Key Points

• Stem cells have self-renewal capability and differentiate into red blood cells, granulocytes, monocytes, lymphocytes, and platelets.

• Red cell production is controlled by erythropoietin and white cell production by granulocyte colony-stimulating factor.

Blood cell production normally takes place in the bone marrow, and all the circulating cellular elements of the blood arise from the level of a pluripotent hematopoietic stem cell (Fig. 39-1). Hematopoietic stem cells have two important properties, extensive self-renewal and ability to differentiate and mature into red blood cells, granulocytes

Figure 39-1 Common cellular elements seen in bone marrow aspirate, including plasma cell, polymorphonuclear neutrophil and band, eosinophil, and nucleated red blood cell. (From the American Society of Hematology image Bank image #505. Copyright 1996 American Society of Hematology, used with permission.)

(neutrophils, eosinophils, basophils), monocytes, platelets, and lymphocytes (T cells, B cells, and NK cells). Little is known about the molecular mechanisms that control self-renewal, but this ability of stem cells is critical to the success of treatments such as bone marrow transplantation. More is known about the factors that control hematopoietic differentiation and maturation.

Hematopoietic stem cells are rare in number, estimated at approximately 1 in 1 x 106 bone marrow cells, or 0.05% of all marrow cells. The fact that they exist at all is best defined by their ability to support bone marrow regrowth after stem cell transplantation or marrow recovery after severe marrow suppression from chemotherapy or radiation. Two major lineages arise from the pluripotent hematopoietic stem cell: the common myeloid progenitor cell and the common lymphoid progenitor cell. Lymphopoiesis then proceeds to the differentiation of T cells, B cells, natural killer (NK) cells, and some dendritic cells. The common myeloid progenitor gives rise to red cells, granulocytes of all types, monocytes and macrophages (and some dendritic cells), and platelets.

The regulation of the terminal stages of hematopoietic differentiation and maturation is under the control of a variety of hormones and cytokines. Red cell production is under the control of erythropoietin (EPO), a glycoprotein hormone secreted by the kidney in response to hypoxia or anemia. Neutrophil production is under the control of granulocyte colony-stimulating factor (G-CSF). Eosinophil production is under the control of interleukin-5 (IL-5). Monocyte and macrophage production is under the control of macrophage colony-stimulating factor (M-CSF) and, to a lesser extent, granulocyte-macrophage colony-stimulating factor (GM-CSF). Platelet production is under the control of thrombo-poietin (TPO), produced in the liver. TPO also stimulates proliferation and release of hematopoietic stem cells. Of these various growth factors, EPO and G-CSF have important uses clinically; TPO is under clinical development. The number of cellular elements in the blood is tightly controlled by these regulatory hormones. Table 39-1 shows the normal ranges for the various cellular elements of the blood in adults.

Table 39-1 Cellular Elements of the Blood (Adult)

Red Blood Cells (RBCs)

Men

Women

Hematocrit (%)

46.0 ±4.0

40.0 ±4.0

Hemoglobin (g/dL)

15.7 ±1.7

13.8 ±1.5

RBC count (x106/^L)

5.3 ±0.7

4.6 ±0.5

Reticulocytes (%)

1.6 ±0.5

1.4 ±0.5

Mean corpuscular volume (fl)

88.0 ±8.0

Mean cell hemoglobin (pg/RBC)

30.4 ±2.8

Mean cell hemoglobin concentration (g/dL of RBC)

34.4 ±1.1

Red cell volume distribution width (RDW) (%)

13.1 ±1.4

Platelets (/^L)

150,000-300,000

White Blood Cells

Range (/^L)

Range(%)

All white blood cells

4300-10,000

100

Total neutrophils

2000-7000

20-70

Segmented neutrophils

1500-6000

15-60

Band neutrophils

500-1000

5-10

Lymphocytes

1500-4000

15-40

Monocytes

100-900

1-9

Eosinophils

100-700

1-7

Basophils

0-150

0-1.5

Disorders of Red Blood Cells

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