Reactive (Inflammatory) Proliferations of White Cells and Lymph Nodes

LEUKOCYTOSIS

Leukocytosis refers to an increase in the number of blood leukocytes. It is a common reaction to a variety of inflammatory states and is sometimes the first indication of neoplastic growth

of leukocytes.

Pathogenesis.

The peripheral blood leukocyte count is influenced by several factors, including:

• The size of the myeloid (for granulocytes and monocytes) and lymphoid (for lymphocytes) precursor and storage cell pools in the bone marrow, circulation, and peripheral tissues

• The rate of release of cells from the storage pool into the circulation

• The proportion of cells that are adherent to blood vessel walls at any time (the marginating pool)

• The rate of extravasation of cells from the blood into tissues

As was discussed in Chapter 2 and Chapter 13 , leukocyte homeostasis is maintained by cytokines, growth factors, and adhesion molecules through their effects on the commitment,

proliferation, differentiation, and extravasation of leukocytes and their progenitors. The mechanisms of leukocytosis vary

Figure 14-1(Figure Not Available) Mechanisms of neutrophilic leukocytosis. Neutrophils and their precursors are distributed in five pools: a bone marrow precursor pool; a bone marrow

storage pool, consisting of mature and slightly immature neutrophils (band forms); a peripheral blood marginating pool; a peripheral blood circulating pool; and a tissue pool. Sampling of

the peripheral blood assesses only the circulating pool, which can be enlarged by increased release of neutrophils and band forms from the marrow storage pool, decreased margination,

diminished extravasation into tissues, or expansion of the marrow precursor cell pool. Diverse stimuli that increase the circulating pool through various mechanisms are listed. It should be

noted that certain stimuli (e.g., acute infection) cause changes in flux between multiple pools simultaneously.

depending on the affected leukocyte pool and the particular factor. In acute infection, there is a rapid increase in the egress of mature granulocytes from the bone marrow pool, which is

roughly 50 times the size of the peripheral blood marginal pool. The release of IL-1, TNF, and other inflammatory cytokines stimulates bone marrow stromal cells and T cells to produce

increased amounts of colony-stimulating factors (CSFs), which enhance the proliferation and differentiation of committed granulocytic progenitors and, over several days, cause a sustained

increase in neutrophil production. Figure 14-1 (Figure Not Available) summarizes the major mechanisms of neutrophilic leukocytosis and their causes.

TABLE 14-1-- Causes of Leukocytosis

Neutrophilic leukocytosis Acute bacterial infections, especially those caused by pyogenic organisms; sterile inflammation caused by, for example, tissue necrosis (myocardial

infarction, burns)

Eosinophilic leukocytosis

(eosinophilia)

Allergic disorders such as asthma, hay fever, allergic skin diseases (e.g., pemphigus, dermatitis herpetiformis); parasitic infestations; drug reactions;

certain malignancies (e.g., Hodgkin disease and some non-Hodgkin lymphomas); collagen vascular disorders and some vasculitides; atheroembolic

disease (transient)

Basophilic leukocytosis

(basophilia)

Rare, often indicative of a myeloproliferative disease (e.g., chronic myelogenous leukemia)

Monocytosis Chronic infections (e.g., tuberculosis), bacterial endocarditis, rickettsiosis and malaria; collagen vascular diseases (e.g., systemic lupus erythematosus)

and inflammatory bowel diseases (e.g., ulcerative colitis)

Lymphocytosis Accompanies monocytosis in many disorders associated with chronic immunologic stimulation (e.g., tuberculosis, brucellosis); viral infections (e.g.,

hepatitis A, cytomegalovirus, Epstein-Barr virus); Bordetella pertussis infection

Other growth factors preferentially stimulate other types of leukocytosis. For example, IL-5 causes eosinophilia by enhancing the growth, survival, and differentiation of eosinophils, while

IL-7 plays a central role in lymphopoiesis. Such factors are differentially produced in response to various pathogenic stimuli, and as a result, the five principal types of leukocytosis

(neutrophilic, eosinophilic, and basophilic leukocytosis, monocytosis, and lymphocytosis) each tend to be observed in particular clinical settings (summarized in Table 14-1 ).

In sepsis or severe inflammatory disorders (such as Kawasaki disease), leukocytosis is often accompanied by morphologic

changes in the neutrophils, such as toxic granulations, Döhle bodies, and cytoplasmic vacuoles ( Fig. 14-2 ). Toxic granules are coarse and darker than the normal neutrophilic granules and

are believed to represent abnormal azurophilic (primary) granules. Döhle bodies are patches of dilated endoplasmic reticulum that appear as sky-blue cytoplasmic "puddles" in smears

stained with Wright-Giemsa stain.

In most instances, it is not difficult to distinguish reactive leukocytosis from leukocytosis caused by flooding of the peripheral blood by neoplastic white blood cells (leukemia), but

uncertainties may arise in two settings. Particularly in children, acute viral infections can produce the appearance of activated lymphocytes in the peripheral blood and marrow that

resemble neoplastic lymphoid cells. At other times, particularly in inflammatory states and severe chronic infections, many immature granulocytes appear in the blood, simulating a picture

of myelogenous leukemia (leukemoid reaction). Special laboratory studies (discussed later) are helpful in distinguishing reactive and neoplastic leukocytoses.

In addition to causing leukocytosis, infections and inflammatory stimuli often elicit immune reactions within lymph nodes. The infections that lead to lymphadenitis are numerous. Some

that produce distinctive morphologic patterns are described in other chapters. Most, however, cause stereotypic patterns of lymph node reaction designated acute and chronic nonspecific

lymphadenitis.

Date: 2016-04-22; view: 1023