Anemia Anemia is defined clinically as a decrease in the concentration of hemoglobin in the blood for the age and sex of an individual. Although in certain anemias this decreased concentration of hemoglobin is caused by a decrease in the amount of hemoglobin in each cell, most anemias are caused by a reduction in the number of erythrocytes. Causes of anemia include loss of blood (hemorrhage), insufficient production of erythrocytes, or accelerated destruction of erythrocytes in the circulation. Insufficient dietary iron or deficiencies of vitamins such as vitamin B12 or folic acid can lead to decreased production of erythrocytes. Gastric atrophy, as a result of autoimmune disease, with concomitant destruction of the parietal cells that secrete intrinsic factor, a molecule essential for absorption of vitamin B12 by cells in the ileum, is the cause of a form of anemia called pernicious anemia. The clinical symptoms of anemia vary, depending on the type of anemia, the underlying cause, and other associated medical conditions. The common symptoms of even mild anemia include weakness, fatigue, and loss of energy. The other symptoms associated with anemia are shortness of breath, frequent headaches, difficulty concentrating, mental confusion, loss of sexual drive, dizziness, leg cramps, insomnia, and pale skin.
interaction, which slows the neutrophil and causes it to roll on the surface of the endothelium. In the second phase, another group of adhesion molecules on the neutrophil surface, called integrins (VLA-5), are activated by chemokine signals from the endothelial cells. In the third phase, integrins and other adhesion molecules from the immunoglobulin superfamily (e.g., intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) expressed on the neutrophil surface engage with their specific receptors on the endothelial cells,
Sickle Cell Disease Sickle cell disease is caused by a single-point mutation in the gene that encodes the -globin chain of hemoglobin A. The result of this mutation is an abnormal  -globin chain in which the amino acid valine is substituted for glutamic acid in position 6. Hemoglobin containing this abnormal  -globin chain is designated sickle hemoglobin (HbS). The substitution of the hydrophobic valine for the hydrophilic glutamic acid causes HbS to aggregate under conditions of reduced oxygen tension. Instead of the normal biconcave disc shape, many of the erythrocytes become sickle-shaped at low oxygen tension, hence the name of this disease (Fig. F10.3.1). Sickled erythrocytes are more rigid than normal cells and adhere more readily to the endothelial surface. Thus, sickled erythrocytes may pile up in the smallest capillaries, depriving portions of tissues and organs of oxygen and nutrients. Large-vessel obstruction may also occur, which in children frequently leads to stroke. Sickled erythrocytes are also more fragile and break down or are destroyed more quickly (after 20 days) than normal erythrocytes.
Sickle cell disease is a homozygous recessive genetic disorder. However, heterozygous individuals with sickled cell trait may occasionally have clinical consequences at high altitude or when under extreme physical stress.
FIGURE F10.3.1 • Photomicrograph of a sickle cell anemia blood smear. Blood smear stained with Wright’s stain shows abnormal “boat”and “sickle”-shaped cells from an individual with sickle cell anemia. 400.