Alterations of Leukocyte and Lymphoid Function - McCance 30 PDF

**C H A P T E R** 30 **Alterations of Leukocyte and** **Lymphoid Function** - Content Updates - Chapter Summary Review - Review Questions - Case Studies - Animations Lymphoid Neoplasm: Leukemias, 968 **Alterations of Lymphoid Function, 976** [ALTERATIONS OF LEUKOCYTE FUNCTION ]...

**C H A P T E R** 30 **Alterations of Leukocyte and** **Lymphoid Function** - Content Updates - Chapter Summary Review - Review Questions - Case Studies - Animations Lymphoid Neoplasm: Leukemias, 968 **Alterations of Lymphoid Function, 976** [ALTERATIONS OF LEUKOCYTE FUNCTION ] ================================================ Quantitative Alterations of Leukocytes -------------------------------------- ### Granulocytes and Monocytes -- -- -- -- -- -- ### Lymphocytes Infectious Mononucleosis ------------------------ Lymphoid Neoplasm: Leukemias ---------------------------- 1. Precursor B-cell neoplasms (immature B cells) 2. Peripheral B-cell neoplasms (mature B cells) 3. Precursor T-cell neoplasms (immature T cells) 4. Peripheral T-cell and NK-cell neoplasms (mature T cells and NK cells 5. Hodgkin lymphoma (Reed-Sternberg cells and variants) ##### B ### Acute Leukemias ##### A ##### B ### TABLE 30.2 CLINICAL MANIFESTATIONS AND RELATED PHYSIOLOGY IN LEUKEMIA ### Chronic Leukemias RAS *BCR-ABL* fusion mRNA [ALTERATIONS OF LYMPHOID FUNCTION ] =============================================== Lymphadenopathy --------------- Malignant Lymphomas ------------------- ### Hodgkin Lymphoma ### BOX 30.2 WORLD HEALTH ORGANIZATION CLASSIFICATION OF LYMPHOID NEOPLASMS -- -------------------------------------------------- -- Found in all ages but most common in adolescents and young adults (median age of onset is about -- -------------------------------------------------- -- ### Non-Hodgkin Lymphoma ### Burkitt Lymphoma ### Lymphoblastic Lymphoma **PATHOPHYSIOLOGY.** The disease arises from a clone of relatively immature T cells that becomes malignant in the thymus. As with most pro-growth genes ### Conditions That Mimic Lymphomas Macro 2% (38) Solitary or extra- medullary 1% (20) ##### B Plasma Cell Malignancies ------------------------ ### Multiple Myeloma   ### Waldenström Macroglobulinemia [ALTERATIONS OF SPLENIC FUNCTION ] ============================================== #### Alterations of Leukocyte Function 1. Quantitative alterations of leukocytes (too many or too few) can be caused by bone marrow dysfunction or premature destruction of cells in the circulation. Many quantitative changes in leukocytes occur in response to invasion by microorganisms. 2. Leukocytosis is a leukocyte count higher than normal and is usually a response to physiologic stressors, malignancies and hematologic disorders, and invasion of microorganisms. 3. Leukopenia is a leukocyte count lower than normal, is associated with neutropenia and infection, and is caused by physiologic stressors and by pathologic conditions such as malignancies and hematologic disorders. 4. Granulocytosis (particularly as a result of an increase in the number of neutrophils) occurs in response to infection. The marrow releases immature cells, causing a shift-to-the-left when responding to an infection that has created a demand for neutrophils that exceeds the supply in the circulation. 5. Eosinophilia results most commonly from parasitic invasion and ingestion or from inhalation of toxic foreign particles. 6. Basophilia is seen in hypersensitivity reactions because of the high 7. Monocytosis occurs during the late or recuperative phase of infection when macrophages (mature monocytes) phagocytose surviving microorganisms and debris. Monocytosis is often seen in chronic infections, usually with intracellular bacteria, such as tuberculosis (TB), brucellosis, listeriosis, and subacute bacterial endocarditis (SBE). Peripheral monocytosis has been found to correlate with the extent of myocardial damage following myocardial infarction. Increased numbers of monocytes also may indicate marrow recovery from agranulocytosis. 8. Granulocytopenia, a significant decrease in the number of neu- trophils, can be a life-threatening condition if sepsis occurs; it is often caused by chemotherapeutic agents, severe infection, and radiation. 9. The number of lymphocytes is decreased (lymphocytopenia) in most acute infections and in some immunodeficiency syndromes. 10. Lymphocytosis occurs in viral infections (IM and infectious hepatitis, in particular), leukemia, lymphomas, and some chronic infections. 11. Infectious mononucleosis is an acute infection of B lymphocytes most commonly associated with EBV, a type of herpesvirus. Transmission of EBV is by personal contact, commonly through saliva (e.g., kissing, hence its nickname "kissing disease"). 12. Two of the earliest manifestations of mononucleosis are sore throat and fever caused by inflammation at the primary site of viral entry. It is self-limiting and treatment consists of rest and relief of symptoms. 13. EBV is associated with several tumors including lymphomas and 14. Leukemia is a clonal disorder of leukocytes in the bone marrow, and usually of the blood. The common pathologic feature of all forms of leukemia is an uncontrolled proliferation of leukocytes and overcrowding of the bone marrow, causing a decreased produc- tion and function of the other blood cell lines. 15. All leukemias are classified by the cell type involved: B cells, T cells, and NK cells. They are differentiated by onset: acute or chronic. Overall, there are four major types of leukemia: ALL, CLL, AML, and CML. With increased understanding, the distinct divisions between leukemia and lymphoma have become indistinct and blurred. Conditions known as "lymphoma" that arise as a discrete tissue mass sometimes have "leukemic" presentations and progres- sion to leukemia is not unusual during the progression of incurable lymphomas. 16. Although the exact cause of leukemia is unknown, it is considered a clonal disorder. A higher incidence of acute leukemias and CLL is reported in certain families, suggesting a possible genetic pre- disposition. Risk factors have been linked to exposure to cigarette smoke, benzene, and ionizing radiation. 17. The most common genetic abnormality in adult ALL is the 18. Genetic aberrations in AML alter genes encoding transcription factors needed for normal myeloid differentiation and arrest dif- ferentiation. These mutations affect the epigenome, suggesting that epigenetic alterations are key in AML. 19. The major clinical manifestations of leukemia include fatigue caused by anemia, bleeding caused by thrombocytopenia, fever secondary to infection, anorexia, and weight loss. Chronic leukemias 20. Chemotherapy is the treatment of choice for leukemia. New targets or drugs have been reported to inhibit leukemia stem cells both in vitro and in vivo. #### Alterations of Lymphoid Function 1. The number of lymphocytes is decreased (lymphocytopenia) in most acute infections and in some immunodeficiency syndromes. 2. Lymphocytosis occurs in viral infections (IM and infectious hepatitis, in particular), leukemia, lymphomas, and some chronic infections. 3. Lymphomas are tumors of primary lymphoid tissue (thymus, bone marrow) or secondary lymphoid tissue (lymph nodes, spleen, tonsils, intestinal lymphoid tissue). The two major types of malignant lymphomas are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). 4. Reed-Sternberg (RS) cells in lymph nodes are classically associated with HL. The RS cell is derived from a malignant B cell that usually becomes binucleate. 5. A virus might be involved in the pathogenesis of HL. Some familial clustering suggests an unknown genetic mechanism. 6. An enlarged painless mass or swelling, most commonly in the neck, is an initial sign of HL. Local symptoms are produced by lymphadenopathy, usually caused by pressure or obstruction. 7. Treatment of HL includes radiation therapy and chemotherapy. 8. The cause of lymph node enlargement and cancerous transforma- tion in NHL is unknown. Factors associated with industrialization and economic improvement may be linked to the incidence of lymphoma, geographically. In general, lymphomas are the result of genetic mutations or viral infection. Immunosuppressed persons have a higher incidence of NHL, suggesting an immune mechanism. 9. Generally, with NHL the swelling of lymph nodes is painless, and 10. Individuals with NHL can survive for long periods. Treatment is 11. Burkitt lymphoma involves the jaw and facial bones and occurs in children from east-central Africa and New Guinea. In the United States, Burkitt lymphoma is rare, usually involves the abdomen, and is characterized by extensive bone marrow invasion and replacement. 12. Multiple myeloma (MM) is a neoplasm of B cells (immature plasma cells) and mature plasma cells. It is characterized by multiple malignant tumors of plasma cells scattered throughout the skeletal system and occasionally in soft tissue. 13. Myeloma cells usually secrete monoclonal protein (M protein) that is an abnormal antibody molecule. The myeloma cell may also secrete free antibody light chain that is excreted in the urine (Bence Jones protein). 14. The exact cause of MM is unknown. Risk factors include exposure to radiation or certain chemicals and a history of monoclonal gammopathy of undetermined significance (MGUS). 15. The major clinical manifestations for MM include recurrent infec- tions caused by suppression of the humoral immune response and renal disease as a result of Bence Jones proteinuria. 16. Chemotherapy is the treatment of choice for MM. Other therapies include stem cell transplantation, biologic therapy, radiation therapy, and sometimes surgery. 17. Waldenström macroglobulinemia is a rare type of slow-growing #### Alterations of Splenic Function 1. 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