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174 Cards in this Set
- Front
- Back
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What are the two system that works to help the body avoid injury? |
Innate Adaptive |
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What are the cells of the innate immune system? |
NEUTROPHILS MARCOPHAGES DENDRITIC CELL NATURAL KILLER NK CELLS |
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When CD4+(aka T helper cell) is presented with the MHC 11/antigen complex, 3 things occur? |
1. Memory T cells are made 2. Cytokines are released by CD4+ cells that activate B cells to become plasma cells , which will produce antibodies 3. Cytokines are released by CD4+ cells to recruit cytotoxic CD8+ T cells |
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What is pathophysiology? |
Involves the study of functional or physiologic changes in the body that results from disease processes. |
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Atrophy is |
Reduction in cell size |
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Hypertrophy is |
Increase in cell size |
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Hyperplasia is |
Increase in cell number |
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Metaplasia is |
Change in cell type |
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Dysplasia is |
Disorganized cell growth (cancer) |
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Pathologic calcification is |
Abnormal deposits of calcium salts in Tissue |
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Which are the 3 ways cells and tissue are damaged? |
Free radicals formation Hypoxia Impaired calcium homeostasis |
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Free radicals is |
Unstable highly reactive chemicals with unpaired electron in outer shell. |
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True or false: mechanism exist to neutralize ROS |
True |
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What happens when ROS exceeds the body's ability to neutralize them, it is termed ? |
Oxidative stress |
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Too much ROS can cause ? |
1.Oxidation (damage) of cellular components 2.Changes in gene expression and protein synthesis 3.Activation of signal transduction pathways |
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In hypoxic cell injury, cell is deprived of |
O2 (OXYGENATION) |
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Hypoxia can be due to: |
Inadequate O2 the the air Respiratory disease Ischemia Anemia (small amount of RBC) Edema ( swollen or excess water to an area) inability to the cells to use oxygen |
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When there is no oxygen the cells turns from aerobic metabolism to ? |
Anaerobic metabolism |
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What happens when anaerobic respiration is presented? |
Glycolysis occurs Fermentation instead of the Krebs cycle Alcohol will breakdown Lattice acid will breakdown Get only 2 ATP per glucose |
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What happens when aerobic respiration is presented? |
Glycolysis occurs We go through the Kerb cycle which occurs in the mirochondria There is a electrons transport which yields 36 ATP per glucose |
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True or false: Hypoxia leads to reduce ATP because it makes metabolism convert to anaerobic metabolism. It will yield a net lower of ATP. |
True |
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If you have less ATP to function or available. What will fail? |
Sodium (Na+)/ Potassium (K+) pump will fail |
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During impaired calcium homeostasis, calcium can __________ enzymes? |
Activate |
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What are the 5 board categories that causes cellular injury? |
Physical agents Radiation Chemicals Biological Nutritional imbalances |
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What happens when cells are injured? |
Reversible cell injury: cell swelling and fatty changes
Irreversible injury: apoptosis (programmed cell death) and necrosis cell (death of tissue) |
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Apoptosis is a __________ elimination of aged and injured cells |
Normal |
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TRUE OR FALSE: Apoptosis is regulated with out triggering the immune response because nothing will leak |
True |
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True or False: Necrosis is unregulated and it will leak out |
True |
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What are the 3 path of necrosis? |
Liquefaction Coagulation Caseation |
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Dry gangrene |
Tissue dry , shrinks, color changes to brown or black |
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Moist/wet gangrene |
Area is cold swollen and pulseless. Skin is moist black and under tension. |
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Gas gangrene |
Common in trauma and compound fractures in which dirt has become emdedded |
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The 5 cardinal signs of inflammation are? |
Redness Swelling Heat Pain Loss of function Systemic signs fever , fatigue occurs when inflammatory mediators enter circulation |
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What are the types of inflammation? |
Acute - early and short term Chronic - late and longterm |
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What does endothelium do? |
Maintain patency Release chemicals to dilate / constrict blood vessel Control migration Of nuetrophils |
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Histamine |
First mediators released Dilation Vascular permeability |
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Differentiate between atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia- including the mechanisms and causes of each |
Atrophy: Mechanism: 1.Reduced protein synthesis 2. Proteolysis(ubiquitin-proteasome system 3. Apoptosis Hypertrophy: increase in cell size and increase in amount of functioning tissue due to increase in workload (i.e. weight lifting) Mechanism: 1. ATP depletion 2.Mechanical forces -stretching 3.Activation of cell degradation products 4. Hormones -growth factors such as insulin Hyperplasia: increase in the number of cells in organ or tissue. (i.e. warts) Mechanism: Occurs in response to a stimulus and should stop when the stimulus has been removed Metaplasia: A change in which one adult cell type is replaced by another cell type (reversible) (i.e. "?replacement of cells in trachea in smokers) Mechanism: believed to be due to reprogramming of undifferentiated stem cells Dysplasia: Deranged cell growth. Results in cells of various sizes, shapes, and levels of organizations. (i.e. precancerous cells in the cervix) Mechanism: Chronic irritation and inflammation |
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Differentiate between dystrophic and metastatic calcifications, and give an example of each
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Dystrophic - deposits in dead tissue (Calcium phosphate derived from dying cells) Metastatic - deposits in functional tissue (Due to increased serum calcium levels Hyperparathyroidism, Renal failure, Mobilization of calcium from bone) |
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Describe the 3 major mechanisms by which cells are injured
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Free radical formation/reactive oxygen speciesHypoxia leading to ATP depletion
Impaired calcium homeostasis |
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Describe "free radical" and "reactive oxygen species", including how they are produced and whether they are normal or abnormal products of metabolism
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Unstable, highly reactive chemicals with unpaired electron in outer shell
- Hydroxyl radical (·OH) - Superoxide (O2-) • React with nearby molecules- Reactions cause unstable cell membranes, inactivate enzymes, and damage nucleic acids • Can cause chain events creating more free radicals |
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Describe the damage that can be caused by reactive oxygen species
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Exogenous triggers (UV & ionizing radiation) ROS production → generation of ROS exceeds the ability of the body to neutralize and eliminate ROS → Oxidative Stress → oxidations of cell components, activation of signal transduction pathways, and changes gene and protein expression → modifies DNA!!
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Name 3 conditions associated with reactive oxygen species
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Amyotrophic Lateral Sclerosis (ALS)
Cancer Cardiovascular Disease |
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Describe the mechanism behind hypoxic cell injury
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hypoxic cell injury leads to the body reverting to anaerobic respirations which causes the production of 2 ATP. This leads to the byproduct accumulation of lactic acid ultimately lowering the ph of the body. This altered state of ph can cause chromatin clumping, alterations to cellular membrane and cellular shrinkage. After anaerobic respirations is induced the body reverts to ATP depletion which it will under go a failure in its sodium potassium pumps. The intracellular concentrations of sodium will increase causing the retention of water and swelling of cells eventually leading to lysis.
Can be due to: Inadequate O₂ in the air Respiratory disease Ischemia Anemia Edema Inability of the cells to use oxygen |
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Describe the harmful effects of calcium within the cell
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Calcium can activate enzymes within the cell causing:
Phospholipases: Damage cell membrane Porteases: Damage cytoskeleton and membrane proteins ATPases: Breakdown ATP |
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Describe how temperature changes cause damage
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Moderate temps: vascular injury, increased cell metabolism, enzyme inactivation, cell membrane rupture
High temps: coagulation of blood and tissue protein Low temps: increases blood viscosity and causes vasoconstriction, leads to ischemia and hypoxia Freezing temps: ice crystals, vasoconstriction, coagulation in capillaries, edema from increased capillary permeability |
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Discuss the function of the immune system.
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To monitor, recognize, respond to and cease immune activity. The immune system monitors the body's internal environment for the presence of any pathogen or any changes in cells that may result in tumor formation. Help the body repair/fight off infectious diseases.
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Compare and contrast the innate and adaptive immune response.
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Innate: you are born with it. It includes certain physical, cellular, and chemical barriers throughout the body. It NONSPECIFIC
Active: Acquired immunity that develops in response to antigens. It is SPECIFIC to the antigen. Specificity is determined by B-cells and T-cells. |
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Describe the 3 major mechanisms by which cells are injured
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1.Free radical formation/reactive oxygen species
2.Hypoxia leading to ATP depletion 3.Impaired calcium homeostasis |
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Describe "free radical" and "reactive oxygen species", including how they are produced and whether they are normal or abnormal products of metabolism
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Free radicals: unstable, highly reactive chemicals with unpaired electrons in the outer shell. (abnormal products of metabolism.)
Reactive oxygen species: (ROS) include free radicals, and NON radicals. (normal products of metabolism) |
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Describe the damage that can be caused by reactive oxygen species
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ROS damage can cause:
Oxidation of cellular components Changes in gene expression and protein synthesis Activation of signal transduction pathways |
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Name 3 conditions associated with reactive oxygen species
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1. Amyotrophic Lateral Sclerosis (ALS)
2. Cancer 3. Cardiovascular Disease |
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Describe "antioxidant" and how they work
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Antioxidant: Inhibits the reaction of reactive oxygen species (ROS).
Types: Enzymatic: Super oxidedismutase, catalase → breaks-down reaction that forms water from hydrogen peroxide Non-enzymatic: Carotenes (Vitamin A), ascorbate (Vitamin C) Glutathione, flavonoids, selenium & zinc Function: They inhibit the reactions of ROS |
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Describe the harmful effects of calcium within the cell
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Calcium acts a messenger and signal for intracellular responses (Normal intracellular Ca is low)Ischemia and toxins can increase the Ca throughIntracellular influx across the membrane
Release of calcium from storage in mitochondria and SER Calcium can activate enzymes within the cellPhospholipase: damage cell membrane Proteases: damage cytoskeleton and membrane proteins ATPases: breakdown ATP |
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Describe how electricity injures cells, including the type of electricity most likely to cause injury, the portions of the body most affected, and the result of electrical injury
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Electrical Injury: results in tissue injury and disruption of electrical currents (nerves, heart)
Voltage: AC more dangerous than DC Amperage: pathway of current from entrance to exit is critical, currents pass through way of least resistance.Most tissue damage is caused by heat |
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Describe how radiation injures cells, including the type of radiation most likely to cause damage to the mechanism behind cell damage
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Radiation damages tissue by:
Interference with cell replication Genetic mutationImmediate cell death Affects cells with greater rates of mitosis Prolonged exposure can cause many types of cancerIonizing: ionizes atoms and molecules in cells (most likely to cause damage) UV(Ultraviolet): damage caused by reactive O2 species, and damage to DNA Non-ionizing: damage caused by vibration and rotation of atoms and molecules (least likely) |
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Name 3 types of chemical that can cause cellular damage, including the mechanism
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Lead: absorbed through gut, or lungs and stored in bone
Mercury: toxicity affects the CNS and kidneys Biological agents: viruses enter cells, incorporate into DNA, and replicate Nutritional imbalances: deficient in vitamins and minerals |
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Describe the 4 theories of cellular aging
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Evolutionary theory:Explains aging as a consequence of natural selection, in which traits that maximize the reproductive capacity of an individual are selected over those that maximize longevity
Molecular theory: Explain aging as a result of changes in gene expression Cellular theory: Explain cellular senescence in relation to telomere length or molecular events, free-radical damage, accumulated wear and tear, or apoptosis Systems theory:Attribute cellular aging to a decline in the integrative functions of organ systems such as the neuroendocrine and immunologic systems |
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Describe apoptosis, including whether it is a normal or abnormal process, the mechanism behind it, the cellular changes seen, and 2 examples of it
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Apoptosis: Normal process, number of cells is regulated by balancing cell proliferation
Cell changes associated:Shrinking and condensing of nucleus and cytoplasm Aggregation of chromatin DNA fragmentation Cell fragments into many, smaller bodies -Integrity of plasma membrane maintained- no inflammation! Changes in cell membrane induces phagocytosis by macrophages Examples* Embryonic development- during organ development and separation of webbed fingers and toesImmune system- control of cell numbers Cell cycle- removed of aged RBCs and cells in the intestine |
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Differentiate necrosis from apoptosis
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apoptosis is regulated and provided for cell death WITHOUT triggering the inflammatory response (no inflammation)
Necrosis is NOT regulated and results in inflammation. |
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Describe the 3 main types of necrosis, and provide an example of each
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Liquefaction: cell and/or tissue becomes liquefied
Coagulation: conversion into a grey, firm mass (i.e. myocardial infarction) Caseation: conversion into a "cheesy"substance by infiltration of fats (i.e. TB) |
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Differentiate the 3 types of gangrene
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Dry gangrene: tissue is dry and shrinks, color changes to brown or black (slow spread)
Moist gangrene: area is cold, swollen, and pulseless, skin is moist, black, and under tension (rapid spread) Gas gangrene: common in trauma and compound fractures in which dirt has become embedded, bubbles of hydrogen sulfide in muscle |
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Differentiate between innate and adaptive immunity, providing examples of each
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Innate: Physical barriers; skin, mucous membrane, saliva, urine, tears
Adaptive: Antibodies Both work to help the body avoid injury Innate Time of response: Immediate/fast & early responders Diversity: Limited to classes or group of microbes Microbe recognition:General patters on microbes; nonspecific Non-self recognition:yes Response to repeated infection: Similar with each response Defense: Epithelium, phagocytes, inflammation, fever Cellular Components: Phagocytes (monocytes/macrophages, neutrophils), NK cells and DCs Molecular components:Cytokines, complement proteins, acute-phase proteins, soluble mediators Examples:Skin, hair, mucous, phagocytes, granulocytes, trauma Adaptive Immunity Dependent upon exposure(first , delayed second, immediate due to production of antibodies Very large; specific for each unique antigen Specific to individual microbes and antigens (antigen/antibody complexes) yes Immunologic memory; more rapid and efficient with subsequent exposure Cell killing tagging of antigen by antibody for removal T & B lymphocytes, macrophages, DCs, NK cellsAntibodies, cytokines, complement system Pus, swelling, pain, T and B lymphocyte response |
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Describe components of the immune system
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Physical barriers: skin and mucous membranesCells of innate immune system: neutrophils, macrophages, dendritic cells, natural killer cellsPathogen recognition: PPR's, TLR's recognize PAMP's present on the surface of pathogens; stimulate cytokines that results in phagocytosis, and recruitment of other inflammatory cells
Soluble mediators: Opsonins: bind to microbe activates phagocytic cells Complement system: Series of inactive plasma proteins; when activated Stimulates opsonization of pathogens Recruits neutrophils and other cells for phagocytosis Stimulates release of histamine and other inflammatory mediators |
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Describe the process of antigen recognition for leukocytes and lymphocytes, including the role of APCs, MHC, CD4 cells and CD8 cells
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Simple explanation: Lymphocytes: Primary cells of adaptive immune system most abundant (30% of leukocytes)
B lymphocytes: when activated, differentiate into plasma cells and make antibodies T lymphocytes: several types T-helper cells (CD4): when activated by antigen presenting cells (APC's), regulate adaptive immune system and create memory Cytotoxic T-cells (CD8): when activated by antigen presenting cells, release reactive oxygen species to destroy infected cells *APCs: Engulf pathogen, break it down, bind a fragment to MHC II and present to T-cells for recognition When CD4+ (T “helper” Cell) is presented with the MHC II/antigen complex, 3 things occur: Memory T Cells are made Cytokines are released by CD4+ cells that activate B Cells to become plasma cells, which will produce antibodies Cytokines are released by CD4+ cells to recruit “cytotoxic” CD8 T Cells Recruited CD8+ cells bind to MHC I/pathogen complex of infected cell, release enzymes/cytokines, and destroy the infected cell Major Histocompatibility complex (MHC): genes that encode for HLAs:MHC I: activates CD8 cellsMHC II: activates CD4 cells |
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Describe how cells respond to antigen presentation
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Create a memory T Cell
Secrete cytokines that convert B cells into plasma cells Secrete cytokines that activate cytotoxic T-CellsMore memory!! |
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Differentiate cytokines, chemokines, and complement
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Cytokines: are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis.
Chemokines: any of a class of cytokines with functions that include attracting white blood cells to sites of infection Complement: Complement-dependent cytotoxicity is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell, the classical complement pathway is triggered by bonding protein C1q to these antibodies, resulting in formation of a membrane attack complex and target cell lysis. |
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Differentiate between primary and secondary humoral immune response
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Primary Humoral Response
First exposure to an antigen Slow to develop Results in memory cells Secondary Humoral Immune Response Subsequent exposure to the antigen Much quicker response-- because memory cells already created |
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Name and differentiate between the types of antibodies
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IgG: most abundant (75%)
Only one that crosses placenta-----> immunity to the fetus Rise slower but last longer Binds to infected and immune cells (macrophages, NK cells) and promotes lysis of infected cells IgA: common in mucous membranes and secretions and provides local immunity IgM: first to appear in response to antigen Promote agglutination of organisms for lysis or phagocytosis Rises quickly in acute infections IgD: on B cells - required for maturation IgE: inflammation, allergic responses, and parasites Binds to Fc receptors on mast cells releasing histamine |
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Describe the 3 responses to antigen
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Body exposed to antigen and develops ITS OWN immunity
Immune system of the host responds by creating antibodies to the antigen (may be a vaccine) Passive immunity: Immunity from another (i.e. chicken pox) |
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Differentiate between the 4 hypersensitivity reactions and give an example of each
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excessive or inappropriate activation of immune system
Type I IgE-mediated: Rapid allergic reaction; localized (atopic) localized edema and vasodilation (food allergy), systemic (anaphylaxis) widespread edema, vasodilation Type II antibody-mediated: Mediated by IgG or IgM directed against target antigens. Antibody binding to cell-surface antigen or complement causes cell destruction. Antibody on cell surface stimulates inflammation (i.e. glomerulonephritis) Antibody binding to cell receptor activates cell (Graves disease) Type III immune complex-mediated: Antigen/antibody complexes formed in the bloodstream. Complexes eventually are deposited in vascular epithelium or extravascular tissue. The location of the deposited antigen-antibody complex defines the response. Type IV T cell-mediated:Sensitized T lymphocytes. Rapid recruitment and activation of memory T-cells. (i.e. contact dermatitis; poison ivy, nickel, etc.) |
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Differentiate between acute and chronic organ rejection
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Acute organ rejection: Immediate, within days, signs of organ failure are evident
Chronic organ rejection:Delayed, immune-mediated inflammatory response, gradual failure of organ |
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Describe how graft vs. host disease is different from transplant rejection
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Graft vs host disease: Cells with functional immune capacity are transplanted into someone who is immunocompromised. The graded tissue rejects the host
Transplant Rejection: process in which a transplant recipient's immune system attacks the transplanted organ or tissue. |
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Describe the mechanism behind autoimmune disease
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The ability of the immune system to differentiate self from non-self. The body is unable to create an immune reaction against self-antigens.
Tolerance fails. Heredity, Gender, Environment: factors linked to autoimmune disease |
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Describe the mechanism behind lupus
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Due to B cell hyperactivity and increased production of autoantibodies. Trigger believed to be UV light, chemicals (hair dyes, drugs, foods or infectious agents viruses)
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Describe cell changes that occur with atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia, and state general conditions under which the changes occur.
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-Shrinking of the cell caused by factors that reduce the demand or adverse environmental conditions. Cells adapt to reduced demand by gradually shutting down their specialized functions. Decrease protein synthesis and increase protein degradation. Cells revert to low level of activity that sustains only basic needs of the cell.
-Process of cell enlargement that occurs in response to increased demands and/ or hormone signaling. Can be a pathologic process. Enlargement is from increased protein synthesis. Involves increase in functional components of the cell. Cell makes more enzymes and ATP to increase the functional capacity of the cell. -New cells formed by mitosis in response to a stimulus. Frequently occurs in conjunction with hypertrophy. Can only occur in tissues that contain cells capable of performing mitosis. Neurons and cardiac myocytes cannot regenerate. Can be physiological or pathologic. -Conversion of one cell type to another type. Change from one type of cell to a more resistant type resulting from chronic irritation or inflammation. Does not result from change in already differentiated cell type-results from "reprogramming" of stem cells (undifferentiated cell). Cell type stays within the boundary of the original tissue type. Usually, reduced function of the cell and increased propensity to form neoplasia.-Cells are disorganized and variable in size and shape (pleomorphic cells). Seen in severe, chronic irritation; usually epithelial. High mitotic rate. Large nuclei. Can be reversible, but less so than metaplasia. May precede tumors-precancerous. Can range from low grade (exhibits minimal cellular difference) to high grade (atypical and appears as neoplastic). High grade is considered to be in situ lesions-cancers that are still in place Simplified* -Atrophy: decrease in cell size -Hypertrophy: increased in cell size -Hyperplasia: increase in the number of cells in an organ or tissue -Metaplasia: reversible change in which one adult cell type is replaced by another adult cell type-Dysplasia: deranged cell growth of a specific tissue that results in cells that vary in size, shape, and organization |
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Compare the pathogenesis and effects of intracellular accumulations and pathologic calcifications.
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-Intracellular accumulations: buildup of substances that cells cannot immediately use of eliminate
-Pathologic calcifications: abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals |
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Describe the mechanisms whereby physical agents such as blunt trauma, electrical forces, and extremes of temperature produce cell injury.
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-it impairs the cell function-occurs as a result of body impact with another object
-exposure to low intensity heat causes cell injury by inducing vascular injury, accelerating cell metabolism, inactivating temperature-sensitive enzymes, and disrupting cell membrane. -Exposure to cold increases blood viscosity and vasoconstriction and may lead to hypoxic tissue injury -extensive tissue injury and disruption of neural and cardiac impulses |
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Differentiate between the effects of ionizing and nonionizing radiation in terms of their ability to cause cell injury.
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Ionizing radiation: above the UV range, directly break chemical bonds (cancer treatment)
-Nonionizing radiation: below visible light, vibration and rotation of atoms and molecules (thermal energy) |
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State the mechanisms and manifestations of cell injury associated with lead poisoning.
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-absorbed in GI tract or lungs
-childhood lead screening due to long term neurobehavioral and cognitive deficits in children |
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Relate free radical formation and oxidative stress to cell injury and death.
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-Free radicals: highly reactive chemical species with an unpaired electron in the outer orbit of the molecule, unstable and highly reactive, damage cell membranes, inactive enzymes, damage DNA
-Oxidative stress: condition that occurs when the generation of TOS exceeds the ability of the body of neutralize and eliminate ROS |
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Discuss the function of the immune system.
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To monitor, recognize, respond to and cease immune activity. The immune system monitors the body's internal environment for the presence of any pathogen or any changes in cells that may result in tumor formation. Help the body repair/fight off infectious diseases.
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Compare and contrast the innate and adaptive immune response.
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Innate: you are born with it. It includes certain physical, cellular, and chemical barriers throughout the body. It NONSPECIFIC
Active: Acquired immunity that develops in response to antigens. It is SPECIFIC to the antigen. Specificity is determined by B-cells and T-cells. Other way to learn it *innate- consists of physical, chemical and cellular defenses against pathogens. The main purpose of the innate immune response is to immediately prevent the spread and movement of foreign pathogens throughout the body. adaptive- occurs after exposure to an antigen either from a pathogen or a vaccination. This part of the immune system is activated when the innate immune response is insufficient to control an infection. |
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Understand the role of the chemical mediators that orchestrate the immune response.
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Cytokines generated by cells of the immune systems; can be regulatory, pro-, or anti- inflammatory; generate responses by binding to specific receptors on target cells.
interleukins (ILs): produced by macrophages and lymphocytes in the presence of invading microorganisms or inflammatory activation; work to enhance the acquired immune response. interferons (IFNs): produced by macrophages and T lymphocytes; primarily protect against viral infections and help modulate the inflammatory response. tumor necrosis factor alpha (TNF-a): produced by macrophages; important mediator of inflammation; endogenous pyrogen; with prolonged exposure it has the ability to produce coagulation. chemokines: small protein molecules that function to direct WBC migration to the primary site of immune action.colony stimulating factors: subset of cytokines that stimulate hematopoiesis |
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Describe the cellular components of the innate immune response and their functions.
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The innate immune system consists of physical barriers (skin, mucus membranes), cellular components [phagocytes (neutrophils and monocyte/macrophages) and natural killer cells], and complement proteins.
Consists of physical, chemical, cellular, and molecular defenses that are ready for activation and mediate rapid, initial protection against infection |
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Understand the recognition systems for pathogens in innate immunity.
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Pattern recognition by Natural Killer cells: recognize evolutionarily retained patterns (pathogen-associated molecular patterns [PAMPs]) present on the surface of pathogens and in response bind to the pathogen and induce phagocytosis; PAMPs are made up of sugars, lipid molecules, proteins, and modified nucleic acids necessary for.
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Describe the functions of the various cytokines involved in innate immunity.
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Cytokines are low molecular weight proteins that serve as soluble chemical messengers and mediate the interaction between immune and tissue cells.-the cytokines involved in innate immunity include: TNF-a and lymphotoxin; interferons (IFN-y, IFN-a, INF-B), the interleukins IL-1, IL-6, and IL-12; and CHEMOKINES (table 13.2). These substances modulate innate immunity by stimulating the development of cells involved in both innate and adaptive immunity, producing chemotaxis within leukocytes, stimulating acute phase protein production, and inhibiting viral replication.-once an innate immune phagocyte is activated with a pathogen, cytokines are released into the surrounding tissue where they exert their effects.-under normal circumstances the duration of activity of cytokines is relatively short so that a prolonged immune response does not occur.
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Define the role of the complement system in immunity and inflammation.
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The complement system is a powerful effector of both innate and adaptive (humoral) immunity that allows the body to recognize infection and destroy invading organisms. The complement system consists of a group of proteins (c1-c9) that are NORMALLY present in the plasma in an INACTIVE form. Activation of the complement system is a highly regulated process, involving the sequential breakdown of proteins to generate a cascade of cleavage products that are capable of proteolytic enzyme activity. tremendous amplification occurs because the activation of one molecule at one step allows for MULTIPLE activated enzymes at the next step. Comp. activation is inhibited by proteins that are present on normal host cells; thus, its actions are limited to microbes and other antigens that lack these inhibitory proteins.-The reactions of the comp system can be divided into 3 phases:Initial activation- 3 pathways to activate comp system- 1. the alternative pathway, which is activated on microbial cell surfaces in the absence of antibody and is a component of innate immunity. 2. The classical pathway- activated by certain types of antibodies bound to antigen and is part of humoral immunity. 3. the lectin pathway- activated by a plasma lectin that binds to mannose on microbes and activates the classical system pathway in the absence of antibody.The early-step inflammatory process- A central component of complement for ALL 3 pathways is the activation of the C3 protein and its enzymatic cleavage to a LARGER C3b fragment and a SMALLER C3a fragment. The smaller C3a fragment stimulates inflammation by acting as a chemoattractant for neutrophils. The larger C3b fragment becomes attached to the microbe and acts as an opsonin (molecules that coat neg. charged particles on cell membranes and enhance the recognition and binding of phagocytic cells to microorganisms) for phagocytosis.-it also acts as an enzyme to cleave C5 into 2 fragments: C5a fragment that produces vasodilation and increases vascular permeability, and a C5b fragment, which leads to the late-step membrane attack response.The late step membrane attack responses- C3b binds to other complement proteins to form an enzyme that cleaves C5, generating C5a and C5b fragments. C5a then stimulates the influx of neutrophils and the vascular phase of inflammation. The C5b fragments that remain attached to the microbe, initiates the formation of complex comp proteins C6, C7, C8, and C9 into a membrane attack complex protein, or pore, that allows fluids and ions to enter and cause cell lysis.-pathological manifestations associated with comp def. range from increased risk for infections and inflammatory tissue and autoimmune disorders that are the result of impaired activated comp. clearance.
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Characterize the significance and function of major histocompatibility complex (MHC) molecules.
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In order for the adaptive immune response to function properly, it must be able to discriminate between self and no self (foreign and harmful) molecules. The T-lymphocytes are designed to respond to a limitless number of antigens and at the same time ignore self-antigens expressed on tissues. The MHC molecules allow the lymphocytes to do just this. The MHC is a large cluster of genes located on the short arm of chromosome 6. The complex occupies approx. 4 million base pairs and contains 128 different genes, only some of which play a role in immune response. The MHC are divided into 3 classes (I, II, III) based on their underlying function.
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Compare and contrast the development and function of the T and B lymphocytes.
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•B & T lymphocytes originate in red bone marrow from hematopoietic stem cells.
•Maturation Process T cells undergo a two- to three-day maturation process in the thymus. B cells become immunocompetent and self-tolerant in the bone marrow. Naive B cells and T cells are exported to the lymph nodes, spleen, and other secondary lymphoid organs, where encounters with antigens may occur. •General Function B lymphocytes - B cells oversee humoral immunity. T lymphocytes - T cells are non-antibody-producing lymphocytes that constitute the cell-mediated arm of adaptive immunity. |
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Differentiate between the processes of cellular and humoral immunity.
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Humoral immunity is also called antibody-mediated immunity. With assistance from helper T cells, B cells will differentiate into plasma B cells that can produce antibodies against a specific antigen. The humoral immune system deals with antigens from pathogens that are freely circulating, or outside the infected cells.
Cell-mediated immunity is an immune response that does not involve antibodies. Rather, cell mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to antigen. |
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Describe the function of the five classes of immunoglobulins
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1. IgG: function- anti-D complement fixation (blood plasma, crosses placenta)
2. IgE: function- stimulate to release histamine and heparin (protein in plasma membrane of mast cells and basophils) 3. IgD: function- to signal the B cells to be activated. (Protein in plasma membrane of B cells) 4. IgM: function- 10% Ab- Anti A and Anti B/ agglutination and compliment fixation (located:blood plasma) 5. IgA: function-prevents pathogens from gathering to epithelium (blood plasma, milk, tears, saliva, mucus) |
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Describe the function of cytokines involved in the adaptive immune response.
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stimulate the growth and differentiation of lymphocytes. stimulates antigen presentation by class I/II MHCs, activates macrophages and regulates actions of lymphocytes. Cytokines can target specific WBCs
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Explain the transfer of passive immunity from mother to fetus and from mother to infant during breastfeeding.
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Passive immunity is immunity transferred from another source. Maternal IgG antibodies readily cross the placenta during fetal development. After birth the neonate also receives IgG antibodies from the mother in breast milk or colostrum. Therefore, infants are provided with some degree of protection from infection for approximately 3-6 months. Maternal IgG is effective against most microorganisms and viruses that a neonate encounters.IgA is not transferred in utero but IS transferred to the breast fed infant in colostrum. IgA antibodies are associated with mucosal members and provide local immunity for the intestinal system during early life.
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Characterize the development of active immunity in the infant and small child.
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fetal development 5-6 wks., secondary lymphoid organs well developed at birth, IgA and IgM reach adult levels by 1
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Describe the changes in the immune response that occur during the normal aging process.
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The ability of the immune system to protect the body from pathogenic organisms and environmental toxins declines as a result of an overall decline in immune responsiveness. This results from changes in both cell-mediated (T cell) and humoral (B cell) immune responses.
Older adults: More susceptible to infections Have more evidence of autoimmune and immune complex disorders Have a higher incidence of cancer than do younger people Have a weakened response to immunization Comorbid conditions impair normal immune function and compromise the immune responseMultifactorial cause, size of thymus diminishes to 15% or less of its max size affecting T-cell production and function. Production: There may be a decrease in the number of lymphocytes in peripheral lymphoid tissue but the most common finding is a slight decrease in the proportion of T cells to other lymphocytes and a decrease in CD4 and CD8 cells. Function: Lymphocyte’s exhibit altered responses to antigen stimulation with an increased proportion becoming unresponsive to activation. CD4 T lymphocytes are most severely affected because there is a decreased rate of synthesis of the cytokines that stimulate the proliferation of lymphocytes and expression of the specific receptors that interact with the circulating cytokines. Actual B cell function is compromised with age, the range of antigens that can be recognized by the B cells does not change. |
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Name the 5 cardinal signs of inflammation and describe how they occur
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Redness (Rubor) Caused by vasodilation of the arterioles and values that increase capillary blood flow. Accompanied by heat
Swelling (Tumor)Increase in vascular permeability → release of protein-rich fluid (exudate) into the extravascular spaces → Increased capillary osmotic pressure & interstitial osmotic pressure → fluid accumulation in the tissue spaces (edema/swelling) (in short: fluid leaking into the tissues causes swelling) Heat (Calor)Caused by vasodilation of the arterioles and values that increase capillary blood flow. Accompanied by redness . Pain (Dolor)Swelling pushes on the nerve endings Loss of function (Functio laesa) Systemic signs (fever, fatigue)occur when inflammatory mediators enter circulation |
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Name and describe the cells involved in inflammation
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Endothelium:
Line blood vessels Produce anti-platelet and antithrombotic chemicals to maintain potency Release chemicals to dilate/constrict blood vessel depending on need Produce inflammatory mediators Control migration of neutrophils Platelets (thrombocytes): Involved in hemostasis Release inflammatory mediators when activated Leukocytes (WBCs): Neutrophils Arrive early Phagocytic leukocytes Secrete toxic oxygen (H2O2) and NO to destroy pathogens Lymphocytes (B and T cells): Participate in "adaptive" immunity Macrophages: Arrive within 24 hours Phagocytic - clear tissue debris Secrete cytokines, inflammatory mediators (leukotrienes, prostaglandins) Eosinophils: Secrete mediators in response to allergies or parasites Basophils and Mast cells Secrete histamine and other inflammatory mediators (TNF) |
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Differentiate between histamine, arachidonic acid metabolites, cytokines, nitric oxide, and oxygen free-radicals including their source and function
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Histamine:
One of first mediators released Dilation of arterioles Increased vascular permeability Temporary while leukotrienes are being manufactured Arachidonic acid metabolites: -Arachidonic acid is an omega-6 fatty acid found in cell membranes -Cytokines formed depend on the enzyme that acts on arachidonic acid Tumor Necrosis Factor (TNF) and Interleukins (IL): -Cytokines produced by macrophages, lymphocytes, endothelium, and other cells -Many roles: Induce endothelial cells to express adhesion molecules Release other cytokines Release toxic oxygen Induce acute-phase responses of systemic inflammation:Fever, ↑ HR, anorexia, ↑ neutrophils, ↑ corticosteroids Nitric oxide:Smooth muscle relaxation (vasodilation) Oxygen free-radicals Increase expression of cytokines Very reactive - can cause cellular damage |
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Differentiate between the vascular and cellular changes seen in inflammation, including the cause of each
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Vascular changes:
Transient vasoconstriction followed by vasodilation Induced by histamine and nitric oxide Increased vascular permeability follows Chemical mediators (histamine, bradykinin, etc..) bind to endothelial cells, cause contraction of cells, create gaps between endothelial cells Movement of protein rich fluid (exudate) into extravascular spaceLoss of fluid from blood vessels → more concentrated bloodSlow blood flow due to ↑ viscosity → clotting Aids in reducing spread of pathogen to other parts of the body Cellular changes: Changes in endothelium and movement of leukocytes into area of injury Recruitment involves chemical mediators (mast cells) |
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Describe the process of the cellular phase of inflammation (margination, adhesion, etc.)
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Margination:
Accumulation of leukocytes at site of injury Adhesion:Cytokines stimulate endothelial cells to express adhesion molecules (selectins) Bind to leukocytes (tethering) Slowly roll along endothelial lining (rolling) Come to rest and adhere to intercellular adhesion molecules (ICAMs) - this is "firm adhesion" Transmigration: Adhesion causes endothelial cells to separateLeukocytes move between endothelial cells into tissue spaces Chemotaxis: Movement of leukocytes to site of injury directed by chemokines - chemical gradient Leukocyte activation: Chemicals at site of injury Phagocytosis: Recognition and adherence: Depends on type of cell - either by receptors on cell or by opsonization Engulfment: Binding triggers endocytosis Pseudopods surround and enclose the particle in a phagosome Intracellular killing: Phagosome merges with lysosome to destroy pathogen Lysosome contains microbe-killing enzymes |
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Differentiate between the types of exudates and provide an example of each
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Serous: Skin blisters, pericarditis
Fibrinous: Adhesions following surgery Catarrhal: Runny nose as with common cold Purulent: Abscesses, boils Hemorrhagic: Fulminating Infection |
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Describe the process of chronic inflammation
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Long-term and self-perpetuating response to recurrent inflammation or irritants that do not spread rapidly
Chronic inflammation is characterized by infiltration by macrophages and lymphocytes and presence of fibroblasts in tissue -Non-specific: Diffuse accumulation of macrophages and lymphocytes in the tissue Fibroblasts become activated and create scar tissue that replaces normal tissue -Granulomatous: A 1-2 mm lesion consisting of macrophages surrounded by lymphocytes Associated with foreign bodies (asbestos, splinters, etc.) and some microorganisms (TB, syphilis, etc.)All are poorly digested by phagocytic cells - difficult to eliminate |
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Define lymphadenitis and describe the cause
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Inflammatory mediators produced by inflammation cause localized inflammation when drained into lymph nodes
In general: When associated with inflammation: palpable, painful nodes When associated with neoplasm: painless nodes |
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Describe how fibrous tissue replaces damaged tissue
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Fibrous Tissue Repair:
Replacement of damaged tissue with connective tissueUsually occurs with severe or repeated injury to both parenchymal (functional) and stromal (supportive) tissue Generation of granulation tissue: Moist, red connective tissue Angiogenesis creates new blood vessels from existing ones Foundation of new tissue Fibrogenesis: Influx of fibroblasts which lay down loose extracellular matrix (ECM) made of fibronectin, hyaluronic acid and proteoglycans Proteoglycans (hydrophilic) are responsible for swelling Scar formation: Fibroblasts increase synthesis of collagen Vessels in granulation tissue degenerate Mature scar develops (fibroblasts, collagen, ECM) |
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Differentiate between healing by primary intention and secondary intention
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Primary Healing: Suture wound, faster
Primary Intention wound margins are neatly approximated. Ex. surgical incision More granulation tissue 3 Phases Initial (inflammatory) Granulation Maturation Scar Secondary Healing: Pressure ulcer or burn, slower Wide irregular margins with extensive (some degree of) tissue loss Ex. Trauma May have wound edges that cannot be approximated Inflammatory reaction may be greater than primary healing Results in more debris, cells and exudate/ ulcerating Essentially same as healing by primary intention. ---major differences are greater defect and gaping wound edges Healing and granulation take place from the edges inward and from the bottom of the wound upward. Results in more scaring |
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Describe the 3 phases of wound healing
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Inflammation: white blood cells fight off rogue bacteria which causes swelling
Proliferation: fibroblasts and collagen stitch skin back together to close the wound (there is now a scab) Maturation: remodeling the skin |
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Define “prion” and give an example of a disease associated with these
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Protein particles - mutation of normal host protein that cause non-inflammatory degeneration of neurons
ExamplesCreutzfeldt-Jakob disease and Mad Cow disease |
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Define “virus” and give an example
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Virus:
Organisms composed of protein coat and nucleic acid core Cannot replicate outside living cell Need to use organelles of host cells to reproduce May insert into genome of host cell and stay dormant for many years Examples: herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, HIV |
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Describe 5 complications of HIV
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The virus that can cause the acquired immunodeficiency syndrome (AIDS)
Profound suppression of immune system Opportunistic infections: bacterial pneumonias (Most common in the US) Pneumocystis jiroveci (carinii) Oral thrush Esophageal candidiasis Mycobacterium tuberculosis Pneumocystosis(PCP) CMV HSV/HZV Malignancy Body wasting CNS degeneration |
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Describe how HIV infects cells
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a retrovirus that attacks CD4+ T helper lymphocytes. As a result, immune system is compromised
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Describe transmission of HIV including who is at risk
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Transmission:
Blood/Mucous Membranes Blood to blood contact or perinatally infected blood, semen, or vaginal secretions come into contact with mucous membranes or bloodstream of another Sores/Broken Skin Vaginal mucousa, anal mucousa, wounds and sores on skin Infected person can pass the virus in the absence of symptoms Window period Whose is at risk: Risk behaviors- Condomless sex Multiple sexual partners Drug use Sharing needles, syringes or other drug injection Babies born to mothers with HIV ****CANNOT be spread by casual contact (handshake) NOT spread by insects**** |
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Describe bacteria and give 3 examples of bacteria that cause disease
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Without a nucleus, unicellular, they don’t need a host & are highly adaptable.
Ex. Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli Spirochetes – Borrelia burgdorferi Treponema pallidum (syphilis) Mycoplasmas – Mycoplasma pneumonia |
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Define “rickettsiaceae” and “chlamydiaceae” and provide an example of each, including the disease they cause
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Organisms that combine characteristics of viruses and bacteria
Cannot replicate outside a host cell Produce rigid cell wall, reproduce asexually, and contain both DNA and RNA Depend on host cell for nutrients Examples Rickettsiaceae transmitted by arthropod bite (Rocky Mountain Spotted fever) Chlamydiaceae transmitted directly (Chlamydia trachomatis) |
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Name 2 fungal infections
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Organized nucleus, sexual or asexual reproduction
Yeasts - single celled Molds - hyphae Examples: Histoplasma capsulatum, Candida albicans, Tinea pedis |
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Name 2 parasitic infections
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Organisms that derive benefit from a host
Unicellular or multicellular Protozoa: Giardia lamblia, Trypanosoma bruceiHelminths: Ascaris Arthropods: Ticks, fleas, lice, scabies |
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Describe the 5 stages of infection
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Incubation pathogen is replicating slowly, no symptoms in host
Prodromal initial appearance of symptoms, mostly constitutional Acute maximum replication of pathogen, maximum symptoms, inflammatory process and tissue damage occurring Convalescent containment of pathogen, tissue repair, resolution of symptoms Resolution total elimination of pathogen without residual signs and symptoms of disease |
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Describe 4 host defenses that protect the body from infection
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Prevent access of microbes to the body
Secretions in mucous membranes destroy bacteria Lysozyme in tears dissolve peptidoglycan in bacterial wall Skin:Normally coated with many bacteria (Staphylococcus epidermidis, Candida albicans) Low pH and presence of fatty acids on skin surface inhibit microbial growth Moist skin more susceptible to infection Heat and humidity aggravate microbial growthSuperficial lesions/insect bites allow microbial entry Genitourinary tract: Urinary tract is normally sterileUrination flushes bacteria from system and disrupts adhesion Short urethra, reflux, obstruction promote bacterial growth Respiratory tract: Many bacteria, viruses, etc.. inhaled daily Mucociliary blanket lining nose and upper respiratory tract trap microbes Smoking damages this Goblet cells secrete mucous and trap microbesCilia in upper airway move encapsulated bacteria to back of throat where they are swallowed or expelled Alveolar macrophages destroy small organisms that travel down airway Gastrointestinal tract: Most pathogens are transported via food contaminated with fecal material Gastric acid destroys pathogens in stomachViscous mucous layer coats gut and entraps microbes Pancreatic enzymes and bile detergents destroy organisms IgA secreted by mucous membranes in gut Normal bacterial flora compete with pathogens for nutrients |
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Describe 3 ways in which pathogens have increased virulence
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Toxins: usually bacteria, influence normal function of host cells
Exotoxins - proteins released by bacteria during growth Enzymatically alter components of host cell leading to dysfunction or death of the host cell Endotoxins - lipid and polysaccharide in cell wall of gram-negative bacteria Adhesion factors: special filaments that enable pathogens to attach to their host Evasive factors: means by which pathogens avoid immune system of host Capsules, chemical release, ability to survive within leukocytes or caustic environments Invasive factors: means by which pathogens invade their host Enzymes that destroy cell membranes or connective tissues |
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Differentiate active and passive immunity
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Describe immunotherapy
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Supplementing or stimulating immune system of host to limit spread of pathogen
Intravenous immune globulin (IVIG) Cytokines Immunization |
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Name the 3 types of cancer most prevalent in males and females and differentiate those from the 3 types of cancer most likely to cause death in males and female
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3 types of Cancer in males and females
· Lungs · Colon · Prostate ****MEN • Mortality rate from lung cancer is higher in men than women. • More men than women die from cancer-related deaths each year. • Esophageal cancer is more prevalent in men than in women. • Cancer with the highest incidence among men is prostate cancer. • Men are more likely to develop liver cancer than women. • Head and neck cancer occurs more frequently in men than women • Bladder cancer is at least three times as common in men as in women. ****WOMEN • Cancer with the highest death rate among women is lung cancer. • Nonsmoking women are at a greater risk than men of developing lung cancer. • Thyroid cancer is more prevalent in women than men. • Cancer with the highest incidence among women is breast cancer. • Women are less likely to have colon cancer screenings than men. |
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Define differentiation
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Differentiation is the process by which cells change in structure and become capable of carrying specialized functions.
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Identify a type of cancer based on it’s suffix
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Tumors are often named by adding
–oma to the type of parenchymal tissue from which the growth originated • Adenoma – neoplasm of glandular tissue • Osteoma – neoplasm of bone • Malignant neoplasm of epithelial tissue origin end in suffix –carcinoma • Adenocarcinoma – malignant neoplasm of glandular tissue • Malignant neoplasm of mesenchymal origin end in suffix –sarcoma– Osteosarcoma – malignant neoplasm of bone Extra notes* Benign: -Lipoma (fat cells) -Glioma (connective tissue cells of the central nervous system) -Leiomyoma (smooth muscle of the uterus) -Chondroma (in or on cartilage cells) Malignant:-carcinomas: Malignant epithelial tumors -Adenocarcinoma (Coming from or creating ducts or glands) -sarcomas: Malignant connective tissue and bone tumors -Rhabdomyosarcomas (skeletal muscle) Cancers of lymphatic tissue are lymphomas Cancers of blood -forming cells are leukemias Carcinoma in situ (CIS) Preinvasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma |
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Differentiate benign neoplasms from malignant neoplasms
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Benign: Grow slowly, has capsule, non-invasive, well differentiated, low mitotic index, do not metastasize
Malignant: Grow rapidly, not encapsulated, invasive, poorly differentiated, high mitotic index, can spread distantly (metastasis) |
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Describe the characteristics of cancer cells
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Abnormal, rapid proliferation
Loss of cell differentiation (anaplasia) Genetic instability Growth factor independence Cell density- dependent inhibition Cell cohesiveness and adhesion Anchorage dependence Cell to cell communication Life span Antigen expression Production enzymes, hormones, etc.Cytoskeletal changes Extra notes* Cancer is a cellular disease. Cancer Cells Lack Differentiation Cancer cells are unspecialized and do not contribute to the functioning of a body part. Cancer Cells Have Abnormal Nuclei The nuclei of cancer cells are enlarged and may contain an abnormal number of chromosomes.Cancer Cells Have Unlimited Potential to Replicate Cancer cells are immortal and keep on dividing for an unlimited number of times. Cancer Cells Form Tumors Cancer cells pile on top of one another and grow in multiple layers, forming a tumor. Cancer Cells Have No Need for Growth Factors (chemical signals) Cancer cells keep on dividing, even when stimulatory growth factors are absent, and they do not respond to inhibitory growth factors. Cancer Cells Gradually Become Abnormal The process of carcinogens is a multistage process that can be divided into three phases: initiation, promotion, and progression. Cancer Cells Undergo Angiogenesis and Metastasis Tumors require a well-developed capillary network to bring nutrients and oxygen. Angiogenesis is the formation of new blood vessels. When cancer cells begin new tumors far from the primary tumor, metastasis has occurred. |
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Describe how cancer spreads through the body
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The spread of cancer cells from the place where they first formed to another part of the body. In metastasis, cancer cells break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor in other organs or tissues of the body. The new, metastatic tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the lung, the cancer cells in the lung are breast cancer cells, not lung cancer cells.
(direct invasion spreading of cancer cells throughout the body metastatic spread through sentinel node) Angiogenesis formation of new blood vessels for growing and to metastasize |
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Differentiate proto-oncogenes from tumor suppressor genes
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Tumor Suppressor Genes:
Genes that turn OFF or DECREASE the rate of celldivision. Genes that repair DNA mistakes. Genes that play a role in apoptosis (Programmed cell death that follows a sequence of controlled steps that led to self-destruction). If these genes mutate or are inactivated, cells pass through the checkpoints and divide in an uncontrolled manner which may lead to abnormal cell growth and defective apoptosis - all which can cause cancer Proto-oncogenes: Genes that turn ON or INCREASE the rate of cell division. When these genes are active CELLS GROW and DIVIDE. When normal cells stopdividing, the genes turn off. |
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Describe how cancer cells survive destruction.
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six different contributing factors that promote cancer survival
DNA repairs defects- This is a normal mechanism our body uses. If there is damage to DNA these genes will come in and repair them to make the cell normal again. When there is a deficit in these repair genes mutations can occur that cause cancer. Also this mechanism promotes cancer cell survival because it can repair damage in proto-oncogenes, genes that impact apoptosis and tumor suppressor genes. Also when Defects in growth factor signalling pathway- normal cells need signal from growth factor to the nucleus to proliferate. Cancer cells stimulate their own growth using mutations in genes that control growth factor signaling pathways (MAP Kinase signaling, JAK/STAT signaling, & PI3K/AKT1). When these pathways are disrupted/altered the cell cycle will be altered. Evasion of apoptosis- many ways cancer cells can do this *said in class not to focus on the mechanisms because we didn't spend time talking about them *Evasion of cellular senescence- cancer cells have a high level of telomerase and prevention of telomerase shortening that prevent the cell from aging and senescence (loss of cell power of division and growth). Development of sustained angiogenesis- able to make its own blood supply. Allows for tumors to grow and spread (metastasis). Invasion and metastasis- multiple genes and molecular/cellular pathways are involved in invasion and metastasis. Specifically, MET proto-oncogenes that are present in stem cells and cancer cells are the main genes that regulate invasive growth |
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Describe the causes of cancer
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damage to genes the encode growth factors
+mutation: caused damages to the genes +result of chemical, environmental or viral exposure |
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Define paraneoplastic syndrome and provide 3 examples
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set of signs and symptoms that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells.
Can be the first symptom to occur prior to the diagnosis of tumor Frequently occurs as a result of a substance produced by tumor (PTHrP, ACTH-like substance, ADH, ectopic cortisol, etc) Most commonly associated with lung, breast, ovary, lymphatic system malignancies Incidence 2-20% malignancies____Most commonly with lung or breast-less with ovary and lymph |
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Name 3 adverse outcomes from antibiotic resistance
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Extended hospitalization
Significant morbidity Increased mortality |
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Describe the 2 genetic methods by which bacteria develop resistance to antibiotics
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Spontaneous mutation:
a.Random alteration in DNA b.Resistance develops slowly c.Usually resistance to only ONE drug Conjugation : a.Transfer of genetic material from one organism to the other b.“Resistant gene” implanted in bacterial DNA c. Requires “implantation” gene from host, as well d. Together constitute an R factor (resistance factor) |
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Describe the process by which antimicrobial resistance permits growth of resistant bacteria
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Antibiotics kill off the normal flora. Without normal flora that is no competition. This allows for the promotion of growth.
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Name 4 mechanisms by which bacteria resist destruction by antibiotics
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Describe the process of erythropoiesis
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-pluripotent stem cell becomes an erythrocyte colony
-forming unit (ecfu) -the hormone erythropoietin (EPO) stimulates the ecfu to develop into an erythroblast -erythroblast (aka erythrocyte precursors) develop a nucleus, ribosomes, golgi, as well as hemoglobin -when hemoglobin production is complete, the nucleus shrives and is discharged from the cell-protein making machinery begins to disintegrate-cell is now considered a reticulocyte -reticulocytes leave the bone marrow and enter the circulating blood -when the last of the ribosomes disintegrate and disappear, the cell is considered to be a mature erythrocyte |
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Differentiate leukocytes by origin (lymphoid vs. myeloid)
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From progenitor cells in bone marrow
1.Lymphoid progenitors – differentiate into lymphocytes and are released into blood stream •Fully mature in lymphoid organs 2.Myeloid progenitors – differentiate into all other white blood cells. a.Monocytes released into blood stream and mature b.Granulocytes mature in bone marrow–Some immature granulocytes reserved in bone marrow and are activated and released when needed |
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Describe the process of platelet development
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•Platelets
–Formed from megakaryocytes –Stimulated by thrombopoietin *developmental path of thrombocytes (platelets) The production of platelets is called thrombopoiesis From the myeloid stem cell, a committed cell called amegakaryoblast (meg-ă-kar′ē-ō-blast; mega = big) is produced It matures under the influence of thrombopoietin to form a megakaryocycte Each megakaryocycte then produces thousands of platelets. |
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Describe the stages of normal hemostasis including the function of vonWillebrand factor, fibrinogen, and fibrin
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1. Vessel Spasm-
a.) Vascular Spasm occurs during small breaks in smooth muscle. b.) Significantly reduce blood flow until other mechanisms occur. 2. Platelet plug formation: platelets stuck to wound and each other to form a plug What occurs during Platelet Plug Formation?a.) Platelets stick to exposed collagen fibers or broken vessels. What is the purpose of von Willebrand Factor? b.)von Willebrand Factor helps to stabilize platelet-collagen adhesion. 3. Coagulation: fibrin strands form a tough clot to seal the branch a.) Coagulation reinforces platelet plug with fibrin threads b.) Used for larger breaks 4) Fibrinolysis: fibrin clot is digested *FibrinogenConverted into fibrin by the coagulation cascade *Fibrin- The glue that binds platelets, endothelial cells, and other formed elements together.- sticky, threadlike protein- converts the soft, liquid platelet plug into a more solid mass by the process of coagulation- normally found in plasma and in platelets in its inactive form, fibrinogention cascade *Coagulation Cascade A series of reactions that occur at the surface of platelets and/or damaged endothelial cells- relies on clotting factors Goals are: 1. Produce Xa 2. Produce thrombin 3. Produce fibrin |
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Differentiate the intrinsic and extrinsic pathways of the coagulation cascade
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intrinsic pathway-coming from inside the blood vessel...activates when platelets run into the collagen fiber can also happen by itself when we are sitting for too long
a) Factor XII (contact factor) circulating in the blood is activated by contact with exposed subendothelial basement membrane at the time of tissue or blood vessel injury. b) Prekallikrein, High Molecular Weight Kininogen (HMWK) and Factor XII interact together to activate Factor XI (also a contact factor). c) Factor XIa activates factor IX in the presence of CALCIUM ionsd) Factor IX combines with Factor VIII and CALCIUM ions on the phospholipids layer (PPL) of the platelet surface to active Factor X. extrinsic pathway-injured blood vessels and injured tissue around it a) Tissue thromboplastin (Factor III) is released from cells at the site of injury. b) Tissue factors, and calcium ions, binds with Factor VIIc) Factor VII is activated to its VIIa form and in the presence of CALCIUM IONS activates factor X |
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Describe the role of calcium in the coagulation cascade
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Calcium ions assist in the coagulation process when forming the enzyme complex that eventually activates other clotting factors. Calcium also is involved in activating other platelets.
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Describe how fibrin is produced in the final steps of the common pathway
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the tissue factor (extrinsic) pathway and the contact factor (intrinsic) pathway. These pathways meet in a final common pathway whereby factor Xa converts prothrombin to thrombin, which then cleaves fibrinogen to fibrin.
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Describe the role of antithrombin III, Protein C, and Protein S in coagulation
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Antithrombin III- Selective serine protease inhibitor: Produced in the liver. Forms a complex that inactivates thrombin (IIa).
(Inactivates coagulation factors and thrombin) Protein C-Produced in the liver. Naturally-occurring inhibitor of coagulation system. Inactivates factors V and VIII (*Protein C = activated by Protein S cofactor activated protein C (APC) = degrades activated Factors V and VIIIAPC= degrades factors = terminates coagulation pathway) Protein S-Produced in the liver. Naturally-occurring inhibitor of coagulation system. Acts with protein C. (Accelerates Protein C) |
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Describe how a clot is dissolved under normal circumstances.
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dissolves minor clots that develop on atherosclerotic plaques or minor roughened areas of vessels and clots in tissue that has been healed
induced by plasmin Fibrinolysis–Plasminogen → plasmin– Digests fibrin strands–Digests several clotting factors |
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Explain how thrombocytosis, factor V Leiden, and deficiencies in protein C or antithrombin III contribute to hyper-coagulability
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What is thrombophilia? group of conditions of excessive clotting (Hypercoagulability) Primary •Abnormally high levels of free thrombopoietin due to abnormal thrombopoietin receptors on platelets– Secondary •Increased production of thrombopoietin due to tissue damage •Surgery, infection, cancer, inflammatory disease –Factor V Leiden mutation – Factor V cannot be inactivated by protein C •Venous thrombosis •–Prothrombin gene mutation – elevated prothrombin levels •Venous thrombosis 3x greater than norma l•–Hereditary deficiencies of protein C, protein S, or antithrombin III |
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Name the 4 types of Inherited Thrombophilia
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1. Factor V "Leiden" mutation
2. Protein C Deficiency 3. Protein S Deficiency 4. Antithrombin deficiency |
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Factor V "Leiden" Mutation
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genetic mutation of Factor V = unresponsive to Protein C inhibition
uninhibited Factor V = constant coagulation = Hypercoagulability |
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Factor V Thrombophilia: Mechanism
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mutated Factor V = not inhibited by Protein Cactive
Factor V = over produces Thrombin = Excess Fibrin production Excess Fibrin = Excessive clotting in Veins |
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What 2 possible conditions result from Factor V mutation?
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DVT = deep vein thrombosis (clotting usually in veins)
Pumonary Embolism |
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Name 2 ways a person may develop hypercoagulability
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Acquired disorders– Stasis of blood flow due to immobility–– MI•Venous congestion–– Hyper-estrogenic states/hormone-based contraceptives Increase synthesis of clotting factors Suppress or Reduce synthesis of antithrombin III *Oral Contraception Smoking Nephrotic Syndrome Hyperestrogenemia |
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Name the 2 types of Thrombophilia Inherited Thrombophilia
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genetic mutations of anticoagulant mechanisms (family history of clotting)
Acquired Thrombophilia = clotting disorder not present at birth, but develops due to illness/disease |
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Describe the mechanism behind heparin induced thrombocytopenia
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What is heparin induced thrombocytopenia?
severe decrease in platelet count (<150,000) in response to heparin 1.Thrombocytopenia–Reduced number of platelets •Decreased production or decreased survival •2.Heparin-induced thrombocytopenia (HIT) •Immune reaction against heparin-platelet factor 4 complex (normal component – binds to heparin) •Immune complexes activate platelets and lead to thrombosis–Platelets release particles that activate thrombin–Thrombin does what? acts on the clotting factor fibrinogen to form fibrin •Thrombocytopenia due to overuse of platelets |
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Differentiate immune thrombocytopenic purpura from thrombotic thromocytopenic purpura
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Immune thrombocytopenic purpura (ITP)
•Autoimmune disorder •Antibodies against receptors •Create circulating immune complexes •Abnormal bleeding •More susceptible to phagocytosis and removal by spleen •Steroid is one of the treatment Thrombotic thrombocytopenic purpura (TTP) •Deficiency of enzyme that degrades vWF(ADAMTS13) •Platelets adhere and aggregate |
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*not to sure about the answer here Describe how the COX pathway is involved in platelet aggregation |
•Both of these medications block the cyclooxygenase pathway (COX)
•↓ prostaglandins •↓ thromboxane •↓ platelet aggregation Under influence of COX-1, prostaglandins maintain and protect the gastric mucosa, maintain normal platelet function through the formation of thromboxane and prostacyclin, and regulate renal blood flow. |
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Describe 3 coagulation factor deficiencies
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Coagulation factor deficiencies
–Hemophilia A •1 in 5000 male live births •Genetic factor VIII deficiency •–Hemophilia B – Christmas disease•Genetic factor IX deficiency •–Von Willebrand Disease •1 in 1000 persons •Genetic deficiency or defect in vWF •Platelets cannot adhere to subendocardial membrane |
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Describe how liver failure contributes to coagulopathies
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it creates a bleeding disorder. Liver failure –Many clotting factors are synthesized by liver –Liver disease results in reduction of these clotting factors hepatocyte loss - diminishes synthetic function (decrease synthesis of clotting factors) thrombocytopenia |
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Describe the process of disseminated intravascular coagulation
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–Widespread coagulation AND bleeding
–Caused by endothelial damage (viruses, infections, autoimmune disorders, etc.) a)Widespread activation of coagulation response b)Massive clot formation consumes all coagulation proteins and platelets c)Hemorrhage followsd) Treatment : treat what is causing this and replace |
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Describe the presentation of a patient with sickle cell disease
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a)Sickle cell
•Inherited abnormality in hemoglobin S synthesis •10% of black Americans carry the trait •Deoxygenation and dehydration cause cells to sickle •Hemolysis (ruptured cells removed by spleen) and vascular occlusion can occur The most common clinical manifestation of SCD is vaso-occlusive crisis. A vaso-occlusive crisis occurs when the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied and resultant pain |
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Describe thalassemia and differentiate alpha from beta thalassemia
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•Genetic disorders of hemoglobin synthesis
•Either α or β chain is deficient •Result in small, pale cells •Accumulation of unaffected chain results in early hemolysisi. α-Thalessemia – more common in Asiansii. β-Thalessemia (Cooley anemia) – more common in Mediterranean populations (southern Italy and Greece) iii.BOTH are common in Africans and African Americans |
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Describe iron deficiency anemia and name the leading cause
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•Dietary deficiency, bleeding, increased iron demand
•Chronic blood loss is most common in Anemia •Most iron is recycled •Lack of iron impedes production of hemoglobin |
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Describe vitamin B12 deficiency and name who is most at risk
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•Essential for DNA synthesis and nuclear maturation
•Deficiency usually due to dietary deficiency–B12 is present in foods of animal origin–Strict vegetarians need to supplement •Binds to intrinsic factor in stomach, travels to intestine, is absorbed and used •Deficiency causes large cells due to excessive cytoplasmic growthShort life span |
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Describe folic acid deficiency and name who is at greatest risk
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•Required for DNA synthesis and RBC maturation
•Deficiency usually due to dietary deficiency–Found in green, leafy vegetables–Much lost by reheating •Some drugs interfere with absorption–Usually drugs to treat seizure disorder •Produces large cells |
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Describe neutropenia and describe the risks associated with the condition
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•Neutropenia
–Neutrophils are primary WBC and involved in immune defense –Lack of neutrophils can lead to infection 1.Congenital – inherited – rare 2.Acquired a)Autoimmune – SLE and RA b)Infection-related c)Drug-related |
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Differentiate Hodgkin lymphoma from non-Hodgkin lymphoma
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•Non-Hodgkin Lymphoma
–B (more common) or T cell neoplasms –Cause is not known –Commonly originate in lymph nodes and can spread –Many classifications –Manifestations depend on type and stage •Swollen, painless nodes •Constitutional symptoms(fever etc.) •Risk of infection (when we have infection of WBCS)–Chemo leads to remission in 60-80% of cases •Hodgkin lymphoma –Specialized form of lymphoma –Cause unknown –Disease more common in people younger than 40 and adults over 55 –Reed-Sternberg cellis a cell that has a •Mirrored nucleus |
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Differentiate acute from chronic leukemia
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•Acute- sudden onset–Progenitor cells(that can only create a few other cells) –Usually sudden onset–
•Chronic- slow–Fully differentiated cells–Slow progression |
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Differentiate myeloblastic from lymphoblastic leukemia
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•Myeloblastic- (Myelo line)–Originating in myeloid line–
•Lymphoblastic (lympholine)–Originating in lymphoid line |
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Differentiate ALL, AML, CLL, and CML with regard to population at risk, cell type involved, symptoms, and prognosis
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Population @ risk ALL: Most common in Children with a 85% survival while Adult can have only 65% survival Cell type –Neoplasms of precursor B or T lymphocytes •Most are pre-B cell type (75%) Symptoms and prognosis: –Causes anemia, neutropenia, and thrombocytopenia –Increase in blood viscosity AML: Most common in Adult cell type:–Increased numbers of undifferentiated blast cells which crowd the marrow and suppress other progenitor cells Symptoms and prognosis: –Causes anemia, neutropenia, and thrombocytopenia –Increase in blood viscosity CLL: –More common in older adults –Rare in people < 45 years of age –Malignancy of B lymphocytes –Poor production of plasma cells – ↓ gamma globulinemia (decrease in antibodies) CML: –Primarily a disorder of older adults –CML cells contain the Philadelphia chromosome-(genetic marker)forms when two chromosome breaks –Splenomegaly(enlarged spleen) - painful –Immature WBCs released in blood stream –Anemia, fatigability, infections |
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Define multiple myeloma and describe the presentation
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This is a bone marrow (B cell) cancer characterized by the proliferation of malignant plasma cells that can aggregate into tumor masses and then become distributed throughout the skeletal and organ systems resulting in multiple organ damage.
presentation: Bone marrow Lytic Lesions in the bone that punch holes in the bone M protein and Bence jones protein |
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Acute Luekemias |
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Chronic Luekemias |
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Is Bone pain a symptom of multiple myeloma? T/F |
True |
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Intrathecal combination chemotherapy is used to prevent relapse of acute lymphoblastic leukemia ALL in the central nervous system CNS , which is a sanctuary for ALL cells. This treatment is known to cause significant and persistent ___________ in many children. |
Cognitive impairment |
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What is proteolysis? |
The breakdown of protein |
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Apoptosis is |
Programmed cell death |
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What is ischema? |
Drop in blood flow |
