Autosomaldominantdisordercausedbymutationsthataffecttheredcellmembraneskeleton,leadingtolossofmembraneandeventualconversionofredcellstospherocytes,whicharephagocytosedandremovedinthespleen
Manifestedbyanemia,splenomegaly
Blockageofvesselsbysickledcellscausespaincrisesandtissueinfarction,particularlyofthemarrowandspleen •Autosomalcodominantdisorderscausedbymutationsinαorβ-globinthatreducehemoglobinsynthesis,resultinginamicrocytic,hypochromicanemia.Inβ-thalassemia,unpairedα-globinchainsformaggregatesthatdamageredcellprecursorsandfurtherimpairerythropoiesis.
•X-linkeddisordercausedbymutationsthatdestabilizeG6PD,makingredcellssusceptibletooxidantdamage
Anemias of diminished erythropoiesis include those caused by an inadequate dietary supply of nutrients, particularly iron, folic acid, and vitamin B12. Other anemias of this type are associated with bone marrow failure (aplastic anemia), systemic inflammation (anemia of chronic inflammation), or bone marrow infiltration by tumor or inflammatory cells (myelophthisic anemia). In this section, some common examples of anemias of these types are discussed individually.
Deficiency of iron is the most common nutritional deficiency in the world and results in clinical signs and symptoms that are mostly related to anemia. About 10% of people living in developed countries and 25% to 50% of those in developing countries are anemic, and in both settings the most frequent cause is iron deficiency. The factors responsible for iron deficiency differ in various populations and are best understood in the context of normal iron metabolism.
The normal total body iron mass is about 2.5 g for women and 3.5 g for men. Approximately 80% of functional body iron is present in hemoglobin, with the remainder located in myoglobin and iron-containing enzymes (e.g., catalase, cytochromes). The iron storage pool, consisting of hemosiderin and ferritin-bound iron in the liver, spleen, bone marrow, and skeletal muscle, contains on average 15% to 20% of total body iron. Because serum ferritin is largely derived from this storage pool, the serum ferritin level is a good measure of iron stores. Assessment of bone marrow iron is another reliable but more invasive method for estimating iron stores. Iron is transported in the plasma bound to the protein transferrin. In normal persons, transferrin is about 33% saturated with iron, yielding serum iron levels that average 120 µg/dL in men and 100 µg/dL in women. Thus, the normal total iron-binding capacity of serum is 300 to 350 µg/dL.
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In keeping with the high prevalence of iron deficiency, evolutionary pressures have yielded metabolic pathways that are strongly biased toward iron retention. Iron is lost at a rate of 1 to 2 mg/day through the shedding of mucosal and skin epithelial cells, and this loss must be balanced by the absorption of dietary iron, which is tightly regulated (described later). The normal daily Western diet contains 10 to 20 mg of iron. Most is found in heme within meat and poultry, with the remainder present as inorganic iron in vegetables. About 20% of heme and 1% to 2% of nonheme iron are absorbable; hence, the average Western diet contains sufficient iron to balance fixed daily losses.
Regulation of iron absorption occurs within the duodenum (
Fig. 12.9 ). After reduction by ferric reductase, ferrous