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Alterations of Hematologic Function – Part 2 Leukocytes and Thrombocytes I

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Alterations of Hematologic Function – Part 2 Leukocytes and Thrombocytes I PATHOPHYSIOLOGY Name Chapter 20: Alterations of Hematologic Function – Part 2 Leukocytes and Thrombocytes I. Alterations of Leukocyte Function A. Quantitative Alterations of Leukocytes Increases or decreases in cell numbers o ―-cytosis‖ or ―-philia‖ refer to an increase in number. o ―-openia‖ refers to a decrease in number. Leukocytosis – higher than normal leukocyte count. o Leukocytosis is a normal protective physiologic response to physiologic stressors, including infection. Leukopenia – lower than normal leukocyte count. o Leukopenia is not normal and not beneficial o A low white count predisposes a patient to infections. 1. Granulocytosis Increased numbers of granulocytes (neutrophils, eosinophils, and basophils) in the blood. 3 Neutrophilia is evident in the first stages of an infection or inflammation (count >7,500/mm ). If the need for neutrophils increases beyond the supply, immature neutrophils (banded neutrophils) are released into the blood. This premature release is detected in the manual WBC differential and is termed a shift-to-the-left. When the population returns to normal, it is termed a shift-to-the-right. 2. Neutropenia Reduction in circulating neutrophils less than 2000/mm3. Causes: o Prolonged severe infection o Decreased production o Reduced survival o Abnormal neutrophil distribution and sequestration 3. Granulocytopenia (Agranulocytosis) Very low numbers of granulocytes with neutrophil counts below 500/ mm3. Greatly increases risk of infection. Causes of granulocytopenia: o Interference with hematopoiesis o Immune mechanisms o Chemotherapy destruction o Ionizing radiation 4. Eosinophilia Hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of anaphylaxis from mast cells. Occurs in allergic disorders and parasitic invasions. 2 5. Eosinopenia Usually caused by migration of cells to inflammatory sites. Other causes - surgery, shock, trauma, burns, or mental distress. 6. Basophilia Basophils account for only 0% to 1% of the circulating WBCs Basophilia occurs in response to inflammation and hypersensitivity reactions. 7. Basopenia Occurs in acute infections, hyperthyroidism, and long-term steroid therapy 8. Monocytosis Poor correlation with disease. Usually occurs with neutropenia in later stages of infections. Monocytes are needed to phagocytize organisms and debris. 9. Monocytopenia Very little known about this condition. Associated with hairy cell leukemia and prednisone therapy. 10. Lymphocytosis Occurs in acute viral infections. 11. Lymphocytopenia Occurs in immune deficiencies, drug destruction, viral destruction. ACTIVITY 1: Match the type of infection or disorder with the most likely leukocyte alteration. 1. Bacterial infection. a. Eosinophilia 2. Allergic reaction. b. Granulocytosis 3. Viral infection. c. Lymphocytosis 4. Parasitic infection. 12. Infectious Mononucleosis Acute, self-limiting infection of B-lymphocytes. Caused by the Epstein-Barr virus (EBV). Transmitted in saliva through personal contact. Manifestations: o Initially - fever, sore throat, swollen cervical lymph nodes, headache, fatigue, joint aches, increased lymphocyte count, and atypical (activated) lymphocytes. o Later – generalized lymph node enlargement, enlargement of liver and spleen (hepatomegaly and splenomegaly). Serious complications are infrequent (<5%). o Splenic rupture is the most common cause of death. Diagnostic test - monospot qualitative test for heterophilic antibodies Treatment - for relief of symptoms; bed rest; limit physical activity to avoid rupture of spleen. Usually self-limiting with fatigue lasting for 1-2 months after other symptoms resolve. 3 B. Qualitative Alterations of Leukocytes Leukemia - neoplastic proliferation of leukocyte precursor cells in the bone marrow. o Results in dysfunctional progeny cells. o Interferes with the production of other blood cells in the marrow. Pathophysiology: o Mutations in a leukocyte precursor cell cause unregulated cellular proliferation. o Believed to occur in individuals with an inherited chromosomal vulnerability to mutagens such as radiation, toxins, or chemotherapeutic agents. o There is a blockage of the normal differentiation of the cell so that it continues to divide (―immortal cell‖); not an increase in the rate of cell division. o These cells accumulate in the marrow, crowding out the other marrow cells and eventually spilling out into the peripheral blood. o Leukemic cells are not capable of normal white blood cell function; this, combined with decreased production of erythrocytes and platelets, leads to the common complications of leukemia: . Infection, anemia, and bleeding. Risk factors for leukemia: o Family history of leukemia o Certain hereditary abnormalities, including Down syndrome o Some immune deficiencies o Environmental factors like cigarette smoke, benzene, and ionizing radiation o Viral infections by HIV, hepatitis C, and HTLV-1 o Drugs that suppress bone marrow, including many chemotherapy agents Classifications of leukemia: o Acute - presence of undifferentiated or immature cells, usually blast cells o Chronic - predominant cell is mature but does not function normally o Myelogenous - arise from precursors of the granulocytes o Lymphocytic - arise from precursors of lymphocytes 1. Acute leukemias: a. Acute lymphocytic leukemia (ALL) . More common in children. Clinical Manifestations - recurrent infections, anemia, and thrombocytopenia; failure to thrive and difficulty in swallowing are also common manifestations. Lymphadenopathy (lymph node enlargement) and hepatosplenomegaly may occur in ALL. 4 b. Acute myelogenous leukemia (AML) . More common in middle-aged individuals. Clinical Manifestations - o Recurrent infections (fever, cough, dysuria, pharyngitis, diarrhea) o Anemia (fatigue, pallor, dizziness, and shortness of breath) o Thrombocytopenia (petechiae and hemorrhaging) o Also anorexia, weight loss, and neurologic symptoms (headache, stroke, meningitis). o Treatment of acute leukemia includes: . Chemotherapy . Bone marrow transplantation (if chemotherapy is not effective) o In ALL, chemotherapy results in cure in the majority of children. o In AML, relapse is common and requires consideration for bone marrow transplantation. Supportive care, including red blood cell transfusions, platelet transfusions, and antibiotics. 2. Chronic leukemias: a. Chronic myelogenous leukemia (CML) . More common in middle-aged to older adults. Commonly associated with a specific chromosomal translocation called the Philadelphia chromosome which contains a BRC-ABL gene fusion. b. Chronic lymphocytic leukemia (CLL) . Occurs primarily in the elderly. Usually the result of neoplastic proliferation of a B-lymphocyte precursor. Not associated with the Philadelphia chromosome mutation. o Clinical manifestations of chronic leukemia: . Fatigue, weight loss . Low-grade fever, night sweats . Splenomegaly, possible abdominal discomfort . Adenopathy (most common in CLL) o Because the neoplastic cells are more differentiated than in acute leukemia, chronic leukemia tends to have a more slowly progressive course. o Treatment depends on the type of leukemia and the age of the affected individual, but usually includes low-dose chemotherapy or radiation. ACTIVITY 2: Match the characteristic with the type of leukemia it is associated with. 1. Presence of Philadelphia chromosome. a. Acute lymphocytic leukemia 2. Most common in children. b. Acute myelogenous leukemia 3. Slowly progressive; occurs mainly in elderly. c. Chronic myelogenous leukemia 4. Rapidly progressive; occurs mainly in middle age. d. Chronic lymphocytic leukemia 5 II. Alterations of Lymphoid Function A. Lymphadenopathy Enlarged lymph nodes that become palpable and tender. Local lymphadenopathy - due to drainage of an inflammatory lesion near the enlarged node. General lymphadenopathy - occurs in the presence of malignant or nonmalignant disease. B. Malignant Lymphomas Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues Two major categories - Hodgkin lymphoma (HL) and Non-Hodgkin lymphomas (NHL) 1. Hodgkin Lymphoma Characterized by the presence of Reed-Sternberg cells in the lymph nodes. Generally presents with lymphadenopathy, usually beginning in the neck. Physical findings - adenopathy, mediastinal mass, splenomegaly, and abdominal mass. Symptoms - low-grade fever, weight loss, night sweats, itching. Management includes radiation and chemotherapy, and survival rates are quite high. 2. Non-Hodgkin Lymphoma Generic term for a diverse group of lymphomas. Clinical manifestations of NHL: o Similar to Hodgkin lymphoma, but non-Hodgkin lymphoma progresses to include symptoms of the nasopharynx, gastrointestinal tract, bone, testes, and other soft tissues. o Tends to involve many peripheral nodes and extends into extranodal tissues. o Low-grade NHL is often associated with very slow disease progression and long survival times. o High-grade lymphomas (like those seen in AIDS) have a very poor prognosis. a. Burkitt Lymphoma o B-cell tumor. o Most common type of non-Hodgkin lymphoma in children. o Burkitt lymphoma is a very fast-growing tumor of the jaw and facial bones. o Epstein-Barr virus is associated with >90% of cases. b. Multiple Myeloma (MM) o B-cell cancer characterized by the proliferation of malignant plasma cells that infiltrate the bone marrow and aggregate into tumor masses throughout the skeletal system. o Malignant B-cells secrete
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