated with chronic infections, chronic non-infectious inflammatory diseases, and malignancies.
This type develops after a month or two of active disease; and its severity is related to that of the underlying disorder, but it may also be asymptomatic or a coincidental finding.
Chronic disease anemia is usually normocytic-normochromic; but it may also be normocytic-hypochromic, or microcytic-hypochromic (See Anemia Types for definitions.).
Anemia of chronic disease has fewer and milder clinical manifestations than most other anemias, but it depends on the degree of the anemia. This type of anemia does not respond to iron replacement therapy because the iron is unable to reach the bone marrow. Therefore, the treatment of choice is the alleviation of the underlying disorder. The anemia itself does not require treatment unless it becomes symptomatic.
Three mechanisms are generally responsible for anemia of chronic disease:
- decreased erythocyte life span,
- failure of mechanisms of compensatory erythropoiesis, and
- disturbances of the iron cycle
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. These substances, known collectively as “leukocyte endogenous mediator (LEM)” or “leukocyte pyrogen”, are released by neutrophils and macrophages.
Research indicates that LEM causes 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 MPS (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.
In cancers, an extrinsic factor may accelerate erythrocyte destruction. Several attempts have been made to identify such a factor. Cancer researchers have suggested four possibilities:
- Hemolytic agents (hemolipins) are released from the tumor.
- Erythrocytes are destroyed by entering the tumor.
- The tumor stimulates the immune system to produce antibodies against erythrocyte antigens.
- Erythrocytes are destroyed by macrophages activated by the disease.
Chronic renal failure is another chronic disorder affected by anemia, and appears to result from several factors:
- a shortened life span of RBCs caused by some extracorpuscular factor associated with the uremic state;
- impaired RBC production resulting from decreased production of erythropoietin;
- an increased tendency to bleed associated with a prolonged bleeding time, probably related to impaired platelet function;
- superimposed nutritional anemia.
Because the anemia associated with renal failure is related to a decreased production of erythropoietin, it usually cannot be successfully managed with hematinic agents (used to improve the quality of the blood). However, sufficient sources of folic acid and iron should be provided in the diet, although this is difficult when protein sources are restricted.
Inadequate intake and iron losses that may occur are managed by supplemental iron. Providing adequate sources of vitamin C at the same time that iron-rich foods or supplements are given, enhances its absorption.
Wound healing can become a chronic condition that simultaneously fights infection while trying to heal an open area. Some wounds take months or years to heal and since wound healing relies on oxygen supplies from the blood, anemia can slow the process because oxygen supply to the tissues is reduced.
Anemia of chronic infection is commonly associated with such diseases as rheumatoid arthritis, systemic lupus erythematosus (and other autoimmune collagen disorders), Hodgkin’s disease, colitis, and regional enteritis.
However, few stop to realize that it can also happen as a result of seemingly common and such less serious infections as urinary tract infections, a head or chest cold, tonsillitis or strep throat, stomach or intestinal flu, as well as bacterial infections. Because this type of anemia is associated with so many pathologic conditions, it is likely second only to iron deficiency anemia in overall incidence.
Infection caused by a toxin from an infective agent, usually a microorganism, can sometimes inhibit the production of red cells by the bone marrow. While these bacteria, viruses, fungi, or parasites are known to produce disease, long term infections can eventually cause such secondary conditions as anemia.
At the onset of an infection, blood iron rapidly declines as iron moves into the liver for storage. This shift helps fight the infection by depriving the infecting microorganisms of the body’s iron, which they may require for their own metabolism. However, along with this life-saving mechanism also comes the inability to make new hemoglobin, resulting in anemia.
This type of anemia reflects the body’s normal physiological response to infection and does not respond to iron, folic acid (B9), or vitamin B12 supplementation or to any other dietary or medical treatment.
In fact, providing large doses of iron, or other nutrients, can actually worsen the infection as the microorganisms gain strength by feeding on the supplements intended for the host.
Without any intervention, the liver will eventually return iron to the blood as the infection resolves.
