After studying this chapter, you should understand:
The factors that determine leukocyte counts in the peripheral blood.
The major causes of granulocytosis (neutrophilia) and other forms of leukocytosis.
The causes and consequences of leukopenia.
The mechanisms underlying qualitative disorders of neutrophil function.
The causes and consequences of hemophagocytic lymphohistiocytosis (macrophage activation syndrome).
Leukocytes constitute the cellular components of the innate and adaptive immune system and are critical for host defense. These cells mediate acute and chronic inflammation, modulate immune responses, and protect the host against numerous pathogens. It is no surprise that defects in leukocyte function predispose to various kinds of infection in proportion to the nature and severity of the defect.
Disorders affecting leukocytes can be divided broadly into malignant disorders (tumors of leukocytes or their progenitors) and nonmalignant disorders. The malignant disorders are uncommon but clinically important entities that are covered in subsequent chapters. Here we consider the much more common nonmalignant abnormalities that affect leukocytes. These can involve any of the leukocytes (neutrophils, eosinophils, basophils, monocytes, B cells, T cells, and natural killer cells), but the disorders of greatest clinical relevance affect neutrophils; these will be our major focus.
OVERVIEW OF NEUTROPHIL DISORDERS
Like other formed elements of the peripheral blood, neutrophils are the progeny of earlier progenitors that acquire the capacity to function as they mature in the bone marrow (Figure 18-1). Neutrophils are distributed within the body in several discrete and highly dynamic compartments or pools (Figure 18-2). In the marrow, mitotically active myeloid progenitors mature over a period of 7 to 10 days to give rise to large numbers of neutrophils. Under steady-state conditions, most of these newly formed neutrophils die without ever being released into the blood, constituting a storage pool that can be called upon during times of increased need. Upon release from the marrow, neutrophils enter the circulating pool, the only pool that is measured clinically. On average, neutrophils circulate for less than 24 hours before migrating into tissues, where they may survive for up to 3 days. At any given time, roughly half of the neutrophils in the blood are adherent to vessel walls; these cells are referred to as the marginal pool. Finally, some circulating neutrophils are sequestered in the spleen. Normally, <5% of the neutrophils in the body are in the circulating pool, which turns over quickly. As a result, stimuli that alter the release of neutrophils from the marrow, neutrophil margination, or the migration of neutrophils into tissues can have rapid and sometimes profound effects on the peripheral blood neutrophil count.
Myelopoiesis. As granulocytes develop and mature, they go through a series of recognizable morphologic stages that correlate with the expression of genes that confer the specific functions indicated on the time line. HSC, hematopoietic stem cell; PMN, polymorphonuclear leukocyte. (Used with permission from Gaines P, Berliner N. Granulocytopoiesis. In Young N, ed. Clinical Hematology. Philadelphia: Mosby/Elsevier, 2006, p. 62.)
Neutrophil pools. The relative proportions of cells in various pools of neutrophils and neutrophilic progenitors are shown ...