Hematology: A Pathophysiologic Approach

Leukemia and related disorders

Introduction The term leukemia refers to a family of malignant neoplasms of the bone marrow characterized by clonal proliferation of hematopoietic cells and often accompanied by circulating immature cells in the peripheral blood. Leukemia is often accompanied by suppression of…

Genetic basis of hematologic neoplasia

Key points The cell cycle is controlled at two steps, the G1 and G2 restriction points, by cyclin-dependent protein kinases (CDKs). CDKs are subject to control by cyclin proteins, cyclin-CDK inhibitors such as cell damage-sensing protein (p53) and retinoblastoma (RB)…

Immune system and related disorders

Key points Immune system organs include the bone marrow, thymus, lymph nodes, spleen, tonsils, as well as gut-, skin-, and bronchial-associated lymphoid tissues. The major types of immune system cells are lymphocytes, plasma cells, and antigen-presenting cells (APCs). The four…

Myeloid cells

Key points Under the influence of specific cytokines, common myeloid progenitors in the marrow undergo differentiation into granulocytes (neutrophils, eosinophils, mast cells, basophils, and monocytes. Neutrophils are phagocytic microbicidal cells that contain cytoplasmic granules rich in proteolytic enzymes. In response…

Megaloblastic anemia

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Aplastic anemia and related disorders

Key points Aplastic anemia is broadly defined as pancytopenia (low hemoglobin, leukocyte count, and platelet count) with a hypocellular bone marrow. Some inherited forms of aplastic anemia present in early childhood and may be associated with increased risk for development…

Hemolytic anemia

Key points Hemolytic anemia can be caused by intrinsic red blood cell (RBC) defects (hemoglobin defects, enzyme defects, or membrane defects) or extrinsic causes (autoimmune, vascular defects, toxins, or heat). Intravascular hemolysis results from direct destruction of circulating s by…

Red blood cell metabolism and enzyme defects

Key points Red blood cell (RBC) energy is supplied entirely by anerobic glycolysis. Three auxiliary metabolic pathways branch from the glycolytic pathway: the hexose monophosphate (HMP) shunt, the 2,3-bisphosphoglycerate (2,3-BPG) pathway, and the methemoglobin reductase pathway. The HMP shunt produces…

Hemoglobinopathy

Key points Normal adult hemoglobins include hemoglobins A (97%), A 2 ( 2%–3%), and F (<1%). Trace quantities of nonfunctional hemoglobins (methemoglobin, carboxyhemoglobin, sulfhemoglobin, and nitrosohemoglobin) are present in normal blood. Specific inherited point mutations of the beta-globin gene lead…

Iron, heme, and hemoglobin

Key points Dietary iron is absorbed by duodenal enterocytes, transported in the blood bound to the iron carrier protein transferrin, and released to transferrin receptor-bearing hepatocytes and macrophages. Hereditary hemochromatosis is an iron-overload condition often caused by high iron (Fe)…