Anemias Associated With Chronic Illness



INTRODUCTION





LEARNING OBJECTIVES


After studying this chapter you should be able to:




  • Name the categories of chronic illnesses that are associated with anemia.



  • Explain the pathogenesis of the anemia of chronic inflammation and the role of hepcidin.



  • Understand the pathogenesis of the anemia of renal failure.



  • Summarize the use of recombinant erythropoietin: its efficacy, safety, and clinical applications.




All of the different types of anemia covered in preceding chapters (4-6) as well as those that follow this one (Chapters 8-11) are primary hematologic disorders arising because of an inherited or an acquired defect that directly lowers the red cell mass by impairing erythropoiesis or shortening cell survival. The importance of these -disorders notwithstanding, it is worth stressing that among the most common anemias and the ones most prevalent in patients hospitalized on a medical or pediatric service are those secondary to an underlying chronic illness (summarized in Table 7-1).






ANEMIA OF CHRONIC INFLAMMATION





A chronic systemic inflammatory disorder persisting more than a month is nearly always accompanied by anemia. As indicated in Table 7-1, the chronic inflammation is usually due to infection, tumor, or a connective tissue disorder. A wide array of infections may be responsible, including subacute bacterial endocarditis, tuberculosis, lung abscess, osteomyelitis, and pyelonephritis. In some types of chronic infections, the pathogenesis is more complex. For example, in AIDS the HIV virus can directly infect hematopoietic progenitor cells. In malaria and babesiosis, the parasite infects and destroys circulating red cells.




TABLE 7-1   Anemia of Chronic Illness 



Tumors vary considerably in their ability to trigger an inflammatory response. Some secrete inflammatory cytokines as part of their profiles of aberrant gene expression. In others, impairment of oxygen or nutrient supply to the interior of the tumor can result in necrosis and an inflammatory response. In some tumors, such as the leukemias and lymphomas and those that have metastasized to bone, red cell production is further compromised by marrow invasion.



Anemia is encountered in a wide variety of inflammatory disorders not associated with either infection or cancer. In many of these conditions, autoimmune attack on the patient’s cells and tissues is accompanied by a robust inflammatory response. Rheumatoid arthritis is the most prevalent connective tissue disorder and a prototypical cause of anemia of chronic inflammation. Polymyalgia rheumatica/temporal arteritis is associated with even more intense inflammation and accordingly more severe anemia. In anemia due to systemic lupus erythematosus, the deleterious impact of inflammation is often compounded by increased red cell destruction (due to the presence of autoantibodies) and the anemia of renal insufficiency (described in the following section).



PATHOGENESIS AND LABORATORY FINDINGS



It has been long appreciated that the anemia of chronic inflammation is associated with a systemic derangement of iron homeostasis. Increased amounts of iron are stored in macrophages in the bone marrow, liver, and spleen, as reflected by elevated levels of ferritin in serum (Chapter 5, Fig. 5-5B). However, there is a block in the transfer of this excess iron to the plasma, resulting in low levels of serum iron (Chapter 5, Fig. 5-5A). For unclear reasons, the level of total transferrin in the serum is also low. Because of this limitation in iron availability, erythropoiesis is somewhat “iron deficient.” Erythroid precursors in the bone marrow have decreased amounts of cytoplasmic iron, and the red cells that enter the circulation are slightly smaller than normal. The suppression of red cell production results in a low reticulocyte index. Because this block in iron utilization is subtle, the degree of anemia in patients with chronic inflammation is rarely severe. If a patient with one of the disorders listed previously has a hemoglobin level of less than 8 g/dL, it is essential to look for additional contributors such as bleeding or hemolysis.



In the last 5 years, the pathogenesis of the anemia of chronic inflammation has been greatly clarified by the realization that plasma hepcidin levels are markedly increased, as a direct result of induction of transcription by inflammatory cytokines. As shown in Figure 7-1, hepcidin blocks both iron absorption from the gut and the egress of iron from macrophages, thus explaining both increased storage iron and reduced levels of serum iron.

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Jun 12, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Anemias Associated With Chronic Illness
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