1 N5315 Advanced Pathophysiology Disorders of Leukocytes Quantitative Alterations of Leukocytes You will want to be familiar with the meaning of these basic terms. They are commonly used to describe abnormally high or low white blood cell counts. The ones which end in the suffixes -osis or -philia tend to refer to an elevated count. The suffix –penia refers to a low count. The beginning of the word is the cell type. For instance, Leuko refers to all white blood cells. Neutro refers to neutrophils. Make sure you are familiar with the terms and what causes them. • Leukocytosis refers to an increase in the number of total WBC. • Leukopenia is a decrease in the number of total WBC. • Neutrophilia is an elevated neutrophil count which is commonly seen in bacterial infections, inflammation and necrotic tissue. • Neutropenia is a decrease in the number of neutrophils and is commonly seen in liver disease, viral infections, and drugs. • Eosinophilia is an increase in the number of eosinophils and is commonly seen in allergic reactions and parasitic infections. • Eosinopenia is a decrease in the number of eosinophils and is seen with pancytopenia and steroid use. • Basophilia is an increase in the number of basophils and is seen with allergic reactions. • Monocytosis is an increase in the number of monocytes and is seen when someone is recovering from an infection or with a TB infection. • Monocytopenia is a decrease in the number of monocytes and can be seen with steroid use and HIV infection. • Lymphocytosis is an increase in the number of lymphocytes which is seen in viral infections, lymphoma and leukemia. • Lymphocytopenia is a decrease in the number of lymphocytes and is seen with AIDS, chemotherapy and steroid use. Leukemia Types2 Leukemia is a malignant disorder of the blood and blood forming organs. This results in an overproduction of leukocytes by the bone marrow. The overproduction causes an overcrowding in the bone marrow by the leukemic cells thus preventing the production of normal blood cells. These cells are ejected into the blood and accumulate in the liver, spleen, lymph nodes and other organs in the body. Leukemia may be classified as acute or chronic. Acute leukemias are abrupt in onset, are aggressive diseases and are characterized by the production and accumulation of immature cells such as blast cells. Chronic leukemias are characterized by the production of cells that appear mature but do not function appropriately and they accumulate. The onset of chronic leukemia is gradual in nature, and it is far less aggressive than acute leukemia. Leukemias may be classified as myelogenous versus lymphocytic. Myelogenous means that there is an excessive production of granulocytes, whereas in lymphocytic leukemias, the excessive production is with the lymphocytes. In all forms of leukemia, men tend to be more commonly affected as are Americans of European descent. Caucasian children are more commonly affected than other children. ALL is the least common type but is the most common type in children. CLL and AML are most common in adults. Make sure you are familiar with the various characteristics of the types of leukemias presented in this chart. Also review the table in your textbook titled: Clinical Manifestations and Related Physiology in Leukemia. Type Pathology Age of Onset Signs & Symptoms Prognosis Acute Lymphocytic Leukemia (ALL) Marked by > 30% of lymphoblasts in the blood or bone marrow. The proliferation of blast cells is related to genetic/chromosomal abnormalities. Most common in children but is seen in adults. Fever, pallor, bleeding, fatigue, lymphadenopathy, infection, joint pain, splenomegaly, hepatomegaly, night sweats, weight loss, anemia, thrombocytopenia, petechiae and ecchymosis. Survival rate decreases with age.3 CNS may be affected: headache, vomiting, papilledema, facial palsy, meningeal irritation. Acute Myelogenous Leukemia (AML) Is marked by a proliferation of immature myeloid cells, decreased apoptosis and a lack of cellular differentiation. There are many chromosomal abnormalities associated with the disorder. It is aggressive and fast growing. Most common adult leukemia. Incidence increases with age. As above Remission rates are inversely related to age. Chronic Lymphocytic Leukemia (CLL) Malignant transformation of B-lymphocytes. They do not prevent the growth of normal blood cells as much as an acute leukemia does. B-cells have decreased apoptosis. Infiltrates lymph nodes, liver, spleen and salivary glands. Incidence is increased in persons older than 40. Suppression of humoral immunity, increased infections with encapsulated bacteria. Most are asymptomatic at the time of diagnosis. Neutropenia Longer life span expected than in acute leukemias. Survival time is ten or more years.4 Chronic Myelogenous Leukemia (CML) Characterized by the presence of the Philadelphia chromosome Incidence is increased in persons older than 40. Splenomegaly most common finding. Hepatomegaly, hyperuricemia, infection, fever, wt loss Bone marrow transplant may be curative. Pathophysiology overview of leukemia: All leukemias share some of the same pathologic characteristics. Most leukemias arise from the B-cell and T-cell differentiation pathways. The majority of leukemias arise from the B-cell differentiation pathway. Leukemia blast cells are immature WBCs which fill the bone marrow and spill into the blood. They crowd out the bone marrow and trigger the cessation of the production of other blood cells. This leads to a pancytopenia. The Philadelphia chromosome is mainly located in CML but may be found in some persons with AML and ALL. This chromosome is a result of a translocation between chromosomes 9 and 22. The translocation causes a fusion of the BCR 1 gene region on chromosome 22 and the proto-oncogene ABL1 on chromosome 9. This results in the expression of an oncoprotein called the BCR-ABL1. This protein promotes cell proliferation, which is needed for cells to become leukemic cells. This protein not only increases cellular proliferation, but it decreases sensitivity to apoptosis. African Americans tend to have lower mortality rates than Caucasians from acute leukemias. Acute leukemias tend to run in families and show an increased incidence with other hereditary abnormalities such as Down’s Syndrome, Faconi
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