Pathophysiology ch11
Clinical finding of multiple Myeloma
Bone marrow plasmacytosis → plasmacytomas (plasma cell tumors in soft tissue) and Lytic bone lesions Serum M-protein spike or the presence of Bence Jones proteins in the urine Other Laboratory features Hypercalcemia, elevated erythrocyte sediment rate (ESR), signs of kidney failure.
Prophylactic therapy with allopurinol is used for?
Hyperuricemia
Increased proliferation or increased breakdown of purine secondary to leukemic cell death from chemotherapy.
Hyperuricemia.
Inability to produce specific antibodies and Abnormal activation of complement.
Hypogammaglobulinemia
All myeloid cells affected resulting in anemia, thrombocytopenia, and agranulocytosis
aplastic anemia
disease of older adults but also seen in children and young adults.
AML: Acute myelocytic leukemia (AML)
Use the predominant white blood cell type and classification of acute or chronic to describe the four general types of leukemia.
Acute lymphocytic leukemia (ALL) - most common among children and adolescents Chronic lymphocytic leukemia (CLL): 1/3 of all Leukemias and is mainly a disorder of older persons, Malignancy of B lymphocytes. There are 2 types. 2 Types based on the aggressiveness of the disease and immunoglobulin variable (V) gene mutation Acute myelocytic leukemia (AML): Chronic myelocytic leukemia (CML): Excessive proliferation of marrow granulocytes, erythroid precursors, and megakaryocytes and Harbor the Philadelphia Chromosome abnormalit
This Leukemias most common form among children
Acute lymphocytic leukemia: ALL
List the three types of white blood cells and briefly describe their function.
Agranulocytes are divided into 2 different parts: lymphocytes and monocytes/macrophages. Lymphocytes: make up 30% of leukocytes. They originate in bone marrow and migrate through peripheral lymphoid organs where they recognize antigens and participate in immune responses. Monocytes/macrophages: make up 3-8% of leukocytes. They travel from bone marrow to body tissue where they differentiate into various phagocytes.
What drgus is use for Hyperuricemia?
Alopurinol
A patient have a Hallmark - presence of the BCR-ABL gene product detected in the peripheral blood. What disease does this patient have?
Chronic lymphocytic leukemia (CLL)
Excessive proliferation of marrow granulocytes, erythroid precursors, and megakaryocytes and Harbor the Philadelphia Chromosome abnormality.
Chronic myeloid leukemia (CML)
Harbor the Philadelphia Chromosome abnormality and Lymphadenopathy uncommon are the present of what disease?
Chronic myeloid leukemia (CML)
What does the Lymphoid Tissue Consist of?
Consist of lymphatic vessels, lymphoid tissue and lymph nodes, thymus, and spleen
Describe the mechanism of symptom production in neutropenia.
Depends on the severity, Place patient at risk for infections and skin lesions and ulcerative necrotizing lesions of the mouth most common
Cite two general causes of neutropenia.
Describe the mechanism of symptom production in neutropenia.
What is Used to diagnosed Infectious Mononucleosis?
EBV genome enters circulation and produce hetrophil antibodies
Example of Auto immune diseases
Felty syndrome a variant of rheumatoid arthritis
What are B-cell zones?
Follicles
What is Hematopoietic Growth Factors (recombinant human G-CSF) use for?
Increase white blood cells production
Describe the pathogenesis, clinical manifestations of infectious mononucleosis.
Incubation period from exposure to onset of symptoms - 4 to 8 weeks. Prodromal period - last several days - malaise, anorexia, and chills May have abrupt high fever Day 5 to 7 - pharyngitis and lymph node enlargement
Define infectious mononucleosis and describe the pathogenesis, clinical manifestations, and treatment.
Infectious mononucleosis (AKA; Kissing disease) is a Self-limiting lymphoproliferative disorder caused by the Epstein Barr virus (EBV) - a member of the herpesvirus family. Can occur at all ages - more in adolescents and young adults and Spread person to person through contact with infected oral secretions Proliferation of EBV is controlled by CD8 cytotoxic T cells and NK cells and T-cells appear large - increase node size.
Decrease in the absolute number of leukocytes in the blood Can affect any of the WBCs
Leukopenia
Explain the manifestations of leukemia in terms of altered cell differentiation.
Lymphocytic leukemia affects your lymph cells which includes, NK cells, T-cells, B-cells and plasma cells. Myelogenous leukemias which includes, Monocyte, Granulocyte: Neutrophil, Eosinophil, and Basophil, Platelets
Use the concepts regarding the central and peripheral lymphoid tissues to describe the site of origin of the malignant lymphomas, leukemias, and plasma cell dyscrasias.
Lymphocytic leukemias: Immature lymphocytes and their progenitors that infiltrate the spleen, lymph nodes, CNS, and other tissues. Myelogenous leukemias Involve the pluripotent myeloid stem cells in bone marrow- interfere with the maturation of all blood cells, including the granulocytes, erythrocytes, and thrombocytes. Plasma cell dyscrasias:
Lymphocytic versus myelogenous
Lymphocytic: Nuetophil, eosinophil,
Manifestations of multiple Myeloma
Main sites of involvement - bones and bone marrow Bone pain - one of the first symptoms
Describe the following complications of acute leukemia and its treatment
Most common form among children. Abrupt onset of symptoms Fatigue resulting from anemia Low-grade fever, night sweats, and weight loss due to the rapid proliferation and hypermetabolism of the leukemic cells Bleeding due to a decreased platelet count Bone pain and tenderness due to bone marrow expansion. Infection results from neutropenia - risk of infection Treatments options are: Chemotherapy Bone marrow and stem cell transplantation Not recommended in patients older than 50 to 55 years of age
List the three subtypes of granulocytes and briefly describe their role.
Neutrophils: make up 60-65% of leukocytes. They maintain normal host defenses against invading bacteria nad fungi cell debris, and a variety of foreign substances. Eosinophils: make up 1-3% of leukocytes. They are a part of 2 reactions. Allergic reactions: they release enzymes or chemical mediators that detoxify agents associated with the reaction. Parasitic infections: Basophils: make up .3-.5% of leukocytes. They contain heparin, an anticoagulant; and histamine, a vasodilator, and other mediators of inflammation.
What are T-cell zones?
Paracortex - contain most of the T-cells
List the three types of cells of the hematopoietic system.
Pluripotent stem cells Multipotent stem cells Committed progenitor cells
Relate the clonal expansion of immunoglobulin-producing plasma cells and accompanying destructive skeletal changes that occur with multiple myeloma.
Proliferation of malignant plasma cells in the bone marrow and osteolytic bone lesions throughout the skeletal system. Induces angiogenesis - Proteins increase blood viscosity Suppresses cell-mediated immunity - Immune depression Develops paracrine signaling loops - Infiltrate organs Unregulated production of abnormal monoclonal paraprotein - M protein - secreted in the urine - Bence Jones Protein Produce abnormal antibodies Proliferation of osteoclasts
Increase viscosity causes?
Pulmonary vessel occlusion - shortness of breath and dyspnea Cerebral leukostasis - diffuse headache and lethargy that progresses to confusion and coma
Describe the pathogenesis, treatment nfectious mononucleosis
Symptomatic and supportive. Bed rest, analgesics (acetaminophen, NSAIDS) to relieve pain, fever, headache and sore throat. Also, most people recover without incidence.
Trace the development of the different blood cells from their origin in the pluripotent bone marrow stem cell to their circulation in the bloodstream.
The Pluripotent stem cell gives rise to the lymphoid stem cell and the myeloid stem cell. These both differentiate into different cells. The Lymphoid stem cell differentiates into T cells, B cells, and natural killer (NK) cells. B cells turn into plasma cells. Meanwhile, myeloid stem cells differentiate into monocytes, granulocytes, megakaryocytes, and erythrocytes. Monocytes turn into monoblasts. Granulocytes turn into eosinophils, neutrophils, and basophils. Megakaryocytes turn into platelets. Erythrocytes turn into reticulocytes. This is what circulates in the blood stream.
Contrast and compare the signs and symptoms of Hodgkin lymphoma and non-Hodgkin lymphoma.
The first sign of the disease is often the appearance of enlarged lymph nodes. The two forms of lymphoma are marked by a painless swelling of the lymph nodes. Weight loss Fatigue and anemia - indicative of spread Hodgkin lymphomas are more likely to arise in the upper portion of the body (the neck, underarms, or chest). Non-Hodgkin lymphoma can arise in lymph nodes throughout the body, but can also arise in normal organs. Arise in T and B cells Non-Hodgkin lymphoma, by contrast, can be derived from B cells or T cells. And Hodgkin lymphoma can be derived from the B cells. None-Hodgkin Lymphoma: Spreads unpredictable fashion and None-Hodgkin Lymphoma Hodgkin Lymphoma: Reed Sternberg cell tumor marker Hodgkin Lymphoma: Arise in a single node or chain of nodes and spreads to the next node in a fashionable manner
What are treatments for multiple Myeloma
Treatment (rapidly changing) Front line therapy - High-dose chemotherapy with autologous stem cell transplantation
Describe the treatment measures used in Hodgkin disease and non-Hodgkin lymphoma.
Treatments:Localized radiation Combination - radiation and chemotherapy
Immature cells
blast crisis
A marked decrease in the number of granulocytes cells
granulocytopenia
Elevated circulating blast count (usually 100,000 cells/μL) Increases blood viscosity
leukostasis
Describe the role of the lymphoid tissues.
lymphocyte production for immune response. Lymphoid tissue makes up the lymph nodes, thymus, spleen, and bone marrow. In the lymph nodes, lymphoid tissue makes up fibrous capsules and radiating trabeculae which provides a supporting structure, and a delicate reticular network contributes to internal support.
Abnormally low number of neutrophils - less that 1500/μL Benign ethnic neutropenia. Seen in African descent and other Middle East ethnics - without predisposition to infections And Role of gene encoding the Duffy antigen receptor for chemokines - Provides protection from malaria.
neutropenia