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Anemias are characterized by a decrease and polycythemias by an increase of the red cell mass. Because the anemias have their principal effect by decreasing the oxygen-carrying capacity of blood, they are best expressed in terms of hemoglobin concentration. Anemia may cause symptoms because of tissue hypoxia (e.g., fatigue, dyspnea on exertion). These manifestations are also caused by compensatory attempts to ameliorate hypoxia (e.g., hyperventilation, tachycardia, and increased cardiac output). Tissue hypoxia sensing is ubiquitous and it is signaled by an increased level of transcription factors, hypoxia-inducible transcription factors HIF-1 and HIF-2. HIFs upregulate transcription of many genes that are involved in angiogenesis, energy metabolism, and iron balance, as well as erythropoiesis, including the principal erythropoietic factor, erythropoietin. The classification of anemia is evolving, as it should take into account new kinetic and molecular findings.

The polycythemias (erythrocytoses) are best expressed in terms of the packed red cell volume (hematocrit), as their clinical manifestations are primarily related to the expanded red cell mass and resulting increased viscosity of blood, and specific features related to the pathophysiology stemming from the molecular causative defect (e.g., thrombosis in polycythemia vera, cyanosis in congenital methemoglobinemia). The polycythemias are either caused by an aberrant function of hematopoietic progenitors—primary polycythemias (e.g., a monoclonal expansion of a multipotential hematopoietic cell [polycythemia vera] or gain-of-function mutations of erythroid progenitors)—or are caused by increased levels of circulating erythropoiesis-stimulating factors, usually erythropoietin—secondary polycythemias (e.g., chronic pulmonary disease, cobalt poisoning or high oxygen affinity hemoglobin mutants). Some polycythemias have hypersensitive erythroid progenitors as well as increased levels of erythropoietin, and thus share features of both primary and secondary polycythemia; that is, Chuvash polycythemia. Persons with relative (spurious) polycythemia have a contracted plasma volume and normal red cell mass.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: HIF, hypoxia-inducible factor.

Pathophysiology and Manifestations

Effect on Oxygen Transport

The clinical manifestations of anemia are a function of the degree of tissue hypoxia and the etiology and pathogenesis of the specific anemia (e.g., splenomegaly characteristic of hereditary spherocytosis, neurologic degeneration, or gastric atrophy of pernicious anemia). Decreased oxygen-carrying capacity mobilizes compensatory mechanisms designed to prevent or ameliorate tissue anoxia. The red cells also carry carbon dioxide from the tissues to the lungs and help distribute nitric oxide throughout the body (see Chap. 49), but transport of these gases does not appear to be dependent on the number of red cells available and remains normal in anemic patients. Tissue hypoxia occurs when the pressure of oxygen in the capillaries is too low to provide cells with enough oxygen for the cells’ metabolic needs. In an average person, the red cell mass must provide the total body tissues with approximately 250 mL/min of oxygen to support life. Because the oxygen-carrying capacity of normal blood is 1.34 mL per gram of hemoglobin (approximately 200 mL per liter of ...

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