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 (Fig. 18-1). Neutrophils are distributed within the body in several discrete and highly dynamic compartments or pools (Fig. 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 only 3 to 6 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 (Used with permission from Gaines P and Berliner N. Granulocytopoiesis. In Clinical Hematology, Young N, ed, Philadelphia, USA, Mosby/Elsevier, 2006, 62.)
Neutrophil pools. The relative proportions of cells in various pools of neutrophils and neutrophilic progenitors are shown (see text for details).
In most clinical laboratories, the normal white blood cell count ranges from 4500 to 11,000/μL, with approximately 60% of the cells being neutrophils. Leukocytosis, an elevation in the white blood cell count, usually stems from a pathologic insult that stimulates a systemic inflammatory reaction. By far the most common form of leukocytosis is granulocytosis, an increase in neutrophils also known as neutrophilia.
Acute inflammation of any cause can produce the rapid appearance of granulocytosis by mobilizing neutrophils from the marrow storage pool. In particularly severe bacterial infections, immature granulocytic forms, such as band cells or even earlier progenitors, may be released into the blood (a finding also called a left-shift), and in extreme cases the white blood cell count may rise to >50,000/mm3. In such instances the marked leukocytosis and the presence of immature cells may mimic the appearance of a myeloid leukemia (leukemoid reaction). Occasionally, the inflammatory process may involve the marrow itself and produce marrow fibrosis and distortion, leading not only to the release of immature myeloid elements but also nucleated erythroid progenitors and misshapen tear-drop red cells. This combination of features in a peripheral smear is referred to as leukoerythroblastosis. If the marrow involvement is extensive, myelophthisic anemia may result (Chapter 4). It should be emphasized, however, that in the vast majority of cases granulocytosis is a reaction to disorders involving tissues other than the marrow. In contrast, neutropenia, an abnormally low neutrophil count, is often caused by defects in neutrophil production that may require a bone marrow examination for evaluation.
Primary disorders associated with neutrophil dysfunction usually have a genetic basis. Although rare, they are of interest because unraveling of their pathogenesis has led to the identification of genes that regulate normal neutrophil development and function.