Anemia - Introduction

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The process leading to ACD may occur in the following way:

• The immune system activates white blood cells and releases various compounds during times of infection that are intended to fight invaders and heal wounds. Such an event causes an inflammatory state in the areas of the attack.
• White blood cells called macrophages release small but powerful proteins known as cytokines, which are critical in the development of ACD. Cytokines are indispensable for healing. However, cytokines are overproduced often in chronic and inflammatory diseases, causing serious tissue injury and, in some cases, even organ damage. In the case of ACD, they prevent production of erythropoietin, the hormone that acts in the bone marrow to increase the production of red blood cells. Specific cytokines implicated in anemia are interleukin 1 (IL-1), tumor necrosis factor (TNF), and interferons.
• As part of this process, mechanisms prevent the release of recycled iron needed in the bone marrow for the manufacturing of red blood cells. Iron absorption in the intestines is also blocked. Theoretically, this is a protective measure, since iron may help infectious organisms proliferate. In such cases, iron stores are high, but the usable iron in circulation is low.
• Researchers have identified a peptide called hepcidin, which prevents iron absorption in the intestine and blocks the release of iron by immune factors for red blood cell production. Some experts believe high levels of the peptide may play a central role in preventing the release of iron during infection and inflammatory states, and is critical in ACD.

Diseases Associated with ACD and Inflammation. The chronic diseases that are associated with this process include:

• Certain cancers. Examples include lymphomas and Hodgkin's disease.
• Autoimmune diseases. Examples include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and polymyalgia rheumatica.
• Long-term infections. Examples include urinary tract infections and osteomyelitis. Common childhood infections, such as ear infections and urinary tract infections, may even cause anemia due to inflammation. (This anemia often resolves on its own but may be confused with iron deficiency.)
• Hepatitis C. The liver cirrhosis associated with hepatitis C can reduce the production of red blood cells. Gastrointestinal bleeding may also contribute to blood loss.
• Heart failure. Experts estimate that 25 – 60% of patients with heart failure also have anemia. However, it is unclear whether anemia actually causes or worsens heart failure. Recent research suggests it may actually be a sign (marker) of heart failure. Iron deficiency in heart failure can be due to a number of factors. It may be caused by a lack of nutrients in a person’s diet or by the body’s inability to absorb nutrients from food. Heart failure can also cause a back up of fluid (edema). This edema produces a higher volume of blood plasma (the liquid part of blood), which can dilute red blood cells and cause anemia.
• Chronic kidney disease. The hormone erythropoietin (EPO) is produced in the kidneys and stimulates the bone marrow production of red blood cells. Diseased kidneys do not release sufficient amounts of EPO; anemia can result and is universal in end-stage renal disease. Chronic kidney disease is a common complication of diabetes.
• HIV/AIDS. The inflammatory process associated with AIDS can adversely affect EPO levels and red blood cell production.
• Anemia in critically ill patients. Evidence suggests similarities between ACD and severe anemia in patients who are in intensive care. Some experts believe that the cause of anemia in such critically ill patients may also be due to inflammatory responses that promote impaired responsiveness to erythropoietin.