Porth's Essentials of Pathophysiology, 4e

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Disorders of White Blood Cells and Lymphoid Tissues

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Many cytokines derived from lymphocytes or bone marrow stromal cells stimulate the growth and produc- tion of new blood cells. Several members of this family are called colony-stimulating factors (CSFs) because of their ability to promote the growth of hematopoi- etic cell colonies in the laboratory. The CSFs that act on committed progenitor cells include erythropoietin (EPO); thrombopoietin (TPO); granulocyte-monocyte colony-stimulating factor (GM-CSF), which stimulates progenitors for granulocytes, monocytes, erythrocytes, and megakaryocytes; granulocyte colony-stimulating factor (G-CSF), which promotes the proliferation of neutrophils; and macrophage colony-stimulating fac- tor (M-CSF), which induces macrophage colonies. 3–5 Other cytokines, such as the interleukins, interferons, and tumor necrosis factor, support the proliferation of stem cells and the development of lymphocytes and act synergistically to aid the multiple functions of the CSFs. The genes for most hematopoietic growth factors have been cloned and their recombinant proteins have been generated for use in a wide range of clinical condi- tions. The clinically useful factors include EPO, G-CSF, and GM-CSF. 5 They are used for treatment of bone mar- row failure caused by chemotherapy or aplastic anemia, the anemia of kidney failure and cancer, hematopoietic neoplasms, infectious diseases such as acquired immu- nodeficiency syndrome (AIDS), and congenital and myeloproliferative disorders. Growth factors are used

to increase peripheral stem cells for transplantation and to accelerate cell proliferation after bone marrow engraftment.

Leukocytes (White Blood Cells) The leukocytes or white blood cells, which are the focus of this chapter, originate in the bone marrow and cir- culate throughout the lymphoid tissues of the body. Leukocytes are commonly classified into two groups based on the presence or absence of specific prominent granules in their cytoplasm. 1,2 Those containing specific granules (neutrophils, eosinophils, basophils) are classi- fied as granulocytes, and those that lack granules (lym- phocytes and monocytes) as agranulocytes (Fig. 11-2). The granulocytes and the agranular monocytes/macro- phages are derived from the myeloid stem cells in the bone marrow and circulate in the blood (see Fig. 11-1). The lymphocytes originate from lymphoid stem cells in the bone marrow and migrate between the blood and the lymphatic system. Granulocytes Granulocytes are spherical and have distinctive multilo- bar nuclei. They are all phagocytic cells that are identifi- able because of their cytoplasmic granules. They have two types of granules: specific granules that bind neu- tral, basic, or acidic dye components, and azurophilic

Granulocytes

Erythrocyte

Nucleus

Nucleus Granules

Granules Nucleus

Erythrocyte

A Neutrophil

C Basophil

B Eosinophil

Agranulocytes

Platelet

Erythrocyte

Nucleus

Nucleus

Erythrocyte

E Monocyte

D Lymphocyte

FIGURE 11-2. White blood cells. Granulocytes (A–C) and agranulocytes (D, E) . (A) The neutrophil has a large, segmented nucleus. (B) The eosinophil has many bright red–staining granules. (C) The basophil has large dark blue–staining granules. (D) The lymphocyte has a large undivided nucleus. (E) The monocyte is the largest of the leukocytes. (From Cohen BJ. Memmler’sThe Human Body in Health and Disease. 11th ed. Baltimore, MD:Wolters Kluwer Health ǀ LippincottWilliams &Wilkins; 2009:284.)