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.
Describe the pathogenesis of the anemia of renal failure.
Understand the clinical applications, efficacy, and safety of recombinant erythropoietin therapy.
All of the different types of anemia covered in the preceding chapters (Chapters 4,5,6) and those that follow (Chapters 8,,9,10,11) are primary hematologic disorders resulting from inherited or acquired defects that directly lower the red cell mass by impairing red cell production (erythropoiesis) or shortening red cell survival. The importance of these disorders notwithstanding, it is worth stressing that some of the most common forms of anemia, including those that are most prevalent in hospitalized patients, occur secondary to an underlying chronic illness (see box titled “Anemia of Chronic Illness”). It is these secondary anemias that are the focus of this chapter.
ANEMIA OF CHRONIC INFLAMMATION
A chronic systemic inflammatory disorder persisting for more than a month is nearly always accompanied by anemia. 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 acquired immunodeficiency syndrome (AIDS), the human immunodeficiency virus (HIV) virus can directly infect hematopoietic progenitor cells, whereas in malaria and babesiosis, the parasite infects and destroys circulating red cells.
Anemia of Chronic Illness
Anemia of chronic inflammation
Connective tissue disorders
Anemia of renal insufficiency
Anemia of chronic liver disease
Anemia of endocrine hypofunction
Tumors may trigger an inflammatory response in a variety of ways. Some secrete inflammatory cytokines, as part of either their normal profile of gene expression (e.g., in tumors of immune cells, such as T-cell lymphomas) or an abnormal gene expression profile that is acquired during the process of transformation (e.g., certain solid tumors such as carcinomas or sarcomas). In other tumors, impaired oxygen or nutrient supply to the interior of the tumor results in necrosis, releasing a number of factors that elicit an inflammatory response, whereas other tumors damage tissue as they invade, eliciting host responses similar to those seen during wound healing. If tumors primarily or secondarily involve the 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 ...