NORMAL STRUCTURE & FUNCTION
Blood is an extremely complex fluid, composed of both formed elements (red cells, white cells, platelets) and plasma. Red blood cells (erythrocytes) are the most common formed elements, carrying oxygen to the cells of the body via their main component, hemoglobin. White blood cells are generally present at about 1/700th the number of erythrocytes and function as mediators of immune responses to infection or other stimuli of inflammation. Platelets are the formed elements that participate in coagulation. Plasma is largely water, electrolytes, and plasma proteins. The plasma proteins most important in blood clotting are the coagulation factors. Because blood circulates throughout the body, alterations in normal blood physiology—either formed elements or plasma proteins—may have widespread adverse consequences.
A. Bone Marrow and Hematopoiesis
Although the mature formed elements of blood are quite different from each other in both structure and function, all of these cells develop from a common hematopoietic stem cell population, which resides in the bone marrow. The developmental process is called hematopoiesis and represents an enormous metabolic task for the body. More than 100 billion cells are produced every day. This makes the bone marrow one of the most active organs in the body. In adults, most of the active marrow resides in the vertebrae, sternum, and ribs. In children, the marrow is more active in the long bones.
The process of differentiation from stem cell to mature erythrocyte, granulocyte, lymphocyte, monocyte, or platelet is shown in Figure 6–1. It is not clear exactly what early events lead dividing stem cells down a particular path of development, but many different peptides, called cytokines, are clearly involved (Table 6–1; see also Chapter 3). Perhaps because mature white blood cells have a much shorter half-life in the circulation, white blood cell precursors usually outnumber red blood cell precursors by a ratio of 3:1 in the bone marrow.
Hematopoiesis: development of the formed elements of blood from bone marrow stem cells. Cells below the horizontal line are found in normal peripheral blood. The principal cytokines that stimulate each cell lineage to differentiate are shown. (CSF, colony-stimulating factor; EPO, erythropoietin; G, granulocyte; IL, interleukin; M, macrophage; SCF, stem cell factor; TPO, thrombopoietin) See Table 6–1 for details. (Redrawn, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005.)
TABLE 6–1Cytokines that regulate hematopoiesis. ||Download (.pdf) TABLE 6–1 Cytokines that regulate hematopoiesis.
|Cytokine ||Cell Lines Stimulated ||Cytokine Source |
|IL-1 || |
|Multiple cell types |
|IL-3 || |
|T lymphocytes |
|IL-4 ||Basophil ||T lymphocytes |
|IL-5 ||Eosinophil ||T lymphocytes |
|IL-6 || |