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153 Cards in this Set
- Front
- Back
Squamous Metaplasia
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Bronchial epithelium of a smoker from columnar to squamous.
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Glandular Metaplasia
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(Barrett Oesophagus); squamous epithelium of oesophagus goes to columnar due to reflux.
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Dysplasia
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Disordered cell growth; a step towards malignancy.
1.) pleomorphism 2.) Enlarged, hyperchromic, irregular nuclei. 3.) Disordered arrangement/maturation. |
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Squamous Metaplasia
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Bronchial epithelium of a smoker from columnar to squamous.
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Glandular Metaplasia
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(Barrett Oesophagus); squamous epithelium of oesophagus goes to columnar due to reflux.
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Dysplasia
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Disordered cell growth; a step towards malignancy.
1.) pleomorphism 2.) Enlarged, hyperchromic, irregular nuclei. 3.) Disordered arrangement/maturation. |
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Mallory bodies
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Protein accumulations of cytokeratin filaments in hepatocytes.
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Russell Bodies
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Protein accumulation of Ig in plasma cells.
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α1-antitrypsin (abnormal type)
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Protein accumulation; a "permanently misfolded" protein that gets sequestered and accumulates in hepatocytes. Normally an acute phase reactant protease inhibitor.
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Lipofuscin
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pigment accumulation; sign of cell "wear and tear", from peroxidation of mem. lipids. Stains darkly with haematoxylin.
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Haemosiderin
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Pigment accumulation: aggregates of ferritin micelles due to ↑absorption, ↓usage, or ↑RBC degradation.
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Prussian Blue
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A stain that turns iron blue, used for visualising iron pigment accumulation in tissue slides.
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Congo Red
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A stain that distinguishes amyloid (pos.) from other hyaline substances like collagen and fibrin.
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S100-protein
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Marker for melanomas, 50% of malignant peripheral nerve sheath tumors, and clear cell sarcomas
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Reperfusion Injury
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Reoxygenation after ischemia may cause O2 free radicals, influx of neutrophils (who produce lytic enzymes and O2 free radicals). Causes lipid peroxidation of mems, modification of proteins, and DNA damage.
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Reversible Injury
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Hallmarks: hydropic change (influx of water), fatty change, ultrastructural alterations.
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Coagulative Necrosis
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Usu. caused by ischemic damage.
Denaturation > digestion; basic cell outline preserved as cell ghost. Cytoplasm: ↑eosinophilia Nucleus: pyknosis (shrinkage, ↑basophilia), karyorrhexis (fragmentation), karyolysis (loss of sustainable nuclear material). Ex: MI, Kidney infarct |
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Liquefactive Necrosis
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Enzymatic digestion > denaturation
Cells → viscous fluid. Ex: Bacterial infxn abscess, brain infarct |
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Caseous Necrosis
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Yellow-white, "cheesy" friable granular mass. Amorphous, eosinophilic, no cell outlines. Loss of tissue architecture. Epithelioid macs surround necrotic region. Multinucleated Giant cells may be present. A cell-mediated hypersensitivity.
Ex.: TB, histoplasmosis (fungal) |
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Fat Necrosis
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Lipases (from pancreas) released into abdominal cavity, releasing FAs from adipose. Causes saponification (FA combine with Ca2+).
Gross: Chalky white Hist: necrotic fat cells. Ex.: Pancreatitis, traumatic injury to adipose tissue. |
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Apoptotic Bodies
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Pieces of an apoptotic cell that break off, containing organelles and other components. Express new ligands for binding and uptake by phagocytes.
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Pro-apoptotic Factors
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Bax, Bak, Bad, Bik
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Anti-apoptotic Factors
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Bcl-2, Bcl-XL, A1
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Creatine Kinase MB
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An isoform of CK that's enriched in the cardiac myocyte mems. Presence in serum diagnostic of damage.
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Tissue Plasminogen Activator
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Clot-dissolving factor made by endothelial cells; levels highest in afternoons, lowest in the mornings (MIs likely), due to levels of inhibitor.
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Advanced Glycosylation End-Products (AGEs)
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A type of cumulative damage related to aging. Nonenzymatic glycosylation of proteins leads to AGEs that X-link cellular proteins (Maillard/Browning Rxn), occurs more freq. when [glucose] is high.
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Retinoic Acid
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Inhibits AP1, a TF that activates collagenases/elastases that degrade dermal matrix. AP1 is activated by UVB rays.
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Klotho
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mouse gene encoding a secreted β-glucosidase. Mice with homozygous deletion of this gene display progeria.
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Indy
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"I'm not dead yet"; fruit fly Kreb cycle intermediate transporter gene. Heterozygous loss of fxn doubles lifespan by ↓g met?
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Methuselah
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Fruit fly gene for G-protein coupled transporter. Loss of this gene ↑s resistance to oxidative stress, and lifespan by 35%.
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SGS1
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Yeast gene; heterozygous loss of fxn ↓s lifespan by 60%
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Cellular senescence
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Mortality of human cells; can divide ~50x max. Mediated by P53, which recognises exhaustion of telomere supply. Senescence is dominant and requires the nucleus.
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Crisis (in cell aging)
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When a cell runs out of telomeres, chr.s become unstable. Ultimately the cell stops dividing.
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histamin, bradykinin
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Chemical mediators in acute inflammation that cause contraction of endothelial cells, creating gaps and ↑g perm.
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IL-1, TNF, INF-γ
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Cytokines that reorganise cytoskeleton to produce endothelial gaps during inflammation.
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Vascular Endothelial Growth Factor (VEGF)
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Causes ↑'d transcytosis across endothelial cells during inflammation by putting in channels. Also ↑angiogenesis, endothelial cell prolf.
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Leukocyte Extravasation
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1.) Margination
2.) Rolling (selectins) 3.) Adhesion (Integrins; LFA-1, MAC-1) 4.) Transmigration (diapedesis): PECAM-1 5.) Interstitial Migration (chemotaxis): C5a, leukotriene B4, IL-8 |
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Myeloperoxidase
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Enzyme that makes H2O2 into reactive halide to kill bacteria in phagosomes.
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Fever cytokines
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IL-1
IL-6 TNF IFN prostaglandins |
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Plasma proteases
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1.) complement system
2.) kinin sys 3.) coagulation sys 4.) Fibrinolytic sys |
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Zeta Potential
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Negative charge of RBCs that is ↓'d by fibrinogen, γ-globulins etc., facilitating the formation of rouleaux, which sediment faster than monodisperse RBCs.
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Erythrocyte Sedimentation Rate (ESR)
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Measure distance RBCs sediment in a fixed time period (mm/hr). ↑'d sed rate is nonspecific evidence for inflammation.
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C-Reactive Protein (CRP)
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an opsonisation factor made rapidly by liver in response to inflammation; nonspecific lab marker, esp. of atherosclerosis.
CRP causes flocculation (precipitation) when mixed with capsular polysaccharide of pneumococci. |
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Serum Protein Electrophoresis (SPEP)
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Method used to measure changes in conc. of acute phase reactants and Igs to determine severity of inflammation or presence of "gammopathy".
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Acute Phase Reactants
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CRP: Oponsonisation (↑s 100-500x with inflammation)
Fibrinogen: coagulation α1-antitrypsin: protease inhibitor hatpoglobulin: binds Hb, forming biliverdin (eventually biliruibin) C3: complement Ceruloplasmin: binds copper α2-macroglobulin: protease inhibitor |
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Trichrome Stain
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Stains collagen blue; diagnostic of inflammatory ECM deposition due to fibroblast proliferation.
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Histamine and Serotonin
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Acute Inflam. mediators
Source: Histamine: mast cells, platelets. Serotonin: platelets. Effect: ↑vascular leakage. |
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Bradykinin
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Acute Inflam. mediators
Source: plasma substrate Effect: ↑vascular leakage, pain! |
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C3a
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Acute Inflam. mediators
Source: plasma protein via liver Effect: ↑vascular leakage, C3b is opsonic. |
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C5a
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Acute Inflam. mediators
Source: Macs Effect: ↑vascular leakage, chemotaxis of neutrophils. |
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Prostaglandins
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Acute Inflam. mediators
Source: Mast cells, mem. phospholipids. Effect: potentiates other mediators; vasolidation, pain, fever. |
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Leukotriene B4
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Acute Inflam. mediators
Source: Leukocytes Effect: Neutrophil chemotaxis. |
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Granulation Tissue
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On the 3rd day of healing, this tissue begins to form in wound space. Pink, soft, granular, mixture of BVs and fibroblasts laying down collagen in haphazard fashion (not parallel).
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Collagen Fibrils
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On day 5 of wound healing, fibrils begin to bridge the wound.
Fresh granulation: type III Day 7-8: Type I collagen 2-3 months: Max accumulation Evenutally fibres are reoriented along lines of stress. |
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Collagenous Scar
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By year 1 of wound healing, collagen has been re-organised into parallel strands, and the scar is hypovascular, hypocellular.
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Wound Contraction
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Feature of secondary union/intention of large, contaminated wounds. Mediated by myofibroblasts. Contraction starts 5 days post-injury.
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Labile Cells
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Continuously dividing tissue with stem cells; most capable of repair. Include epidermis, bone marrow, lymphoid tissue, and GI mucosa.
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Quiescent/Stable cells
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Little, if any replicative activity, but has potential to divide if stimulated. Include: hepatocytes, renal tubular epithelium, endocrine cells, endothelium, CT, bone, sm mm.
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Permanent Cells
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Cannto divide; if cell dies, it is replaced by CT. Ex: neurones, cardiac myocytes, sk mm. (Caveat: portion of the cell may regenerate).
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Type I collagen
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Most abundant form; found in bone, skin, tendon, fascia, and mature scars. Fibrillar
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Type II collagen
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Found in cartilage, nucleus pulposus, and vitreous body. Fibrillar
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Type III collagen
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Abundant in pliable organs such as BVs, uterus, GI tract, skin. Important in early wound healing. Fibrillar.
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Type IV collagen
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Found in BMs. Forms sheets.
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Elastic Fibres
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Very long half-life, provide recoil to tissue. Contains elastin and fibrillin, found in BVs, skin, lung, uterus (cf. Type III collage).
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Fibronectin
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Glycoprotei that binds other macromolecutes. Involved in migration, adhesion, stabilisation of early wound, opsonisation, chemotaxis (macs/fibroblasts)
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Proteoglycan
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Glycosaminoglycan bound covalently to proteins; like a sponge. Involved in ECM organisation.
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Basement Membrane
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Seperates cell from stroma, composed of Type IV collage, heparan sulfate proteoglycan, and Laminin.
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Thrombospondin
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Involved in cell-cell and cell-matrix binding, inhibits angiogenesis.
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IL-1
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Activates leukocytes, endothelium, ↑s adhesion molecules, fever. Acute phase cytokine.
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IL-8
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Source: Macs
Effect: Angiogenesis, chemotaxis |
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PDGF
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Effect: ↑IL-1 and bFGF, chemotaxis, collagen syn.
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EGF (epidermal GF)
aka TGF-α |
Effect: ↑cell division, angiogeneis.
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TGF-β (transforming GF)
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Effect: chemotaxis of macs and fibroblasts. ↑collagen syn., inhibits prolif. of certain cells.
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bFGF (basic fibroblastic GF)
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Effect: ↑cell division, angiogeneis. (same as EGF)
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Resolution
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Healing with restoration of normal structure and function, with little or no scarring. Requires stromal framework to be intact.
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Organisation
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Healing with loss of normal sxr and fxn, with marked scarring. Usu. due to prolonged infxn/inflam., sig. necrosis, destruction of stromal framework, or injury involving permanent cells.
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Hypertrophic scar
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Type of a scar characterised by excessive granulation, persistant collagen arranged in nodular whorls, but flatten spontaneously over 1+ years. Nodules eventually shrink and straighten out. Tends not to recur if excised.
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Keloids
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Scar of persistant collagen nodules that extend beyond site of original injury, and will rarely regress. Tends to recur if excised. Higher incidence in dark-pigmented individuals.
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Fibroplasia/fibrosis
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Profileration of fibroblasts in wound repair, resulting ind deposition of ECM.
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Transudate
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assoc. with noninflammatory conditions; fluid is an acellular ultrafiltrate with low protein content and low specific gravity (<1.015)
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Exudate
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Usu. associated with an inflammatory condition. Fluid has lots of cells and cellular debris, high protein content, and high specific gravity (>1.015)
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Active Hyperaemia
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↑'d volume of blood in tissue due to BV (arteriolar) dilation, mediatedy by neurogenic or chemical stimulation. Blood is more oxygenated than passive hyperaemia due to ↑'d inflow of blood.
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Passive Hyperaemia
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Congestion caused by impaired venous drainage and backing up of blood. Systemic (CHF) or localised (thrombosis). Blood more deoxygenated. "Nutmegging" of congested liver, necrosis of central lobules. Can result in atrophy, poor wound healing.
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Anticoagulants
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Prostacyclin (PGI2) [↓s platelet aggregation, vasodilator) thrombomodulin (regulates thrombin), tissue factor pathway inhibitor (TFPI)
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Tissue Plasminogen Activator (tPA)
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Profibrinolytics that is the first line of anti-clot therapy in most hosptials.
Made by endothelial cells. Converts plasmalogen to plasmin. Potentiated by fibrin, low at nigh. |
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von Willebrand factor (vWf)
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Procoagulant syn.'d by endothelial cells and megakaryocytes, stored in Webel-Palade Bodies (endothelial) and α-granules (platelets). Missing in classic haemophilia. high MW spp mediate platelet adhesion and factor VIII transport.
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Thromboxane A2 (TXA2)
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Mediates platelet aggregation. Released from platelets, whose COX-2 and PL systems cleave it from mem. phospholipids.
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dense granules
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found in platelets; contains ATP, ADP, serotonin, Ca2+, etc.
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α-granule
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found in platelets; contains fibrinogen, vWf, fibronectin, etc.)
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Aspirin (acetylsalicylic acid)
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irreversible inhibitor of COX-2, "anti-platelet". Lasts lifetime of platelet (7-10d), prolonging bleeding time.
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gpIIb/IIIa inhibitors
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anti-coagulative drugs that inhibit platelet mem. glycoproteins used as RR for adhesive plasma proteins (vWf, fibrinogen). Ex.: ReoPro, Integrilin.
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Intrinsic Clotting Pathway
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Activated by conact with clotting factors with negatively charged "activating" surfaces. Players: XII, XI, IX, VIII, kallikrein, HMWK.
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Extrinsic Pathway
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Believed to be initiated by "tissue factor" liberated from damaged extravascular tissue. Players: VII
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Factor XIII
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Transglutaminase clotting factor of the common pathway taht stabilises fibrin by catalysing cross-linking.
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Vitamin K-dependent clotting factors
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II (thrombin), VII (extrinsic), IX (intrinsic), X (common), protein C, and protein S
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Antithrombin (AT)
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Serine Proteinase Inhibitor (SERPIN) made in liver that inhibits all clotting factors save VIIa (extrinsic).
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Protein C
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Made by hepatocytes (mostly) and endothelial cells. Vit-K dependent; inhibits Va and VIIIa (intrinsic+common). Half-life is 5-10hrs, cf. VII.
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Protein S
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Made by hepatocytes and other cells; Vit.-K depenedent cofactor of Protein C, helping to inhibit Va/VIIIa. Free form is active. Bound inactive form is complexed to C4b-binding protein, an acute phase reactant. Thus, acute inflamm. increases clotting.
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Tissue Factor Pathway Inhibitor (TFPI) aka Lipoprotein-Associated Coagulation Inhibitor (LACI)
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Made by endothelium, binds to and inactivates Xa, then VIIa (extrinsic+common). If VIII and IX are present though, VIIa/tissue factor complex is protected from TFPI.
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Annexin V
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Cell-bound protein that seems to inhibit tissue factor (extrinsic)
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Warfarin (Coumadin)
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Anti-coagulating drug that prevents Vitamin K from being recycled to its reduced form, rendering it unable to help carboxylate factors II, VII, IX, X, protein C, and S.
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Heparin
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Highly sulfated linear glycosaminogglycan that binds to antithrombin, potentiating its inhibition of IIa and Xa.
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Citrate
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Only acceptable anticoagulant for test tubes. Chelates Ca2+, preventing clot until exogenous Ca2+ is added.
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Prothrombin Time (PT)
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Asseses the extrinsic and common pathways (VII), can monitor Warfarin therapy.
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Fibrin Degradation Product (FDP)
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Pieces of cross-linked fibrin broken up after fibrinolysis. Breakup is mediated by plasmin.
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Urinary-type Plaminogen Activator (aka urokinase, uPA)
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Converts plasminogen into active plasmin, like tPA. Source unknown, but abundant in urine. Potentiated by fibrin.
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Plasminogen Activator Inhibitor-1 (PAI-1)
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SERPIN like antithrombin. Inhibits tPA, high at night. Platelets are rich source. ↑ clotting.
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α2-Antiplasmin
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Inhibitor of plasmin, syn.'d by liver.
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Vitamin A
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Sources: green leafy vegetables, eggs, butter, meat, milk, fish liver.
Fxns: maintenence of specialised epithelia, enhance immunity, antioxidant, reg. cell growth. |
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Vitamin C
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Sources: citrus fruits, leafy green vegetables, peppers, tomatoes.
Fxn: powerful antioxidant, free radical scavenging. Keeps ferrous iron reduced for collage hydroxylation. |
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Vitamin E
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4 related tocopherols and tocotrienols; α-tocopherol most potent.
Sources: vegetables, grains and their oils, fish Fxn: antioxidant |
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Thiamine (B1)
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Source: unrefined foods.
Antithiamines: raw fish, strong tea, coffee. Fxns: ATP syn (oxidative decarboxylation), pentose phosphate pathway (transketolase), maintence of neural mems and normal nerve conduction. |
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oncogene
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Gene that causes cancer if "turned on" by being translocated into the transcription millieu of another more active gene. Ex.: abl gene, when under transcriptional control of bcr.
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mutator gene
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Gene in which loss of fxn leads to genomic instability and ↑ mutations. Participates in "two-hit" mechanism. Ex. hMSH2 gene of HNPCC
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tumour suppressor gene
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Gene which normally prevents overproliferation. Loss of fxn causes overproliferation and ↑ mutations. Participates in two-hit mechanism. Distinction from mutator gene unclear.
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K-ras
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Oncogene that binds GTP and participates in signal transduction. Gain-of-fxn produces protein with ↓'d intrinsic GTPase activity, thus longer GTP binding and ↑'d cellular proliferation.
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p53
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Classic tumour suppressor gene that prevents cells with unrepaired DNA damage from entering S phase, and stimulates transcription of DNA repair genes. Induces apoptosis in tumours that outgrow their blood supply. Dominant negative; even one mutated allele will result in nonfunctional dimer.
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dominant negative
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Loss of fxn in even one allele is enough for disease phenotype. Classic example is p53.
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Carcinoma-in-situ
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a tissue with all the characteristics of malignancy, but has not yet metastisised. Technically not yet cancer.
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E-cadherin
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Downregulation of this gene results in ↓'d cohesiveness of tumour cells.
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matrix metalloproteinases (MMP)
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Mediates degradation of ECM in tumour cells so they can invade.
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Intravasation
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entry of tumour cells into lymphatic or vascular vessels.
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Extravasation
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Circulating tumour cells enter distant tissue sites.
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Cetuximab (Erbitux)
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monoclonal Ab drug against EGFR (epidermal growth factor); some efficacy against metastatic colorectal cancer, targetting an oncogene.
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Bevacizumab (Avastin)
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humanised Ab against VEGF, ↓tumour-stimulated angiogenesis in colon cancer.
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N-myc
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oncogene that is activated by amplification in neuroblastoma.
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HER2/neu
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cell surface growth factor oncogene that is overexpressed in some breast/ovarian cancers
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BRCA-1, BRCA-2
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Mutator genes involved in repair of dsDNA, implicated in some familial breast/ovarian cancers.
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Rb (retinoblastoma) gene
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tumour suppressor gene involved in cell cycle checkpoint. Familia (two-hit) or somatic.
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NF-1
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Tumour suppressor gene; neg. regulator of Ras; del permits unchecked ras-induced proliferation and neurofibromatosis.
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Initiators
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factors that produce irreversible DNA damage but themselves don't produce neoplasms.
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Promotors
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Factors that can cause tumours in "initiated" cells (by stimulating cell proliferation, leading to further genetic damage)
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Direct-acting chemical carcinogen
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covalently modifies target molecule, typically DNA.
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Indirect-acting chemical carcinogen
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requires metabolic conversion to "ultimate carcinogen", which is direct acting.
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Anticancer alkylating agents
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Direct-acting carcinogens that can cause 2° iatrogenic malignancies such as leukaemia.
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Polycyclic aromatic hydrocarbons
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Chemical carcinogens including tobacco smoke, smoked meats, broiled animal fat.
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Aromatic amines/azo dyes
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Chemical carcinogens found often in dye and rubber industry, causing bladder cancer.
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Nitrosamines
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Chemical carcinogens that cause GI cancer
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Vinyl chloride
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chemical carcinogens that cause liver haemangiosarcoma.
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chromium/nickel
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chemical carcinogens that cause lung cancer.
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UV light
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forms pyrimidine dimers in skin, causing squamous cell and basal cell carcinoma, and malignant melanoma.
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Human Papillomavirus
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DNA oncogenic virus whose protein product inactivates p53, causing uterine, cervical, anogenital, oral, and laryngeal cancers.
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Epstein-Barr Virus (EPV)
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DNA oncogenic virus that has B-cell mitogenic effects; linked to Burkitt's Lymphoma.
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Hepatitis B virus
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DNA oncogenic virus associated with hepatocellular carcinoma. Viral protein HBx inhibits p53
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Kaposi sarcoma herpesvirus (KSHV), aka human herpesvirus type VIII
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DNA oncogenic virus associated with Kaposi sarcoma and B-cell lymphoma in HIV pts. Virus encodes homologues of human GFs.
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Human T-cell Leukaemia Virus Type 1 (HTLV-1)
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RNA oncogenic virus associated with T-cell leukaemia/lymphoma and tropical spastic paraparesis (deymyelinating disorder). Virus induces IL-2 and IL-2 R, causing polyclonal proliferation of T-cells. In small cases, T-cells progress to monoclonality and malignancy.
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Hepatitis C virus
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RNA oncogenic virus that ↑s risk of hepatocellular carcinomas due to chronic cirrhosis triggering cellular proliferation.
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Helicobacter pylori
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Oncogenic gram neg spiral/rod bacteria associated with large percentage of gastric lymphoma; may stimulate proliferation of B-lymphocytes.
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Grading
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extent to which a malignant neoplasm resembles normal tissue; "well-differentiated" to "poorly differentiated".
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Staging
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extent of spread of cancer, independent of grading. Codified by TNM system (Tumour size, Node involved, Metastases)
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Tumour Markers
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PSA - prostate cancer
CEA - GI, breast cancer AFP - liver, germ cell cancers CA 125 - ovarian cancer hCG - trophoblastic/germ cell tumours |
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Asbestos/Feruginous body
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Asbestos fibres coated by iron-protein complex, characteristically found in asbestosis. Caused by Macs engulfing asbestos and dying. Fe then attaches to asbestos.
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Aflatoxin B1
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Product of Aspergillus Flavus; contamination of food by fungus; peanuts/grains esp. Metabolism of Aflatoxin B1 yields reactive electrophilic epoxide, covalently binds to DNA; tumour initiation. HBV may be synergistic.
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