The oxygen required by tissues for aerobic metabolism is supplied by the circulating mass of mature erythrocytes (red blood cells). The circulating red blood cell population is continually renewed by the erythroid precursor cells in the marrow, under the control of both humoral and cellular growth factors. This cycle of normal erythropoiesis is a carefully regulated process. Oxygen sensors within the kidney detect minute changes in the amount of oxygen available to tissue and by releasing erythropoietin are able to adjust erythropoiesis to match tissue requirements. Thus, normal erythropoiesis is best described according to its major components, including red blood cell structure, function, and turnover; the capacity of the erythroid marrow to produce new red blood cells; and growth factor regulation.
STRUCTURE OF THE RED BLOOD CELL
The mature red blood cell is easily recognized because of its unique morphology (Figure 1-1). At rest, the red blood cell takes the shape of a biconcave disc with a mean diameter of 8 μm, a thickness of 2 μm, and a volume of 90 fL. It lacks a nucleus or mitochondria, and 33% of its contents is made up of a single protein, hemoglobin. Intracellular energy requirements are largely supplied by glucose metabolism, which is targeted at maintaining hemoglobin in a soluble, reduced state, providing appropriate amounts of 2,3-diphosphoglycerate (2,3-DPG), and generating adenosine triphosphate (ATP) to support membrane function. Without a nucleus or protein metabolic pathway, the cell has a limited lifespan of 100–120 days. However, the unique structure of the adult red blood cell is perfect for its function, providing maximum flexibility as the cell travels through the microvasculature (Figure 1-2).
Red blood cell morphology. On the stained blood smear, red blood cells appear as a relatively uniform population of anucleate, biconcave cells with a diameter of approximately 8 μm and a width of 2 μm.
Red blood cell shape and pliability. A: On scanning EM, the biconcave shape of the red cell at rest is readily apparent. B: The exceptional pliability of circulating red cells is shown in this section of a small blood vessel.
A. Inner and Outer Layers
The shape, pliability, and resiliency of the red blood cell are largely determined by its membrane. The structure of this membrane is illustrated in Figure 1-3. It is a lipid sheath, just two molecules thick, consisting of closely packed phospholipid molecules. The various surface lipids are in constant motion, forming microdomains or "rafts," which play important physiologic roles. The external surface of the membrane is rich in phosphatidylcholine, sphingomyelin, and glycolipid, whereas the inner layer is largely phosphatidylserine, phosphatidylethanolamine, ...