Anemia Of Chronic Diseases (14) Flashcards
How does a problem with heme or globin synthesis lead to anemia?
Any disruption in the synthesis of heme or globin will result in decreased hemoglobin synthesis, leading to anemia. Both iron and protoporphyrin IX are required for heme synthesis, and the proper synthesis of globin chains is necessary for the formation of the globin part of hemoglobin.
Anemia of abnormal iron metabolism vs. Hemoglobinopathies. How are both caused differently?
If Fe is ⬇️ or Protoportphyrin IX is ⬇️ → ⬇️ Heme → ⬇️ Hemoglobin → Anemia of Abnormal Iron Metabolism
If there is a ⬇️ in polypeptide chains →⬇️ globin →⬇️ Hemoglobin = Hemoglobinopathies
What are the main causes of anemia of abnormal iron metabolism?
1) Deficiency of the raw material iron, which is seen in iron deficiency anemia. (Most common)
2) Defective release of stored iron from macrophages, as observed in anemia of chronic disorders (ACD).(2nd most common/most common in hospitals)
3) Failure to incorporate iron into heme, seen in sideroblastic anemias. Sideroblastic anemias are characterized by the inability of the body to properly utilize iron for heme synthesis.
What are some examples of chronic diseases associated with anemia of chronic disorders?
Infectious: Tuberculosis, Pulmonary infections (pneumonia), Chronic UTI, Meningitis…
Non Infectious: Rheumatic Fever, Rheumatoid Arthritis, Thermal Injury, Myocardial Infarction, Severe trauma…
Malignant: Carcinoma, Hodgkin’s Disease, Multiple Myeloma, Leukemia…
What are the typical presenting symptoms and physical findings in a patient with anemia of chronic disorders (ACD)?
The presenting symptoms and physical findings in a patient with anemia of chronic disorders are usually those related to the primary infection, inflammation, or malignancy causing the anemia.
How is the severity of anemia in anemia of chronic disorders (ACD) usually described?
The severity of anemia in ACD is generally mild to moderate. The hemoglobin (Hb) level is typically around 1-2 g/dL below the patient’s normal baseline. The hematocrit (Hct) is usually mildly decreased, ranging from 28% to 40%, but it can be even lower in some cases.
What are the typical laboratory findings in anemia of chronic disorders?
ABC:
The MCV, MCH, & MCHC are generally normal, although the MCV and MCHC may be decreased.
RDW is normal
ESR is elevated
The RBC morphology typically shows normocytic and normochromic cells, but they may also be normocytic and hypochromic or, less commonly, microcytic and hypochromic.
Slight anisocytosis and poikilocytosis (abnormal cell shape) may be observed, but they are usually less prominent than in iron deficiency anemia. Target cells may be present.
What is the reticulocyte count like in anemia of chronic disorders?
The reticulocyte count in anemia of chronic disorders is usually normal or even decreased. This reflects the hypoproliferative nature of this type of anemia, indicating reduced red blood cell production.
What are the characteristic findings in the bone marrow of a patient with anemia of chronic disorders?
1) Lack of erythroid hyperplasia: The bone marrow does not show the expected increase in erythroid cells, which normally occurs as a compensatory mechanism in anemia.
2) Presence of stored iron in macrophages: Staining of bone marrow samples with Perl’s Prussian Blue confirms the increased presence of stored iron in macrophages.
3) Decreased number of sideroblasts: Sideroblasts, which are nucleated red blood cells with iron granules, are decreased in number compared to the normal range. Normally, sideroblasts constitute 20%-50% of the nucleated red blood cells in the bone marrow.
What are the characteristic findings in iron studies for a patient with anemia of chronic disorders (ACD)?
1) Low serum iron level (hypoferremia): Similar to iron deficiency, the serum iron level is low in ACD.
2) Low total iron-binding capacity (TIBC): In contrast to iron deficiency, the TIBC is low in ACD.
3) Low percentage of transferrin saturation: This finding is shared with iron deficiency anemia, but in ACD, it is usually greater than 16%.
4) Elevated serum ferritin levels (CHARACTERISTIC): In contrast to the low levels typically seen in iron deficiency anemia, the elevated serum ferritin levels reflects the presence of normal to increased storage iron in ACD.
5) Increased concentration of certain plasma proteins: There is an elevation in the concentration of specific plasma proteins, such as fibrinogen, haptoglobin, and C-reactive protein (CRP), in ACD. (Positive acute phase reactants)
6) Decreased levels of albumin and transferrin (negative acute phase reactants)
What are the major factors that cause hypoferremia in ACD?
The increase in hepcidin and lactoferrin
What are the proposed mechanisms involved in the pathogenesis of anemia of chronic disorders (ACD)?
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Hypoferremia:
a. Decreased iron release from storage in macrophages: Activated macrophages or monocytes release cytokines, such as hepcidin, which inhibits the mobilization of iron from the stores.
b. Increased lactoferrin production: Lactoferrin, an iron-binding protein released from neutrophils during acute inflammation, may contribute to hypoferremia with normal iron stores in ACD. Lactoferrin can remove iron bound to transferrin and transfer it back to macrophages.
c. Decreased iron absorption: Hepcidin released by the liver decreases iron absorption from the intestines, further contributing to hypoferremia. - Shortened erythrocyte survival: Erythrocytes in ACD have a shortened lifespan of approximately 90 days, leading to increased red blood cell destruction.
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Failure of the bone marrow:
a. Inadequate compensatory erythropoiesis: Despite the increased demand for erythrocytes due to anemia or shortened red cell lifespan, the bone marrow fails to increase erythropoiesis to compensate for the loss. This can be attributed to reduced erythropoietin levels (as expected in anemia) and a depressed bone marrow response to erythropoietin.
b. Inhibition of erythropoiesis by cytokines: Various cytokines released during chronic inflammation can inhibit erythropoiesis, further contributing to the failure of the bone marrow to produce an adequate number of erythrocytes.
What is the key diagnostic feature of ACD?
The key diagnostic feature is hypoferremia (low serum iron) with adequate or increased reticuloendothelial (RE) iron stores.
How is ACD treated?
In most cases, ACD is mild, and treatment of the anemia itself is not necessary. The primary focus of therapy is directed towards treating the underlying disease. Successful treatment of the underlying condition is essential for correcting the anemia in ACD.
How does ACD respond to iron therapy?
It is important to note that ACD does not typically respond to iron therapy despite the low serum iron levels.
