Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

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is the respiratory tract, a result of bacteria or fungi that frequently colonize the airways. Untreated infections can be rapidly fatal, particularly if the neutrophil count is less than 250/ μ L. In the presence of severe neutropenia, the usual signs of inflammatory response to infection may be absent. Nevertheless, fever in the person with neutropenia should always be assumed to be of infec- tious origin. A characteristic feature of bacterial infec- tion in persons with neutropenia is the absence of pus, a purulent drainage containing leukocytes, dead cells, and tissue elements that have been liquefied by proteolytic enzymes elaborated by the neutrophils. 11 Antibiotics are used to treat infections in those situa- tions in which neutrophil destruction can be controlled or the neutropoietic function of the bone marrow can be recovered. Hematopoietic growth factors such as recombinant human G-CSF may be used to stimulate the maturation and differentiation of the granulocytic cell line. 8–11 Infectious Mononucleosis Infectious mononucleosis is a self-limiting lymphop- roliferative disorder caused by the Epstein-Barr virus (EBV), a member of the herpesvirus family. 12–15 The term EBV-associated infectious mononucleosis is often used to designate infectious mononucleosis caused by EBV as opposed to non–EBV-associated clinical syn- dromes of infectious mononucleosis caused by other agents. Infectious mononucleosis may occur at any age, but occurs principally in adolescents and young adults in developed countries. Epstein-Barr virus is one of the viruses that is most successful in evading the immune system, infecting about 90% of humans and persisting for the lifetime of the person. Epstein-Barr virus spreads from person to person primarily through contact with infected oral secretions. Transmission requires close contact with infected persons. Thus, the virus spreads readily among young children in crowded conditions, where there is considerable sharing of oral secretions. Kissing is also an effective mode of transmission. 15 Pathogenesis Infectious mononucleosis is largely transmitted through oral contact with EBV-contaminated saliva. The virus ini- tially penetrates the nasopharyngeal, oropharyngeal, and salivary epithelial cells. It then spreads to the underlying oropharyngeal lymphoid tissue and, more specifically, to B lymphocytes, all of which have receptors for EBV. 12–15 Infection of the B cells may take one of two forms—it may kill the infected B cell, or the virus may incorporate itself into the cell’s genome. The B cells that harbor the EBV genome proliferate in the circulation and produce the well-known heterophil antibodies that are used for the diagnosis of infectious mononucleosis. A heterophil antibody is an immunoglobulin that reacts with antigens from another species—in this case, sheep red blood cells. The normal immune response is important in con- trolling the proliferation of the EBV-infected B cells with the CD8 + cytotoxic T cells and NK cells playing

the pivotal role. These virus-specific T cells appear as large, atypical lymphocytes that are characteristic of the infection (Fig. 11-5). In otherwise healthy persons, the humoral and cellular immune responses serve to control viral shedding by limiting the number of infected B cells rather than eliminating them. Although infected B cells and free virions disappear from the blood after recovery from the disease, the virus remains in a few transformed B cells in the oropharyn- geal region and is shed in the saliva. Once infected with the virus, persons remain asymptomatically infected for life, and a few such persons intermittently shed EBV. Immunosuppressed persons shed the virus more frequently. Asymptomatic shedding of EBV by healthy persons is thought to account for most of the spread of infectious mononucleosis, despite the fact that it is not a highly contagious disease. Clinical Course The onset of infectious mononucleosis usually is insidi- ous. The incubation period from time of initial exposure to onset of symptoms is estimated at 4 to 8 weeks. 15 A prodromal period, which lasts for several days, fol- lows and is characterized by malaise, anorexia, and chills. The prodromal period precedes the onset of fever, pharyngitis, and lymphadenopathy. Occasionally, the disorder comes on abruptly with a high fever. Most persons seek medical attention for severe pharyngitis, which usually is most severe on days 5 to 7 and per- sists for 7 to 14 days. The lymph nodes are typically enlarged throughout the body, particularly in the cervi- cal, axillary, and groin areas. Hepatitis and splenomeg- aly are common manifestations of the disease and are thought to be immune mediated. Hepatitis is character- ized by nausea, anorexia, hepatomegaly, and jaundice. Although discomforting, it usually is a benign condi- tion that resolves without causing permanent liver dam- age. The spleen may be enlarged two to three times its

FIGURE 11-5. Infectious mononucleosis. Atypical lymphocytes are characteristic. (FromValdez R, Zutter M, Dulau FA, Rubin R. Hematopathology. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams & Wilkins; 2012:1002.)