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93 Cards in this Set
- Front
- Back
What are pesticides? benefits? risks? What is it regulated by?
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-chemicals used to destroy undesireable pests or plants
-improved crop yield and eradication of vector borne diseases -human fatalities and long term toxicity -environmental contamination -biomagnification (lipid solubility) -translocation by vaporization, drift, water supply -federal insectiside, fungicidal, rodenticide act -nemanticides, plant growth regulators defoliants, desiccants addes in 1951 and 1961 -administrative authority turned over to EPA in 1972 |
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What can exposure to pesticides may result in?
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-neurotoxicity
-reproductive effects including endocrine systems (endocrine disruptors) -teratogenic effects -carcinogenic and oncogenic effects -mutagenic effects -hematological effects including anemia -immunological effects including suppression and activation -transgenerational effects |
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What are insecticides?
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-essentially chemicals attacking the neurotransmitter receptors, ion channels, and related enzymes in insects
-nicotinic receptors aree also present in humans, insecticides cause toxcitiy in humans |
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What are organochlorines as insecticides? Acute and chronic effects?
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-low volatility, chemically stable, lipid soluble, slow rate of biotransformation and degradation
-estrogenic and enzyme-nducing effects interfere directly or indirectly with fertility and reproduction -acute toxicity associated with CNS disturbances -chronic toxicity manifests as hepatic hypertrophy, centrilobular necrosis, hepatic tumors -toxicity involves CNS and PNS hypersensitivity due to prolonged negative afterpotential -chlornated cyclodiene, benzene, cyclohexane, inseticide toxicity characterized by CNS hypersensitvity -high lipid solubility, slow metabolism promotees extensivee and prolonged stoage of insecticides |
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What are proposed sites of action of DDT (insecticide)?
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-reducing potassium transport through pores
-inactivating sodium channel closure -inhibiting sodium-potassium and calcium-magnesium ATPases -calmodulin-calcium bid=dning with release of neeurotransmitter |
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What are proposed sites of action of cyclodiene-type insecticide?
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-chlorine ion transport by nhibiting GABA receptors on the chloride channel as well as inhibition of Ca, Mg-ATPase
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What are anticholinerative insecticides? symtoms ot toxicity? Delayed toxicity?
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-organophosphorus esters (parathion,paraoxon) and carbamate esters
-symptoms of poisons are due to cholinestrase inhibition -muscarinic symtpoms: tightness in chest, wheezing, saliva -nicotinic symtoms:involuntary twitching, hypertension CNS symptoms: anxiety, restlessness, insomnia -death due to asphyxia scondary to respiratory failure -delayed neurotoxicity: seen with organophosphorus esters but not carbamate esters |
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Where do organophosphorus and carbamate esters bind to as in active site of enzyme?
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-hydroxyl group
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What are pyrethroid insecticides?
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-compounds extracted from pyrethrum or chrysanthemum floweres
-rapid paralytic action on flying insects despite low toxicity in insects and mammals due to efficient metabolism |
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What are possible sites of action for pyrethroid insecticides?
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-GABA inhibitor which also innhbiits chlorine intake
-Ca/MG ATPase for efflux of calcium |
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How do you classify herbicides?
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-by application time and method (preplanting, preemergent, postemergent)
-mechanism of toxicity (selectve, contact, translocated) |
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What is the mechanism of action of Ureas, 1,3,5-triazines, etc.?
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-inhibiton of photosynthesis by disryption of light reactions and blockade of electron transport
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What is the mechanism of action of dinitrophenols and halophenols?
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-inhibition of respiration by blockade of electron transfer from NADH or blocking thee coupling of electron transfer to ADP to for ATP
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What is the mechanism of action of aryloxyalkylcarboxylic acids and benzoic acids?
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-growth stimulents
-auxins |
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What is the mechanism of action of alkyl N-arylcarbamates?
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-inhibitors of cell and nucleus division
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What is the mechanism of action of chloracetamide, o-substituted diphenyl ethers and hydrazines as an herbicide?
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-inhibition of carotenoid synthesis
-protective pigments in chloroplasts to prevent chlorophyll from being destroyed by oxidative reactions |
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What is the mechanism of action of S-alkyl dialkylcarbamodithioates and aliphatic chlorocarboxylic acids as an herbicide?
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-inhibiton of lipid synthesis
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What are chlorophenoxy compounds as herbicides?
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-auxins- stimulate growth in plants
-TCDD (dioxin)- carcinogenic,teratogenic and immunosuppresant for humans -agent orange: combination of n-butyl esters of 2,4-D and 2,4,5-T contaminated with TCDD |
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What are biochemical effects of TCDD on humans?
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-enzyme induction--> altered metabolism
-modulation of hormones and receptors--> altered homeostasis -modulation of growth factors and receptors--> altered growth and differentiation |
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What is the molecular mechanism of action of dioxin-like chemicals to activate AhR-dependent gene expression?
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-enters cell and binds to AhR gene expressing compound, which is also bound to protein hsp90
-the proteins undergo tranformation and the chemical is translocated into the nucleus and binds to DRE's, ARNT's -once expressing P4501A1, mRNA expresses new polypeptides which leades to toxicity |
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What are bipyridals as herbicides (paraquat, diquat)?
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-pulmonary toxicants
-conduct lipid peroxidation |
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What are the various properties of solvents?
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-exposure
-frequency of exposure -toxicity |
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How is exposure a property of solvents?
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-volatile solvents present as vapors (route of entry via respiratory system and penetration into systemic circulation via diffusion)
-partition coefficient affects toxicity onset time -percutanous route of entry includes local irritation and affects integrity of skin barrier |
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How is frequency of exposure a property of solvents?
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-consumer vs occupational exposure
-standarization includes threshold limit value, time-weighted average, and short term exposure limit -regulation is by OSHA and NIOSH |
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How is toxicity a property of solvents?
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-involves central nervous system
-disorieentation progression to loss of consciousness -respiratory or cardiovascular collaspe -physical interaction between solvent and cells of CNS -organ specific toxicities of some solvents due to repeateed exposure to tolereable lvls of solvents -can cause metabolic bioactivation (species difference in p450 enzymes) -based on saturation kinetics (partition coefficient and lipphilicity) |
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How is benzene a toxic solvent?
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-sources include steel production, fuel, and solvent for rubber and inks, also starting material for chemical synthesis
-acute toxicity includes CNS depression leading to unconsciousness and death -has hematopoietic toxicity including aplastic anemia and acute myelogenous leukemia -caused by benzene metabolites |
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What detox pathway can help against benzene toxicity?
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-glutathione
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How is chloraform and carbon tetrachloride toxic solvents?
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-reversible hepatoxicity
-nephrotoxicity -forms free radicals for lipid peroxidation and covalent binding |
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How is ethyl alcohol a toxic solvent?
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-TLV= 1000ppm
-legal intoxication= .8mg/100mL -metabolism will reduce blood alcohol by 15-20 % per hour -general anethetic and nutrient for CNS -can cause fetal alcohol syndrome (mental deficency and microcephaly) -alcohol metabolism by alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 |
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How is methanol a toxic solvent?
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-retinal toxicant causing reversible or permanent blindness
-methanol becomes formaldehyde, then formic acid then CO2 during metabolism by catalase peroxidative and alcohol dehydrogenase pathway |
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How is ethylene glycol and propylene glycol toxic solvents?
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-ethylene glycol is antifreeze
-metabolized by alcohol dehydrogenase then aldehyde oxidase to beocme oxalic acid -proylene glycol is additive in food and cosmetics -metabolized by same enzymes to become pyruvic acid -used in lacquers, varnishes, resins, printing ink,, textiledyes, and gasoline additives -can cause reproductive toxicity |
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What is the molecular pathway of Rhodanese activity with cyanide?
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-thiosulfate group reacts with thiol group on cysteine-247 to form a disulfide
-it then reacts with cyanide to produce thiocyanide then converts back to normal thiol |
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How is rhodanese enzyme activity important?
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-important in the contamination of cyanide since thiocyanate formed is relatively harmless
-the use of thiosulfate solution as an antidote for cyanide poisoning is based on the activation of this enzymatic cycle |
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What is the route of metals in the environment for potential toxicity?
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-metal emission goes to either the atmosphere and/or with fallout/washout goes to terrestial systems (with runoff/irrigation), lakes/rivers (with flow), yo estuaries (with mixing), to oceans
-from there to sediments and specimens |
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What are the various areas of exposure for metal toxicity?
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-metals from the air can get into the respiratory tract
-metals in food, water, and drugs can get into the GI-tract -metals can also get on the skin -eventually circulates around the blood and passes through the kidneys and liver -then gets excreted by sweat, hair, urine, and feces |
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What is cellular uptake of metals?
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-soluble metal compounds taken through cellular ion channels and transporters
-particulate metal compounds taken in by phagocytosis -metal compound may be reduced and bind to proteins inside cells -mechanism of toxicity depends on metal species |
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What does metal toxicity depend on?
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-length of exposure time
-concentration -and type of metal species |
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What is the biological half-life of metals?
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-short (arsenic)
-long (cadmium) -due to specific tissue retention |
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What does cellular target of metals depend on?
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-metal species and lipid solubility
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What are indicator tissues for recent exposures? long term?
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-blood, urine (except for cadmium)
-hair |
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What factors influence toxicity of metals?
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-interactions with essential metals
-formation of metal-protein complexes -age and stage of development -lifestyle factors -chemical form or speciation -immune status of host |
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What metals are carcinogenic for humans?
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-arsenic
-beryllium -cadmium -hexavalent chromium -nickle compounds |
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What metals are carcinogenic to animals?
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-arsenic
-beryllium -cadmium -hexavalent chromium -dextran -inorganic lead -inorganic mercury chloride -metallic and compound nickel |
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What are metals in carcinogenesis? What are various mechanisms?
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-metals act as carcinogens or co-carcinogns involving:
-interferance with cellular redox systems and oxidative stress -inhibiton of DNA repair causing mutations -deacetylation leading to gene activation and methylation leading to gene silencing -deregulation of cellular prolifereation control by induction of proto-oncogens, inactivating p53 and apotosis signals -can bind directly to DNA (Chromium) -cna have specific interactions with proteins |
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What metals can cause chelation?
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-natural chelators:
-metallothionine by cadmium, insulin by zinc, hemoglobin by iron, mRNA by Mn, antibiotics by magnesium, and enymes by sulfhydral groups -EDTA: Ca++ form not Na+ -BAL and derivatives -microbial products: penicillamine and desferrioxamine -dithiocarbamates for Nickel or cadmium |
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What is lead toxicity? neurological? peripheral? hematological? Renal? cardiovascular? endocrine? carcingenicity?
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-neurological: cognitive, IQ, neurodevelopment, neurotransmitter release, disrupts tight junctions, replaces calcium, affects Na-K-ATPases
-peripheral neuropathy by demyelation and schwann cell degeneration -hematological: anemia, erythrocyte maturation and shortened lifespan and impaired heme synthesis by inhibiton of porphyrin incorportation -renal effects: inhibit proximal tubule function -cardiovascular: hypertension -endocrine effect: affects male reproduction -carcinogenicity: shown in animal models but not in humans |
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What is mercury toxicity?
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-target organ depends on chemical species:
-inorganic salts go to kidney -organic salts go to CNS -vapor goes to CNS -has high affinity for thiol group in enymes -can cause parethesia, ataxia, dysarthria, deafness and death |
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What is cadmium toxicity?
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-important contaminant in environment (industry and seafood)
-may be inhaled through some cigarettes -calcium or iron deficiency enhances cadmium absorption -competes for zinc uptake -retained in body (bone) for a long time (bone pain and fragility) -major acute target is kidney -complexes with metallomethionine (produced in the liver) -teratogenic and carcinogenic (testicular, prostate) |
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What is arsenic toxicity?
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-a classic poison, many chemical forms used in pesticides, etc.
-a concern in drinking water as mineral water of volcanic source -target tissues include GI, skin, neurotoxicity (central and peripheral), and respiratory system -carcinogenic (skin, lung) and teratogenic -high affinity for thiol group -use BAL treatment as antidote |
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What is beryllium toxicity?
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-important industrial metal (alloy, ceramic)
-tissue target is lung (berylliosis and cancer) -immune toxicity includes contact dermatitis and delayed hypersensitivity |
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What is chromium toxicity?
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-multiple valence forms
-cofactor for insulin -glucose tolereace factor -renal toxicity and cancer for respiratory tract |
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What is nickel toxicity?
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-deficency causes anemia (iron absorption)
-immunogenic (contact dermatitis from jewlery and causes lung and nasal cancers) |
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What is cobalt toxicity?
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-essential component in vitamin B12
-causes cardiomyopathy and polycythemia |
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What is copper toxicity?
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-cofactor in many enzymes such as SOD, cytochome oxidas, and catalase
-can casue abnormal organ development |
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What is iron toxicity?
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-in hemeglobin
-excessive uptake may occur in use eof iron pots, frequent blood transfusion -results in accumulation of iron storage sites (ferritin and heemosiderin) -deficency causes increase in transferrin |
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What is manganese toxicity?
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-cofactor in enzymes and RNA
-inhalation of Mn causes pneumonitis and CNS damage (parkinsons?) |
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What is selenium toxicity?
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-cofactor for enzymes such as glutathione peroxidase
-excess produces CNS toxicity |
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What is atrophy?
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-decrease in cell size or number in a tissue, organ, or part
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What is hypertrophy?
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-increase in cell size, both physiologic and pathologic
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What is hyperplasia?
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-increase in cell number, both physiologic and pathogenic
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What is metaplasia?
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-change in cell phenotype, more often pathogenic
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What is dysplasia?
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-failure to differentiate completely and normally, usually pathologic
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What is anaplasia?
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-failure to differentiate (to an adult phenotype), a criterion of malignant neoplasm
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What is neoplasm?
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-tissue (mass) resulting from abnormal cell growth, tumor in lay term
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What is neoplasia?
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-the process of neoplastic growth
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What is benign neoplasm?
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-a neoplasm growing localy
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What is malignant neoplasm (cancer)?
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-a neoplasm that invadees and/or metastasizes
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What is invasion?
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-growth into surrounding tissues, traversing normal tissue boundary
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What s metastasis?
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-growth of cancer cells at a second, separate sites, involving spreading by the circulation
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How do you diagnose neoplasms?
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-gross examination: lumps, bumps, ulcer...
-imaging: x-ray, CT scan, ultrasound, MRI, PET -blood sampling: PSA, TNF... -histological examination by brush cytology, needle biopsy and incisional and dissectional biopsy |
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What is the pathology of neoplasm?
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-each type of neoplasm has a characteristic behavior with some variation
can be benign or malignant |
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What is the nomenclature of neoplasms?
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-indicating cell origin and suggesting malignancy
-benign ends in -oma: adenoma,fibroma... -malignnat ends in carcinoma ot sarcoma: adenocarcinoma,, leimyosarcoma... -exceptions include melanoma, glioma, and astrocytoma |
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What is a carcnoma?
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-tumors derived from epithelial cells including squamous cell carcinoma, adenocarcinoma (gladular), urothelial carcinoma
-most common cancer type and reprsnts 80-90% of all cancer cases |
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What is lymphoma/leukemia?
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-cancers of bone marrow derived cells (lymphoma) or white blood cells (leukemia)
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What is sarcoma?
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-tumors derived from mesenchyma tissues such as muscle bone, cartilage, fat, and fibroblast
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What is differentiation of tumors?
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-refers to extent to which tumor cells resemble comparable normal cells, both morphologically and functionally
-benign tumors are generally well differentiated -malignant tumors range from well differentiated to anaplastic -have cellular and nuclear pleomorphism -high nuclear to cytoplasmic ratio -hyperchromatic straining -more mitoitc cells -tumor giants cells |
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What is the rate of growth of tumors?
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-most benign tumors grow slowly whereas most cancers grow rapidly
-tumor growth rates are correlated with their level of differentiation -with significant variations dependent upon body hormone lvls, tissue blood supply, and many unknown factors |
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What is local invasion of tumors?
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-nearly all benign tumors grow as cohesive and expandive masses that remain localized to their site of origin
-most benign tumors are encapsulated ina rim of compressed connective tissue, calleed fibrous capsule, that separates them from the host tissue -growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue -most cancers are poorly demarcated from the surrounding normal tissue |
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What is metastasis of tumors?
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-tumor implants discontinuous with primary tumor
-only malignant tumors do this -some exceptions are gliomas and basal cell carcinomas -conducts direct seeding of body cavities and surface -goes to lymphatic channels -goes to blood vessels |
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What is the pathway of tumor metastasis?
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-primary tumor formation
-localized invasion -intravasation -transport through circulation -arrest in microvessels of various organs -extravasation -formation of micrometastasis -colonization-formation of macrometastasis |
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What is grade and stage of tumors?
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-grade indicates degree of tumor cell differentiation
-stage indicates extent of invasion adn metastasis |
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What are the vasrious grades of tumor differentiation?
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-grade 1- well differnetiated
grade 2-moderatly grade 3- poorly grade 4- anaplastic |
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How do you make Paraffin-embedded sections for histological slides?
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-tissue sampling
-fixation -tissue processng (dehydration in alcohol, clearing with xylene, and embedding in paraffin) -sectioning -staining |
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How do you make frozen sections for histological slides?
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-Tissue sampling
-Tissue processing (embedding in OCT medium) -Sectioning -staining |
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How do you do Hematoxylin and eosin (H & E) staining?
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-Most common staining to show cellular components
• Hematoxylin, being a basic dye, has high affinity for the nucleic acids of the cell nucleus and stain the nucleus in blue. • Eosin is an acidic dye with affinity for cytoplasmic components (mainly proteins) and stain the cytoplasma in pink. |
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What is the epithelium?
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Derived from ectoderm, endoderm, or mesoderm
• Avascular cellular layer lining free spaces (lung, digestive tract) • Responsible for more than 80% cancer incidences • Classification based on architecture or relationship to other epithelial cells -includes a single or stratefied epithelium |
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How do you classify epithelium?
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-squamous
-cuboidal -columnar -transitional |
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What are Collective (mesenchymal) Tissues?
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• Connecting and anchoring tissues; providing support, strength,
insulation and protection to other tissues and organs of the body. • Derived from mesoderm. • Producing extracellular matrix including various fibrous proteins (fibronectin, collagen etc.) -fibroblasts and adipose tissues |
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What is hypertrophy?
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1.Increase in cell size, resulting in an increase in the
size of the organ, both physiologic and pathologic. 2.Generally involving non-dividing cells such as skeletal and cardiac muscle cells. 3.Reversible |
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What is hyperplasia?
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1.Increase in cell number, resulting in an increase in
the size of the organ, both physiologic and pathologic. 2.Generally involving dividing cells and often occurring with hypertrophy. 3.Reversible |
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What is metaplasia?
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• A reversible change in which
one adult cell type is replaced by another type. • The most common epithelial metaplasia: columnar to squamous. |
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What is dysplasia?
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failure to differentiate completely
and normally , usually pathologic. |
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What is anaplasia?
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failure to differentiate (to an adult
phentype), a criterion of malignant neoplasm. |