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267 Cards in this Set
- Front
- Back
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Neutrophils and Accute Inflammation
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What is an infection?
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The invasion of bacteria, viruses, fungi in tissues.
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What are the difinitive signs of inflammation?
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Redness and swelling with heat and pain. Virchow added loss of function.
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What causes the redness seen in inflammation?
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Dilation of blood vessels.
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What causes the heat seen in inflammation?
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Increased quantity of blood in the area.
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What causes the swelling seen in inflammation?
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Enlargement of the blood vessels.
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What causes the pain seen in inflammation?
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Pressure on nerve endings by the swollen tissue. Kinins also impact nerve endings.
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What is innate immunity?
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The mechanisms present at birth, usually non-specific.
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What is acquired immunity?
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Mechanisms specific to the foreign agent. Requires prior exposure to the agent for full expression.
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What are the mechanisms of innate immunity?
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Prevention of the entry of microorganisms and other noxious substances into the body by physical barriers to infection and chemical agents that are secreted.
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What secretion in the respiratory and GI tracts provides innate immunity?
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Mucus
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What cells are involved in providing innate immunity?
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Neutrophils and Natural Killer cells.
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What occurs if the innate immunity fails?
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Complement pathway activation and phagocytosis.
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What are the three important phagocytic cells?
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Neutrophils, Monocytes, and Macrophages
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What do neutrophils target? Describe them.
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Microbial invasions. Neutrophils are short-lived cells.
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What is the role of monocytes? Describe the cells.
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Monocytes remove certain microorganisms. They are used in the processing and presentation of antigens to T-cells.
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What is the role of macrophages? Describe the cells.
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Clears foreign particulate matter and destroys senescent or abnormal blood cells.
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What is pneumonia?
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Inflammation and consolidation of pulmonary parenchyma.
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What are the characteristics of acute inflammation?
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Rapid onset
Neutrophil dominance Prominent vascular response (pain and edema) Last for hours to weeks. |
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What are the characteristics of chronic inflammation?
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Slow response
Mononuclear cell dominance Duration of weeks to years |
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Describe the lifecycle of a leukocyte.
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Margination
Adhesion Emigration to chemotactic stimulus Phagocytosis and intracellular degradation Extracellular release of leukocyte products. |
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What are the proteins that a neutrophil uses to attach to the endothelial cells?
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P,L, and E-selection
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What is the other name for respiratory burst? What is it?
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Oxidative burst.
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When does respiratory burst occur?
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When leukocytes in an inflammed tissue come into contact with pathogenic organisms.
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What does the respiratory burst do?
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It degrades internalized particles and substances like bacteria after they have been consumed by phagocytic cells.
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Describe the generation of superoxide.
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2 O2 + NADPH --> 2 O2- + NADP+ + H+
Occurs in the presence of NADPH Oxidase |
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What occus to superoxide?
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Undergoes dismuatation to form hydrogen peroxide.
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What is the formula for dismutation?
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2 O2- + 2 H+ --> H2O2 + O2
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What is the fomula for the creation of hydroxyl radical? What is it used to destroy?
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H2O2 + O2 --> OH· + OH- + O2
It attacks DNA |
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What is the fomula for the creation of hypochlorous acid?
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H2O2 + Cl- --> HOCL + H2)
Occurs in the presense of myeloperoxidase |
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Vascular Phase of Acute Inflammation and the Complement System
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What is edema?
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A process in vascularized tissues where fluid and WBC's accumulate at the site of injury.
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What occus to blood vessels in response to tissue injury?
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Vascular dilation which inceases flow
Inceased vascular permeability with accumulation of fluid and plasma compoenents in the tissue |
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What occurs to vascular pressure in sites of inflammation?
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Osmotic pressure due to protein leakage decreases
Arteriole/venous pressure increases |
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What are the mechanisms by which vascular tissue becomes more permeabile in acute inflammation?
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Endothelial cells contract in reponse to chemical inflammatory mediators, creating transient gaps between cells, increasing permeability to plasma proteins. Direct injury to endothelial cells can also cause increased vascular permeability.
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What are the plasma derived vasoactive mediator sources? What are their respective vasoactive mediators?
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Hageman factor activation leads to activation of the clotting/fidinolytic system and the kallikrein-kinin system. Activation of the complement system leads to actiavtion of C3a and C5a mediators. These mediators both lead to increased vascular permeability and edema.
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What are the cell derived vasoactive mediator sources? What are their respective vasoactive mediators?
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Mast cell and basophil degranulation leads to histamine release.
Platets cause the release of serotonin Inflammatory cells release prostaglandins, lekotrienes, and platelet activating factor The endothelium release nitric oxide, prostaglandins, and platelet activating factor. |
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Where are the plasma derived vasoactive mediators come from?
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Derived from major protease cascades composed of sequentially activated zymogens.
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What is transudate?
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Edema fluid with low protein content and a specific gravity of less than 1.015.
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What is exudate?
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Edema fluid with high protein content and a specific gravity of greater than 1.015.
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What are the types of exudates? Describe them
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Serous - absense of prominent cellular component
Fibrinous 0- contains a large amount of fibrin from activation of coagulation Purulent - contains prominent cellular components (neutrophils). |
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What is suppurative inflammation?
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Infammation that releases purulent exudate with liquefactive necrosis (pus).
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What is meningitis?
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Inflammation of the meninges, the membranes that surround the spinal cord and brain.
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What causes meningitis?
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Bacteria, viruses, and fungi can cause it
Haemophlius influenzae B and Neisseria meningitidis are the most important bacteria. |
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What is the Complement System?
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A biochemical pathwya that is a key part of the innate immune system, though it also assist with adaptive immunity.
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How does the Complement System work?
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A series of blood proteins which, when activated, lead to lysis of cells that are labeled for destruction.
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What are the anaphylatoxins that increase vascular permeabilityas part of the Complement System?
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C3a, C4a, and C5a
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What is the element of the Complement system that is a chemoattractant?
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C5a
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What is opsonization? What increases this?
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Opsonization is the coating of a pathogen with molecules that enhance phagocytosis. C3b of Complement System increases this.
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What makes up the complex of the Complement System that causes a hole to form in the cell membrane of pathogens?
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C5-C9
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What are the three possible initial activation pathways of the Complement System? Describe them.
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The Alternative Pathway - pathogen surface creates local environment conducive to complement activation
The Lectin Pathway - mannose binding lectin binds to pathogen surface The Classical Pathway - C reactive protein or antibody binds to specific antigen on pathogen surface. |
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After the initial activation pathway of the Complement System completes, what happens?
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C3 is cleaved into C3a and C3b. C3b convalently binds to the surface components of the pathogen.
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What occurs after the cleavage of C3?
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Inflammatory cells are recruited
Pathogens are opsonized which facilitates their phagocytosis Pathogen cell membranes are perforated |
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What is the ligand that activates the Complement?
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IL-6 is release by macrophages that have attached bacteria. This causes the liver to rleease mannose-binding lectin and c-reactive protein.
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What does C-reactive protein bind to? What does this do?
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Phosphocholine on bacterial surfaces.
This binding acts as an opsonin and an Complement activator. |
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What does mannose-binding lectin bind to? What does this do?
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Binds to carbohydrates on bacterial surfaces.
This binding acts as an opsonin and an Complement activator. |
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Mononuclear Leukocytes and Chronic Inflammation
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Compare the characteristics of lifespan, type of inflammation, function, and cytokines, and radicals between neutrophils and monocytes/macrophages.
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Lifespan - Neutrophils live for a day while monocytes live for weeks to months
Inflammation - Neutrophils are involved in accute inflammation while monocytes are involved in chronic inflammation Function - neutrophils kill bacteria while monocytes have multiple functions Radicals - neutrophils use O2- while monocytes use O2- and nitric oxide (NO) |
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What are monocytes most closely related to? What stage of development are they? What is the difference between their nuclei?
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They are related to neutrophils.
They are intermediate-stage cells that can further develop into macrophages. Neutrophils have segmented nuclei while monocytes have singular nuclei. |
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What is the role of monocytes/macrophages?
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Defense by phagocytosis, but also initiates the immune system, recruits lymphocytes, activates fibroblasts, and induces new blood vessel formation.
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Where are developing macrophages first found during embryonic development?
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In the yold sac.
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Where are macrophages produced during hematopoiesis?
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The fetal liver.
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Whare type of monocytes are produced in adult bone marrow?
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Ly6C+ inflammatory monocytes which are recruited to tissue and develop into mature macrophages.
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How long does proliferation and maturation of monocytes take in bone marrow? How long do they stay in blood circulation?
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5 to 6 days.
2 to 3 days. |
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How are monocytes classified?
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Expression of CD14 and CD16.
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What happens once a monocyte enters a tissue? How long does it live?
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Undergoes blast formation and becomes an immature macrophage and the na mature macrophage (also called a histiocyte).
It can live for months to years. |
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What doe smonocytes replenish in the epidermis?
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Langerhans cells.
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What cells for osteoclasts in bone?
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Macrophage-CSF and RANKL mature to form osteoclasts.
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What transforms monocytes into alveolar macrophages?
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GM-CSF
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What determines the phenotype of a macrophage?
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The phenotype is determined by the mediator that attracts the monocyte.
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What is the hallmark cell of acute inflammation?
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Neutrophils
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What is the hallmark cell of chronic inflammation?
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Monocytes and lymphocytes
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What is the timeline of inflammation?
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Acute response takes place almost immediately with fluids and then neutrophils pouring out into the affected area. If the injury is not immediately removed, the chronic response takes over.
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What are the fours outcomes of inflammation?
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Complete resolution
Healing by scarring Abscess formation Progression to chronic inflammation. |
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What are the human chronic inflammatory disease that being without following acute inflammation?
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Rheumatoid arthirtis
Tuberculosis Chronic Lung Disease |
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What are some of the causes of Chronic Inflammation?
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Persistant infection by intracellular microorganisms
Prolonged exposure to non-degradable substances Immune reactions |
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What are some examples of non-degradable substances?
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Silica and asbestos which cause silicosis and asbestosis respectively.
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Describe the appearance of lymphocytes.
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Small, round, very darkly staining nuclei and very little surrounding cytoplasm.
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Descrbie the appearance of macrophages.
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Larger, plaer, oval or bean shaped nuclei and a somewhat larger amount of cytoplasm.
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Lymphocytes and the Immune System
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Where do B-cells differentiate? Where do the travel to?
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Differentiate in the bone marrow
Travel to lymphoid organs |
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Where do T-cells differentiate? Where do the travel to?
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Differentiate in the thymus
Travel to lymphoid organs |
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What do lymphoid stem cells become?
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T lymphocytes
B lymphocytes NK lymphocytes |
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What do myeloid stem cells become?
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Neutrophils
Monocytes/Macrophages Eosinophils Erythrocytes Megakaryocytes Basophils Mast Cells |
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What is the hallmark of the cells that are the progeny of lympohoid stem cells?
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They have very little cytoplasm.
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Where do T- and B-lymphocytes go through antigen-dependent development?
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Secondary lymphoid organs.
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What are the secondary lymphoid organs?
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Spleen, lymph nodes, mucosa-associated lymphoid tissue (trachea, tonsils, Peyer's patches and the appendix).
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What is the first step in the differentiation of B-lymphocyte stem cells?
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The genes of the immunoglobulin chain rearrange, permitting synthesis of IgM chains in the cytoplasm of the cell.
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What is the B-lymphocyte stem cell referred to after immunoglobulin light chain gene rearrangement?
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Virgin B-cells.
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What causes the final stage of development of B-lymphocyte stem cells?
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Stimulation by foreign antigenic presentation by an APC.
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What are the B-lymphocytes that release antibodies called?
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Plasma cells.
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After T-lymphocytes leave the thymus and travel to the peripheral lymphoid tissue, what must occur to continue developing?
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They must be activated by and antigen bearing APC.
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What occurs after APC activation of T-lymphocytes?
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A lymphoblast forms.
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What does a lymphoblast become?
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A prolymphocyte.
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What does a prolymphocyte become?
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An immature lymphocyte that is released into the bloodstream where it matures into an active T-cell.
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What are the CD4+ T-lymphocytes? Describe them.
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T-helper lymphocytes - induce activation of B-lymphocytes and secrete cytokines
T-delayed-type hypersensitivity - secrete chemotactic factors for macrophages |
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What causes T-helper lymphocytes to differentiate into the sub-classes?
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Cytokine signals.
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What is the primary cell partner of TH1 cells? TH2 cells?
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Macrophages
B-cells |
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What are the cytokines produced by TH1 cells? TH2 cells?
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IL-2, interferon gamma, tumor necrosis factor alpha
IL-2,4,5,6,10,13 |
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What is the immune stimulation promoted by TH1 cells? TH2 cells?
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Cellular immunity, maximizes cell killing by macrophages and boosts CD8+ T-cells
Humoral immunity, stimulates B-cells to proliferate, and increase antibody production. |
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What are the CD8+ T-lymphocytes? Describe them.
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Regulatory T-cells (Suppressor T-lymphocytes) - shut down T cell-mediated immunity toward the end of an immune response
Cytotoxic T-lymphocytes - release cytolytic substances which destroy virally infected cells and tumor cells, also implicated in transplant rejection. |
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What are the two subtypes of Memory T cells? What is their CD status?
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Central memory T cells and Effector memory T cells
They can be either CD4+ or CD8+ |
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What makes a Natural Killer cell unique?
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Spontaneously can kill tumor cells and virus infected cells producing large quantities of gamma interferon.
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When is the thymus most active? What is produced here?
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Active during fetal life when committeed lymphoid stem cells begin to differentiate
It is the site of T-lymphocyte differentiation. |
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What are the four functions of the spleen?
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Removal of senescent or antibody-coated RBCs.
Blood pooling that allows for dynamic equilibrium with the circulating pool. 5% of total RBC mass and 1/3 of platelet mass. Collection and concentraiton of blood-born foreign antigens for processing by the immune system. Hematopoietic during embryonic development. Reactivates during extreme conditions. |
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What is red pulp? What does it do?
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Mainly cords and sinuses in lymphoid tissue lined with macrophages.
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What is white pulp? What does it do?
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Lymphoid tissue with loosely packed lymphocytes that surrounds central arteries. Contains both B- and T-lymphocytes.
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What is the boundary between the white and red pulp called? What is it made up of?
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Called the marginal zone. It is rich in dendritic APCs that capture, process, and present antignes for T-cell stimulation.
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Acquired Immunity
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How does an MHC class 1 APC function?
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Short peptide or carbohydrate fragments from antigens are bound to MHC molecules and incorporated into the cell membrane. Cytotoxic CD8+ T cells pickup the presented antigen.
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What is the difference between MHC Class I and Class II APCs?
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If the antigen is from outside of the cell, it binds to MHC Class II APCs.
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Where are MHC Class I molecules found? MHC Class II?
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MHC Class I molecules are found in almost all nucleated cells while MHC Class II molecules ares only found in a limited number of cell types.
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What type of T-cell interacts with MHC Class I molecules? MCH Class II?
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CD8+ T-Cells interact with MHC Class I molecules
CD4+ T-Cells interact with MHC Class II molecules. |
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What are the three types of APCs?
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Monocytes/Macrophages
Dendritic Cells B-Cells |
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How are B-cells dependent on T-cells?
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T-cells produce growth factors (Interferon gamm, IL-2, and IL-3) for B-cells.
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What is P Vera?
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A neoplastic disorder arising from a PPSC. Erythorcytosis occurs with or without increases in platelets and WBCs.
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What is usually required for erythroid progenitor cells to divide? What is required in patients with P Vera?
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Erythropoietin (EPO)
Growth occurs without EPO. |
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What causes P Vera?
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JAK2 mutation induces constitutive activity of a RTK which causes unregulated sinaling and proliferation of erythrocytes.
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What are the symptoms of P Vera?
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All Erythrocytosis - headache, decreased mental acuity, generalized weakness
P Vera - Pruritus (itching), erythromelalgia (burning of extremeties), hypermetabolism, thrombosis, hemorrhage, splenomegaly, and heaptomegaly. |
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What are the lab findings for P Vera?
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Increased hemoglobin/hematocrit
50% increase in WBCs and platelets Basophilia Low EPO JAK2 mutation |
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What is the treatment for P Vera?
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Phlembotomy
Myelosuppresive agents Interferon alpha |
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What is Essential Thrombocythemia?
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Over production of platelets that can progress to myelofibrosis that is not a result of cancer, infection, inflammation, bleeding, or iron deficiency.
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What is the major complication of ET?
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Thrombosis
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What are the treatments for ET?
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Anagrelide
Hydroxurea**Interferon Alpha |
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What is myelofibrosis (MF)?
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Growth and proliferation of abnormal stem cell which replaces bone marrow with fibrous connective tissue.
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What are the symptoms of MF?
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Increased platelets and normal Hb and WBCs initially.
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What is myelodysplastic syndrome?
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Condition in which there is disordered maturation in 1 or more cell lines, producing cytopenias.
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What is a common progression of patients with MDS?
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Develop AML.
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What cell abnormalities are seen in patients with MDS?
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Genetic alterations.
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What is the treatment for MDS?
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Transfusions of RBCs and platelets
Growth factors Bone marrow transplantation |
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Leukocyte Disorders
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What is granulomatous inflammation?
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Occurs when a substance cannot be easily digested.
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What are the cell types involved in granulomatous inflammation?
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Macrophages and lymphocytes
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What occurs to macrophages when they reach the site of the undigestable material?
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They lose motility and transform into epithelioid cells.
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What is Chronic Granulomatous Disease (CGD)?
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Inherited disorder which prevents phagocytosis by inability to produce superoxide anions and thus causes life threatening bacterial and fungal infections. Chronic granulomas form in response to chronic inflammation.
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What causes CGD?
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Defect in NADPH oxidase
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CGD diagnosis should be considered in patients susceptible to which kinds of bacteria? Which specifically?
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Organisms that normal people can resist.
Catalase-positive organisms and Serratia marcescens. |
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What is tuberculosis (TB)?
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A common and deadly infectious disease caused by Mycobacterium tuberculosis that attacks the lungs.
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What is the treatment for TB?
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Extensive use of antibiotics.
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When is TB the most lethal?
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Patients with HIV.
It is the leading cause of death among people who are HIV+ |
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What cell type is common in patients with TB?
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Langhans-type giant cells formed from macrophages.
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What is sepsis?
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Infection of the bloodstream by a toxin-producing bacteria.
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What type of inflammatory response is seen in sepsis?
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Sequential generation of pro- and anti-inflammatory cytokines from leukocytes.
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What is Disseminate Intravascular Coagulation (DIC)?
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Increased coagulation, widespread thrombosis and hemorrhage. Often a fatal condition (Death Is Coming).
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What is leukocytosis?
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Increases in white cell number.
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What is neutrophilia? What causes it?
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Release of immature neturophils, also called a myeloid "left shift".
Bacterial infection. |
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What is lymphocytosis?
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Occurs during viral infections and rarely in bacterial infections, but it must be distinguished from CLL.
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What is mononucleosis?
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Epstein Barr Virus infects B-lymphocytes. The infected B-cells are killed by cytotoxic T-cells.
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Hematological Cancer
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What is hyperplasia/hypertrophy? What is it caused by?
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An increase in the number of cells associated with an increase in tissue mass (hypertrophy). Physiologic (thickening of foot soles) or pathologic (cancerous).
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What is metaplasia?
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An adaptive respones that is usually reversible. It is often related to things like smoking, but is not necessarially cancer.
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What is dysplasia?
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Atypical proliferation of cells. Cells have an abnormal appearance with variations in size and shape, nuclear enlargement, and dark staining of the nuclei. The can also be arranged in a disorderly manner. Can be a precursor of cancer.
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What is neoplasia?
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Abnormal growth of tissue that is uncoordinated and autonomous.
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What is a malignant neoplasm?
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Somatic cell mutants with deregulation of growth control genes. Show a variable degree of difference from normal counterparts. May disseminate through the lymph/blood.
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What is a benign neoplasm?
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Grows slowly and remains localized with no adverse effects on the host except by virtue of size. Closely related to normal tissue cells.
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What is a leukemia/lymphoma?
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Cancers arising from unregulated clonal proliferation of heamtopoietic stem cells that never stop dividing, crowding out and displacing normal hematopoietic tissue.
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What is acute leukemia?
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Results from the accumulation of early myeloid or lymphoid precursors in the bone marrow, blood and other tissues.
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How does acute leukemia present?
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Appears quickly (days to weeks)
Features of bone marrow death. |
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What is Acute Myeloid Leukemia?
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Neoplastic proliferation of defective myeloblasts, monoblasts, erythroblasts, or megakaryoblasts.
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What is Acute Leymphoblastic Leukemia?
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Primarially a disease of children and young adults.
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What is a chronic leukemia?
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A myelo- or lymphoproliferative disorder of PPSCs with an onset of months to years. Characterized by massive over production of normal appearing, but slightly defective granulocytes (myeloid) or immunologically indolent lymphocytes (lymphoid).
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What is a lymphoma?
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A solid malignant tumor of the lymphoreticular system.
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What is the difference between a lymphoma and a leukemia?
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Lymphomas arrise from primary or secondary lymphoid tissue and occasionally venture into the bloodstream while leukemias arise from the marrow and freely cross the marrow/blood barrier.
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What is multiple myeloma (MM)?
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B lymphoid malignancy with proliferation of malignant plasma cells.
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What do plasma cells from MM produce?
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Plasma cells produce excessive amounts of monoclonal immunoglobulin and self-serving cytokines which can suppress synthesis of normal antibodies, inhibit hematopoiesis, and corrode bone.
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What is the age pattern in the leukemias?
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ALL - 80% < 20 YO with at peak ~5 yo
AML - 20% < 20 YO with incidence rising with age CML - uncommon in children most seen in 25-70 YO with incidence rising with age. CLL - rarely seen in children 90% >50 YO |
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Acute Leukemia
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What is AML?
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Acute myeloid leukemia resulting from malignancy of a committee myeloid progenitor cell.
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What is the most common cell type seen in patients with AML?
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Myeloblasts
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What can cause AML?
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Prior radiation or chemotherapy
Benzene exposure MDS |
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What class of AML is dominated by myeloblasts?
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M0/M1
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What class of AML has Auer rods and myeloperoxidase activity and even number of myeloblasts and promyelocytes?
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M2
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What class of AML has Auer rods and promyelocytes?
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M3
Very common |
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What is the pathophysiology of AML?
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Hypermetabolic symptoms
Anemia Neutropenia |
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What is the prognosis if Auer rods are seen?
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Positive
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What is the prognosis if the FAB type is M5, M6, or M7?
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Negative
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What is the prognosis if there is a deletion of chromosome 5 or 7?
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Negative
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What is thre treatment of AML?
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Cytotoxic chemotherapy or bone marrow transplantation
Chemotherapy is the accepted management method. |
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What is the treatmetn of M3 AML or acute promyelocytic leukemia?
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Chemotherapy with daunorubicin and treatment with Arsenic trioxide and ATRA (all-trans retinoic acid)
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Where is the cell lineage mutation that causes ALL?
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In the committee lymphoid progenitor cell.
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What is the morphology seen in patients with ALL?
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Homogenous population of lymphoblasts.
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Where do the majority of pediatric cases of ALL begin?
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They begin with B-cell precursors in the bone marrow.
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What is the type of ALL if the cell is positive for CD10, CD19, or CD34?
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Precursor B-cell
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What is the type of ALL if the cell is negative for CD34 and positive for CD10, CD19, CD20, and CD22?
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Mature B-cell
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What is the type of ALL if the cell is positive for CD3, CD4, and CD8?
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Precursor T-cell
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Is the prognosis for ALL positive or negative if the Philadelphia Chromosome is present?
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Negative
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Is the prognosis for ALL positive or negative if the patient is between 3 and 7 YO?
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Positive
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Is the prognosis for ALL positive or negative if the pateint is black?
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Negative
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What is the most common FAB subtype?
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90% of childhood ALL is of the L1 subtype.
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What is the therapy for ALL?
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Kill leukemic cells quickly with combination chemotherapy.
Maintain long term remission with agents used for managing AML. |
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Chronic Leukemias
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Which is easier to treat with traditional chemotherapy, acute leukemia or chronic leukemia?
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Acute leukemia
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What cytogenetic feature is seen in CML?
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The Philadelphia chromosome t(9;22)
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What ar ethe common laboratory findings of CML?
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Leukocytosis, Basophilia
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What does the translocation in the Philadelphia Chromosome actually do?
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Creates a chimeric Bcr-Able gene that provides unregulated tyrosine kinase activity.
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What is acute transformation in CML?
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The transition between the chronic phase and blast cell crisis.
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What are the defining characteristics of the chronic phase of CML?
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Massive increase in the granulocyte count.
Splenomegaly Presenence of the Philadelphia chromosome |
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How can CML be cured?
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Bone marrow transplant.
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What new treatment was found for CML? What class of drug is it?
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Gleevec
Bcr-Abl Kinase Inhibitor that inhibits ATP binding site on the chimeric protein |
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When is Gleevec effective?
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During the chronic phase of CML, but not during the blast crisis of CML
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What can cause Gleevec to not function in patients still in the chronic phase of CML?
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Amplification/overexpression of Bcr-Abl.
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What is the origin of CLL?
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Malignancy of mature B-cells.
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What causes CLL?
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Expression of anti-apoptotic protein that prevents cell death of B-cells.
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What is the environmental cause of CLL?
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Agent Orange
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What common physical finding differentiates CLL from CML?
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Lymphadenopathy
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What occurs as the disease progresses?
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The patient is more susceptible to bacterial, viral, and fungal disease because of the lack of functional lymphocytes.
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What type of B-cells are usually found in CLL?
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CB5+ B cells or slg+ B cells
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What causes CLL to because a large cell lymphoma?
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Richter's Transformation
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What are the therapies for CLL?
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Rarely curable, but quality of life can be improved with cytotoxic drugs, corticosteriods, and body irradiation. Therapeutic monoclonal antibodies can also be used.
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What are the two types of monoclonal antibody therapy used to treat CLL? How do they work?
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Rituxan - antibody to CD20 surface marker found on B-cell.
Alemtuzumab - antibody to CD52 surface marker found on B-cell. |
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When is chemotherapy used to treat CLL?
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When symptoms (fever, night sweats, weight loss, lyphadenopathy, splenomagaly, lymphocytosis, increased bacterial infections) impact the quality of life heavily.
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Where type of special cell is seen in peripheral blood smears of CLL patients?
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Smudge cells.
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Lymphoma
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What are lymphomas?
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Solid malignant tuomrs of the lymphoreticular system.
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What are the two types of lymphoma? Describe them.
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Hodgkin's Lymphoma - presence of the Reed-Sternberg cell
Non-Hodgkin's Lymphoma - diverse B and T cell lymph node malignancies. |
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What are the grades of a tumor? What characterizes each?
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Low - well differentiated malignant cells
Intermediate - moderately differentiated High - poorly differentiated |
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What are the stage designations? Describe each.
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A - asymptomatic
B - symptomatic |
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What are the symptoms that mark a lymphoma as type B?
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One of the below:
Fever > 38° Drenching night sweats Unintentional weight loss of >10% body weight in 6 months or less. |
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Describe the stages of lymphoma.
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Stage 1 - single region with little to no symptoms
Stage 2 - located in two separate regions on one side of the diaphragm Stage 3 - cancer has spread to both sides of the diaphragm Stage 4 - spread to one or more major organs, possibly including the bone marrow or skin. |
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What are the surface proteins on the Reed-Sternberg cell?
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CD15 and CD30
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What is a common receptor lost in Hodgkin's Lymphoma?
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B cell receptor (Ig)
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How is HD treated?
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Radiation and chemotherapy
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What is the incidence of HD?
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Bimodal with a peak at 20-30 and 55
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What is the most common HD subtype?
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Nodular sclerosis
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What is the least common HD subtype?
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Lymphocyte-depleted
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What is the HD subtype with the best prognosis?
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Nodular sclerosis and lymphocyte-predominance
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How are early stage HD patients treated?
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Radiation or chemotherapy
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How are early late HD patients treated?
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Chemotherapy because of the spread of cells.
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What is the gold standard for HD treatment?
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ABVD (adriamycin, bleomyci, vinblastine, and dacarbazine)
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What are most NHLs derived from?
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B cells
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What lymphoma acts similarly to CLL?
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Small lymphocytic lymphoma
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What is the hallmark of follicular lymphoma?
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t(14;18) translocation
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What is the most common NHL?
|
Diffuse large cell lymphoma
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What causes Diffuse large cell lymphoma?
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Abnormal Bcl-6 expression
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What type of Burkitt's lymphoma is seen predominately in Africans? What is it associated with?
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Endemic
EBV |
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What type of Burkitt's lymphoma is seen predominately in Americans?
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Sporadic
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What is the chemotherapy regimen used in NHL?
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R-CHOP
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Multiple Myeloma
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What is multiple myeloma (MM)?
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B lymphoid malignancy with proliferation of malignant plasma cells.
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What are the motility characteristics of MM?
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Solid tumors that like to disseminate in metastatic clusters in bone marrow cavities.
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Where does MM originate? Where is it found?
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Originate in lymph nodes, but tumors first apper in bone marrow. Malignant plasma cells are usually not found in circulation.
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What is the demographic of patients with MM?
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Older black adults
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What are the results of MM?
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Pathologic fractures
Renal failure Immunosuppresion with recurring infections Bone marrow death |
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What are the immunoglobulins produced by plasma cells in MM?
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IgG
IgD IgA |
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What are the key diagnostic features of MM?
|
Monoclonal immunoglobulin
Proteinuria in urine > 3.0 g/dL of M-protein >10% clonal plasma cells in bone marrow |
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What happens to the protein/albumin ratio in patients with MM?
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It goes up.
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What are the characteristics of Stage 1 MM?
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Beta2M < 3.5 mg/L and albumin >= 3.5 g/dL
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What are the characteristics of Stage 2 MM?
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Beta2M < 3.5 mg/L and albumin < 3.5 g/dL
OR Beta2M 3.5 - 5.5 mg/L |
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What are the characteristics of Stage 3 MM?
|
Beta2M > 5.5 mg/L
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What are the pathophysiologies of MM?
|
Bone pain
Hypercalcemia Osteolysis Anemia Respiratory tract infections |
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What causes renal impairment in patients with MM?
|
Immunoglobulin light chains secreted by plasma cells are deposited in the renal tubules, forming calcified casts. The casts cause inflammation which can result in fibrosis and renal failure.
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What is myeloma kidney?
|
Light chain cast nephropathy
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What is amyloidosis?
|
Partially degraded immunoglobulin light chains accumulate and damage major organs.
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In patients with amyloidosis, what is the major organ that is most commonly damaged?
|
The heart is enlarged and hardened.
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What are the neurological complications of MM?
|
Nerve tissue compression by tumor masses
Mental confusion caused by hypercalcemia Peripheral neuropathy and carpel tunnel syndrome Spinal cord compression which causes sensory loss, incontinence, and paraplegia |
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|
How is spinal cord compression treated in patients with MM?
|
Decompression surgery and radiotherapy
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|
|
Describe IgG myeloma.
|
Slower tumor growth
Lower incidence of hypercalcemia and amyloid deposits Increased susceptibility to bacterial infection Most common |
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|
Describe IgA myeloma.
|
Hyperviscosity because of IgA polymerization
Hypercalcemnia Amyloid desposits Less common |
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|
Describe IgD myeloma.
|
Particularly malignant
Tumors in spleen, lymph nodes, and bone Renal failure Amyloid deposits Not common |
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|
Describe Bence Jones (BJ) myeloma.
|
Immunoglobulin light (lambda) chains are synthesized without heavy chains
Most rapid tumor growth Highest incedence of renal failure, hypercalcemia, and amyloidosis Not common |
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|
What is the progession of MM? At which stage is therapy started?
|
MGUS --> Smoldering MM --> MM
MM |
|
|
What are Rouleaux formations?
|
Stacks of RBCs due to the large amounts of immunoglobulins
|
|
|
What are the abnormal cells seen in bone marrow of patients with MM? Describe them.
|
Myeloma plasma cells - large, oval cells with roudn, eccentirc nucleus
Flaming Plasma Cells Mott Cells - appear like a bunch of grapes |
|
|
What is used in MM therpy?
|
Alkylating agents
Prednisone Radiotherapy Bone Marrow Transplantation (Less Common) |
|
|
What is Waldenstrom's Macroglubulinemia (WM)
|
Low grade-type lymphoma of mature B-cells.
Associated with monoclonal IgM |
|
|
What are the symptoms of WM?
|
Hyperviscosity caused by elevated IgM levels.
|
|
|
How can amyloidosis be detected?
|
Congo red stain and light microscopy
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