Hematopoiesis begins by 3 weeks of gestation with erythropoiesis in the yolk sac. By 2 months’ gestation, the primary site of hematopoiesis migrates to the liver. By 5 to 6 months’ gestation, the process shifts from the liver to the bone marrow. An extremely premature infant may have significant extramedullary hematopoiesis due to limited bone marrow hematopoiesis. During infancy, virtually all marrow cavities are actively hematopoietic and the proportion of hematopoietic to stromal elements is quite high. As the child grows, hematopoiesis moves to the central bones of the body (vertebrae, sternum, ribs, and pelvis), and the marrow is gradually replaced with fat. Hemolysis or marrow damage may lead to marrow repopulation of cavities where hematopoiesis previously had ceased or may delay the shift of hematopoiesis. Hepatosplenomegaly in patients with chronic hemolysis may signify extramedullary hematopoiesis. When a patient with cytopenia is being evaluated, a bone marrow examination provides valuable information about processes that lead to underproduction of circulating cells. In addition, bone marrow infiltration by neoplastic elements or storage cells often occurs in concert with infiltration in the spleen, liver, and lymph nodes.
The hematopoietic cells consist of the following: 1.
Small compartment of pluripotential progenitor stem cells that resemble small lymphocytes and are capable of forming all myeloid elements 2.
Large compartment of committed, proliferating cells of myeloid, erythroid, and megakaryocytic lineage 3.
Large compartment of postmitotic maturing cells(Fig. 149-1)
The bone marrow is the major storage organ for mature neutrophils and contains about seven times the intravascular pool of neutrophils. It contains 2.5 to 5 times as many cells of myeloid lineage as cells of erythroid lineage. Smaller numbers of megakaryocytes, plasma cells, histiocytes, lymphocytes, and stromal cells are also stored in the marrow.
Erythropoiesis (red blood cell [RBC] production) iscontrolled by erythropoietin, a glycoprotein that stimulatesprimitive pluripotential stem cells to differentiate along the
Figure 149-1 Major cytokine sources and actions to promote hematopoiesis. Cells of the bone marrow microenvironment, such as macrophages, endothelial cells, and reticular fibroblasts, produce macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) after stimulation. For all lineages, optimal development requires a combination of early and late acting factors. BFU, Burst-forming unit; CFU, colony-forming unit; EPO, erythropoietin; IL, interleukin; MSC, myeloid stem cell; PSC, pluripotent stem cell; TNF, tumor necrosis factor; TPO, thrombopoietin. (From Sieff CA, Nathan DG, Clark SC: The anatomy and physiology of hematopoiesis. In Orkin SH, Nathan DG, editors: Hematology of Infancy and Childhood, ed 5, Philadelphia, 1998, WB Saunders, p 168.)
Table 149-1 Presentation of Hematologic Disorders CONDITION SYMPTOMS AND SIGNS COMMON EXAMPLES Anemia Pallor, fatigue, heart failure, jaundice Iron deficiency, hemolytic anemia Polycythemia Irritability, cyanosis, seizures, jaundice, stroke, headache Cyanotic heart disease, infant of diabetic mother, cystic fibrosis