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PRINCIPLES OF TOXICOLOGY

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TABLE 4.2 Leukemias and Lymphomas<br />

4.3 THE MYELOID SERIES: ERYTHROCYTES, PLATELETS, GRANULOCYTES<br />

(NEUTROPHILS), MACROPHAGES, EOSINOPHILS, AND BASOPHILS<br />

Red Blood Cells (RBC): Erythrocytes<br />

4.3 THE MYELOID SERIES 91<br />

ICD No. General Description<br />

ICD 200: lymphosarcoma and reticulosarcoma Lymphocytic lymphomas involving resident<br />

lymphocytes in various tissues such as the liver,<br />

spleen, lung, skin, bone marrow, and gastrointestinal<br />

tract<br />

ICD 201: Hodgkin’s disease Lymph node cancers exhibiting Reed–Sternberg cells<br />

ICD 202: other malignant neoplasms of lymphoid and Involves resident macrophage cell types located in the<br />

histiocytic tissue<br />

peripheral tissues such as lymph nodes, spleen, skin,<br />

liver, and connective tissue<br />

ICD 203: multiple myeloma Cancer of a specific plasma cell (antibody producing B<br />

lymphocyte)<br />

ICD 204: lymphoid leukemia Cancer of circulating B and T lymphocytes<br />

ICD 205: myeloid leukemia Cancer of the myeloid series, usually granulocytes<br />

(neutrophils or PMNs)<br />

ICD 206: monocytic leukemia Cancers of the monocytic series involving the bone<br />

marrow–derived monoblast<br />

ICD 207: erythroleukemia Cancer of RBC precursors<br />

ICD 208: leukemia not otherwise specified<br />

Source: International Classification of Disease (ICD), 9th ed.<br />

During erythrocyte maturation, the blast forming unit-erythrocyte or BFU-E matures into the colony<br />

forming unit-erythrocyte (CFU-E), which finally evolves into a mature erythrocyte after extrusion of<br />

the nucleus and acquisition of hemoglobin and a mature cytoskeletal support system. Accelerated<br />

erythrocyte formation due to anemia, may result in the release of RBCs prior to the loss of the nucleus.<br />

These immature erythrocytes known as reticulocytes can be found circulating in the blood in increased<br />

numbers (i.e., reticulocytosis). Physicians may suspect anemia or a bleeding disorder if the number of<br />

reticulocytes exceeds their normal blood level (normal circulating reticulocyte levels are 5 percent of<br />

the total number of RBCs) or if other clinical parameters are abnormal, specifically, the number of<br />

RBCs, the percent volume of packed RBCs or the hemoglobin content. Once the red blood cell is<br />

released into circulation, it has a normal lifespan of 120 days. Damaged or senescent RBCs are<br />

sequestered in the spleen and destroyed by splenic macrophages.<br />

Mature RBCs are discoid-shaped and devoid of a nucleus and mitochondria. They are rich in the<br />

heme-containing protein, hemoglobin, which transports oxygen to peripheral tissues and carries carbon<br />

dioxide from the periphery to the lungs, where it is exhaled. Erythrocytes also provide a pH buffering<br />

function by converting carbon dioxide to carbonic acid via the enzymatic activity of carbonic<br />

anhydrase. Erythrocytes possess an outer membrane supported by a complex cytoskeletal system of<br />

various proteins that are essential for carrying out the normal functions of the RBC. Erythrocytes<br />

normally constitute around 40 percent by volume of whole blood and number around 3,500,000–<br />

5,000,000 per cubic millimeter. The normal hemoglobin content of 100 mL of blood is 14 g. When<br />

the 120-day lifespan of erythrocytes is shortened to the extent that stimulated erythrocyte replacement<br />

cannot keep pace, varying degrees of anemia may result.<br />

There are numerous causes of anemia, including abnormal hemoglobin inherited in the form of<br />

sickle cell anemia or thalassemia; congenital nonspherocytic anemias involving defects in biochemical<br />

pathways in the RBC (e.g., glucose-6-phosphate dehydrogenase deficiency); congenital spherocytosis,

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