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102 Cards in this Set
- Front
- Back
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What is required for apoptosis that is not required for necrosis?
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ATP
apoptosis: programmed cell death |
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When does the intrinsic pathway of apoptosis happen?
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Intrinsic pathway (aka mitochondrial pathway)
During embryogenesis, hormone induction (menstruation), and atrophy (endometrial lining during menopause) as a result of injurious stimuli (radiation, toxins, hypoxia) |
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How does the intrinsic pathway happen?
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There are changes in the levels of anti-apoptotic proteins (they decrease, along with bcl-2), and pro-apoptotic proteins increase (bax, bak) - which lead to increased mitochondrial permeability and release of cytochrome c (which interacts with apaf-1 causing self cleavage and activation of capsase 9)
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What do both of the apoptotic pathways lead to?
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activation of cytosolic caspases that mediate cellular breakdown
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How does the extrinsic pathway happen?
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occurs with ligand receptor interactions (FAS ligand binding to Fas (CD95) - which activates caspases) or immune cell (T killer) release of perforin and granzyme B
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What is apoptosis characterized by?
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cell shrinkage, nuclear shrinkage, basophilia (pyknosis), membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karylolysis), and formation of apoptotic bodies that
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Does apoptosis cause significant inflammation?
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No! Necrosis does
apoptosis is PROGRAMMED cell death - an organized death process |
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What is necrosis?
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enzymatic degradation of a cell resulting from exogenous injury - occurs in a living cell
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What is necrosis characterized by?
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enzymatic digestion and protein denaturation with the release of intracellular components
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Where does coagulative necrosis occur?
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heart, liver, kidneys - results usually from sudden cutoff of the blood supply
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Where does liquefactive necrosis occur?
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In the CNS and in abscesses - from enzymatic liquefaction of necrotic tissue
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What are irreversible cell changes?
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Nuclear, pyknosis (nuclear shrinkage, basophilia), karyorrhexis (nuclear fragmentation, and karyolysis (fading of nuclear material), Ca2+ influx, plasma membrane damage, lysosomal rupture, mitochondrial permeability
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What is caseous necrosis - where does it occur?
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A combination of coagulative necrosis and liquefactive - cheese like from T-cells, macrophages, IFN, and cytokines - seen in granulomas (ex. TB)
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What is fat necrosis - where does it occur?
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liberation of enzymes - auto digestion - occurs in the pancreas - soap formation occurs can also occur in trauma to tissue with high fat content (breast)
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What is fibrinoid necrosis - where does it occur?
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deposition of fibrin proteinaceous material in walls of blood vessels - immune mediated vascular damage
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What is gangrenous necrosis? What are the 2 types?
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from interruption of the blood supply often occurs in the bowels or extremities.
dry: ischemic coagulative necrosis wet: ischemic liquefactive necrosis - infected with bacteria |
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What are reversible cellular changes?
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cellular swelling, nuclear chromatin clumping, decreased ATP synthesis, decreased glycogen, fatty change and ribosomal detachment
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What are free radicals?
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molecules that have a single unpaired electron in their outer orbit - induces cell injury through membrane lipid peroxidation, protein malformation, and DNA breakage
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What produces free radicals?
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radiation, metabolism of drugs, redox reactions, nitric oxide, transition metals, leukocyte oxidative burst, reperfusion after ischemic injury
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How are free radicals degraded?
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intracellular enzymes i.e. superoxide dismutase (mutated in people with ALS), catalase, or glutathione peroxidase, spontaneous decay, antioxidants (vitamins A, C, E)
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What is a person at risk for after thrombolytic therapy?
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free radical injury - because reperfusion after anoxia induces free radical production (superoxide) and is a major cause of cell injury
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what does bcl-2 do?
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inhibits apoptosis
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what does bax do?
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facilitates apoptosis
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What does p53 do?
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decreases transcription of bcl-2 and increases transcription of bax - inhibiting apoptosis
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What are the two types of infarcts? Where do each tend to occur?
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Red (hemorrhagic) - occurs in areas that have redundant blood supply or following reperfusion injury: lung (brochial and pulmonary artery), liver (portal vein and hepatic artery), intestine (multiple anastamoses)
Pale: occur in solid tissues with only one blood supply (kidneys, heart, spleen |
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What type of infarct do you get following reperfusion injury?
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Red (hemorrhagic)
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What organs get red (hemorrhagic) infarcts?
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intestine, lungs, liver
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What organs get pale infarcts?
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kidney, spleen, heart
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What are the signs of inflammation?
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tumor (swelling), rubor (redness), calor (heat), dolor (pain), functio laesa (loss of function)
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What is inflammation?
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vascular response to injury
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What is the process of inflammation?
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exudation of fluid from vessels, attraction of leukocytes to area of injury (engulf and destroy bacteria), activation of chemical mediators, proteolytic degradation of cellular debris, restoration of injured tissue
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What is the first step in inflammation?
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Fluid exudation - increased vascular permeability, vasodilation, endothelial injury
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What molecules recruit neutrophils to sites of injury/inflammation?
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CILK
C5a, IL-8, Leukotriene B4, Kallikrein |
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What is the time period for acute inflammation?
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rapid onset (seconds to minutes) and lasts minutes to days
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What is the time period for chronic inflammation?
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lasts months to years
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What are the steps in inflammation?
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1. injury occurs to an area
2. chemical mediators are released from damaged tissues - causes vasodilation of nearby tissues so cells and fluid can get to damaged tissue (however initially a period of vasoconstriction to decrease blood supply to the damaged tissue) 3. leukocyte activation - emigration, chemotaxis, phagocytosis, killing 4. fibrosis - fibroblast emigration and proliferation; deposition of ECM |
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What are the main cells involved in acute inflammation?
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neutrophils mainly (arrive within 24 hours) also involved are eosinophils and antibody mediated
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What are the main cells involved in chronic inflammation?
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mononuclear cells (monocytes) (lympocytes and plasma cells are also involved)
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What is chronic inflammation?
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persistent destruction and repair. Associated with blood vessel proliferatoin, fibrosis (scarring)
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What is an exudate?
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Type of edema you get in inflammation - consists of many cells, protein rich, specific gravity >1.020
due to: lymphatic obstruction, or inflammation have INCREASED vascular permeability |
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What is a transudate?
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hypocellular fluid, protein poor, specific gravity < 1.012
due to: increased hydrostatic pressure, decreased oncotic pressure, Na+ retention NORMAL vascular permeability |
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What mediators help a granuloma form?
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IL-2 and IFN-y (also involved in stimulating macrophages)
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What disease can form a granuloma? What is in a granuloma?
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epithelioid macrophages and giant cells (clump of many macrophages)
Fungal, Wegners, Sarcoid, Syphilis, Crohn's disease, Cat scratch (bartonella), Legoniella, Leprosy, Berylliosis |
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What are the possible resolutions for inflammation?
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1. restoration of normal structure
2. granulation tissue: highly vascularized, fibrotic (formed from connective tissue) 3. abscess formation: fibrosis surrounding pus 4. fistula - abnormal communication 5. scarring: collagen deposition resulting in altered structure and function |
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What are the steps in leukocyte extravasation?
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Rolling - tight adhesion - diapedesis - migration
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Rolling is mediated by what factors?
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siayl lewis X on the leukocyte and E and P-selectins on the endothelium
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Tight adhesion is mediated by what factors?
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(LFA-1) integrins on the leukocytes and ICAM-1 on the endothelium
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LAD1 is caused by a problem with what?
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integrin on the leukocyte - delayed falling off of umbilical cord
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What mediates diapedisis?
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PECAM-1 and endothelium and leukocytes - leukocytes squeezes through the endothelium
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What mediates chemotaxis (directing the leukocyte where to go)?
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CILK
C5a, IL-8, leukotriene B4, kallikrein |
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What is amyloid? What does an organ show if it has amyloid?
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abnormal protein folding of Beta pleated sheet demonstratable by apple-green birefringence of Congo Red stain under polarized light; affected tissue has a waxy appearance
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What are the different types of amyloidosis?
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Primary, Secondary, Senile cardiac, DM type 2, Medullary carcinoma of the thyroid, Alzheimer's disease, Dialysis-associated
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Primary amyloidosis
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AL protein, from Ig light chains: seen in diseases of plasma cell disorders (multiple myeloma, Waldenstrom's macroglobulinemia)
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Secondary amyloidosis
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AA protein, serum amyloid associated (SAA), protein: seen in chronic inflammatory diseases (RA, TB, Osteomyelitis, syphilus,leprosy)
*chronic tissue destruction leads to increased SAA |
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Senile cardiac amyloidosis
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transthyrtin protein - derived from AF (old foggies): minor deposits found at autopsy in the very elderly
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Diabetes mellitus type 2 amyloidosis
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Amylin protein derived from AE (endocrine): deposits in the islet cells
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Medullary carcinoma of the thyroid amyloidosis
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A-CAL protein derived from Calcitonin: see the amyloid deposits in the tumor
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Alzheimer's disease amyloidosis
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B-amyloid protein derived from amyloid precursor protein (APP): localized to chromsome 21
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Dialysis associated amyloidosis
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B2 microglobulin protein derived from MHC class I proteins: deposits in the joints of patients on hemodialysis for a long time (the protein is not readily filtered by the dialysis machine)
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What are the types of shock?q
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cargiogenic, hypovoluemic, septic, neurogenic
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Features of hypovoluemic/cardiogenic shock?
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Low-output failure, Increased TPR, Low cardiac output, Cold, clammy patient
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What are the features of septic shock?
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High output failure, decreased TPR, dilated arterioles, high mixed venous pressure, HOT patient
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What is shock?
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circulatory collapse with hypoperfusion and decreased oxygenation of the tissues
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What are the hallmarks of cancer?
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evading apoptosis (loss of p53), self-sufficiency in growth signals, insensitivity to anti-growth signals, sustainted angiogensis, limitless replicative potential, tissue invasion, and metastasis
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Hyperplasia
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Cells that have increased in number
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dysplasia
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abnormal proliferation of cells with loss of size, shape and orientation - it is reversible!
*often precedes malignancy |
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What is the progression of a neoplasm?
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normal - hyperplasia - dysplasia - carcinoma insitu - invasive carcinoma - metastasis
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Carcinoma in-situ
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Preinvasive - neoplastic cells have not invaded basement membrane
high nuclear/cytoplasmic ratio and clumped chromatin, neoplastic cells encompas entire thickness, tumor cells are monoclonal |
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Invasive carcinoma
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Cells have invaded the basement membrane using collagenases and hydrolases, can metastasize if they reach blood or a lymphatic vessel
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Metastasis
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spread to distant organs
must survive immune attack Seed and soil theory of metastasis seed: tumor embolus, soil: target organ (liver, lung, bone, brain) angiogensis allows for tumor survival decrease cadherin, increased laminin, increased integrin receptors |
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hyperplasia
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increase in cell number - reversible
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metaplasia
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change in cell type (1 adult cell is replaced with another) ex. squamous cell metaplasia in trachea and bronchi of smokers
*often secondary to irritation and/or enivornmental exposure REVERSIBLE |
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dysplasia
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abrnomal growth with loss of cellular orientation, shape, size in comparison to normal tissue maturation - often preneoplastic
REVERSIBLE |
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What are irreversible changes of -plasia?
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anaplaisa, neoplasia, desmoplasia
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What are reversible changes of -plasia?
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metaplasia, hyperplasia, dysplasia
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Anaplasia
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abnormal cells lacking differentiation; like primitive cells of same tissue, often equated with undifferentiated malignant neoplasms. Little or no resemblance to tissue of organ
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Neoplasia
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clonal proliferation of cells that is uncontrolled and excessive
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Desmoplasia
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fibrous tissue formation in response to neoplasm
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Grade vs. Stage
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Grade - degree of cellular differentiation based on histologic appearance of tumor
Stage - clinical assessment of the degree of localization (TNM) |
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Grade
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based on cellular differentiation, histologic appearance of the tumor. On a scale of I-IV based on degree of differentiation and number of mitoses per high power field - character of tumor itself
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Stage
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degree of localization/spread based on site and size of primary lesion, spread to lymph nodes, presence of metastasis; spread of tumor in specific patient
use TNM stagin |
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TNM
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T: tumor (size)
N: Node (spread to lymph node?) M: Metastasis |
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What has more prognostic value stage or grade?
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Stage
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What is the name for a benign or epithelium or mesenchymal tumor (often with name of tissue infront of it)?
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-oma (adenoma, papilloma)
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What is the name for a malignant epithelial tumor?
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-carcinoma (Adenocarcinoma, papillary carcinoma)
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What is the name for a malignant mesenchymal tumor?
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-sarcoma (angiosarcoma, leiomyosarcoma, rhabdomyosarcoma etc.)
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Hemangioma
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benign tumor, mesenchymal origin of the blood vessels
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Leiomyoma
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Benign smooth muscle tumor of mesenchmyal orgin
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Rhabdomyoma
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Benign skeletal muscle tumor of mesenchymal origin
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Osteoma
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Benign bone tumor of mesenchymal origin
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Lipoma
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Benign tumor of fat of mesenchymal origin
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Mature teratoma (in women)
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benign tumor of more than 1 cell line
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Immature teratoma and mature teratoma in men
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malignant tumor of more than 1 cell line
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adenocarcinoma, papillary carcinoma
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malignant epithelial tumor
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leukemia, lymphoma
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malignant blood cell tumor
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angiosarcoma
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malignant blood vessel tumor
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Leiomyoscarcoma
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malignant smooth muscle tumor
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rhabdomyosarcoma
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malignant skeletal muscle tumor
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Osteosarcoma
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malignant tumor of bone
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Liposarcoma
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malignant tumor of fat
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Characteristics of benign tumors
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well differentiated, slow growing, don't metastasis, well demarcated - can cause problems if they put pressure on near by structures
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Characteristics of malignant tumors
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may be poorly differentiated, fast growing, may metastazie, locally invasive/diffuse
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