Page 1025 - Williams Hematology ( PDFDrive )

1000 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 65: Neutropenia and Neutrophilia 1001

solely to this mechanism. The increase in lymphocytes, monocytes, and cell production follows stimulation of cell divisions within the mitotic
neutrophils that occurs with demargination may be helpful in distin- precursor pool, that is, divisions of promyelocytes and myelocytes. Sub-
guishing this type of neutrophilia from the response to infections, pro- sequently, the size of the postmitotic pool increases. The changes cause
tracted stress, or glucocorticoid administration. With these conditions, an increase in the marrow granulocytic to erythroid ratio. In humans,
neutrophil counts are elevated, but lymphocyte and monocyte counts the neutrophil production rate increases severalfold with chronic infec-
generally are depressed. tions. Even greater increases may occur in polycythemia vera, chronic
Marrow Storage Pool Shift Acute neutrophilia occurs as a con- myelogenous leukemia, and leukemoid reactions in response to nonhe-
142
sequence of release of neutrophils from the marrow storage pool, the matologic malignancies and to exogenously administered hematopoi-
139
marrow neutrophil reserves. This mechanism produces acute neu- etic growth factors such as G-CSF, 140,141 with a maximum response taking
trophilia in response to inflammation and infections. The marrow at least 1 week to develop.
reserve pool consists principally of segmented neutrophils and bands. Neutrophilia resulting from decreased egress from the vascular
Metamyelocytes are not released to the blood except under extreme compartment occurs infrequently. A prototype disorder illustrating
circumstances. The postmitotic marrow neutrophil pool is approx- this mechanism occurs in patients with the neutrophil cell membrane
143
imately 10 times the size of the blood neutrophil pool, and approx- defect CD11a/CD18 deficiency. The neutrophils do not adhere to
135
imately half of these cells are band and segmented neutrophils. the capillary endothelium normally, but cell production and marrow
In neutrophil production disorders, chronic inflammatory diseases, release apparently are normal. Because these patients cannot mobilize
and malignancies, and with cancer chemotherapy, the size of this neutrophils to sites of inflammation when they develop infections,
pool is reduced and the capacity to develop neutrophilia is impaired. extreme neutrophilia is observed (Chap. 66). Glucocorticoids may pro-
Exposure of blood to foreign surfaces, such as hemodialysis mem- duce a functionally similar state, with neutrophils accumulating in the
branes, activates the complement system and causes transient neu- blood, at least transiently, after each dose is administered. In patients
144
tropenia, followed by neutrophilia resulting from release of marrow recovering from infections, as the “tissue demand” for neutrophils
neutrophils. Colony-stimulating factors (G-CSF and GM-CSF) cause diminishes, the persistence of neutrophilia may be attributed to this
acute and chronic neutrophilia by mobilizing cells from the marrow same mechanism. In chronic myelogenous leukemia, accumulation of
reserves and stimulating neutrophil production. 140,141 neutrophils with a longer than normal half-life in the blood partially
explains the extreme neutrophilia. 145
Chronic Neutrophilia
Chronic neutrophilia follows a prolonged stimulus to proliferation of DISORDERS ASSOCIATED WITH NEUTROPHILIA
neutrophil precursors. It can be studied experimentally with repeated
doses of endotoxin, glucocorticoids, or colony-stimulating factors. Neutrophilia in Response to Inflammation and Stress
Although the details of the mediators and mechanisms for the develop- Table 65–2 lists the categories and causes of acute and chronic neu-
ment of chronic neutrophilia are not understood fully, a general scheme trophilia. Probably the most frequent causes of acute neutrophilia
for this response is now widely accepted (see Fig. 65–4). Expansion of are exercise, emotional stress, and any other circumstance that raises

TABLE 65–2. Major Causes of Neutrophilia
Acute Neutrophilia Chronic Neutrophilia
Physical stimuli Infections
Cold, heat, exercise, convulsions, pain, labor, anesthesia, Persistence of infections that cause acute neutrophilia
surgery Inflammation
Emotional stimuli Most acute inflammatory reactions, such as colitis, dermatitis, drug-
Panic, rage, severe stress, depression sensitivity reactions, gout, hepatitis, myositis, nephritis, pancreatitis,
Infections periodontitis, rheumatic fever, rheumatoid arthritis, vasculitis, thy-
Many localized and systemic acute bacterial, mycotic, rickettsial, roiditis, Sweet syndrome
spirochetal, and certain viral infections Tumors
Inflammation or tissue necrosis Gastric, bronchogenic, breast, renal, hepatic, pancreatic, uterine, and
Burns, electric shock, trauma, infarction, gout, vasculitis, anti- squamous cell cancers; rarely Hodgkin lymphoma, lymphoma, brain
tumors, melanoma, and multiple myeloma
gen-antibody complexes, complement activation
Drugs, hormones, and toxins Drugs, hormones, and toxins
Colony-stimulating factors, epinephrine, etiocholanolone, Continued exposure to many substances that produce acute neu-
trophilia, lithium; rarely as a reaction to other drugs
endotoxin, glucocorticoids, smoking tobacco, vaccines, venoms
Metabolic and endocrinologic disorders
Eclampsia, thyroid storm, overproduction of adrenocorticotropic
hormone
Hematologic disorders
Rebound from agranulocytosis or therapy of megaloblastic anemia,
chronic hemolysis or hemorrhage, asplenia, myeloproliferative disor-
ders, chronic idiopathic leukocytosis
Hereditary and congenital disorders
Down syndrome, congenital

Kaushansky_chapter 65_p0991-1004.indd 1000 9/17/15 6:44 PM