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112 Cards in this Set
- Front
- Back
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Define: pathology
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Pathology is the study and diagnosis of disease
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Define: etiology
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Cause of disease - 1. intrinsic, 2. genetic, 3. acquired
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Define: pathogenesis
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Mechanism of its development
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Define: morphology
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Structural alterations
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What are the causes of atrophy?
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1. ↓ workload(disuse b/c of a cast), 2. ischemia (sickle cell disease), 3. lack of hormonal/neuronal signaling(deinnervation), 4. malnutrition, 5. aging
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Define: clinical significance
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Functional consequences of morphological changes
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What cells are non-replicating?
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1. Brain, 2. heart(senile atrophy)
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Define: atrophy
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↓ in size and function of a cell
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Define: hypertrophy
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↑ in size and function
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What are the causes of hypertrophy?
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↑ mechanical demand - 1. Physiologic - striated muscles in weight lifters, 2. Pathologic - cardiac muscle in hypertension; ↑ endocrine stimulation - 1. ↑ breast size during lactation, 2. gravid uterus (estrogen), 3. puberty (growth hormone)
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What is the mechanism of hypertrophy?
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1. ↑ growth factors, 2. ↑ gene expression and protein synthesis
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Define: hyperplasia
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↑ in the number of cells in organ in tissues (not bigger); Right kidney is larger then the left b/c of more cells
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What cell types does not undergo hyperplasia?
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1. Nerve, 2. heart, 3. skeletal muscle
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What are the physiologic causes of hyperplasia?
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1. Breast development (puberty), 2. compensatory (hepatectomy - removed half liver), 3. antigenic stimulation (lymphoid)
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Define: metaplasia
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Reversible conversion of one cell type to another - squamous cells -> columnar cells (lower esophageal sphincter) (GERD- acid reflux-> squamous cells -> columnar cells that line the stomach -> produce mucous -> neutralize acid- disease = barratos esophagitis)
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What are the Pathologic causes of hyperplasia?
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Prostate (BPH - aging) - peeing out dust
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What is the reason for atrophy?
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To conserve energy b/c if u don’t need to use it then u want to save it
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What is the cause of bronchial squamous metaplasia?
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Irritation to tobacco smoke
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What is a disease of metaplasia from squamous cells to columnar cells in the esophagus?
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Barrett's esophagus -> may lead to cancer
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What is the MOA of metaplasia?
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Reprogramming of stem cells into more protective cells
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Define: dysplasia
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Disordered cell growth - usually epithelial cells exhibit uniform size, shape, nucleus, arranged in regular fashion thus dysplasia = defect in these
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Why is dysplasia bad?
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Precursor to cancer - not adaptive cells
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On a histological slide what does dysplasia look like?
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Cells that normally line up left to right are now lined up and down (ie not the same direction as its supposed to be)
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What is the main etiology of reversible cell injury
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1. ↓ oxidative phosphorylation, 2. ↓ ATP (↓ blood flow), 3. cellular swelling (injured cell)
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What causes a shift form reversible cell injury to irreversible cell injury
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No clear cut event just one or the other
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What are the 2 types of cell death
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Necrosis + apoptosis
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Define: necrosis
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Always pathological cell death -> cell damage so severe cell membrane is disrupted -> lysosomal contents leak out and digest cell; destroyed cell membrane -> troponin, CK, necrosis in the heart = MI
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Define: apoptosis
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Nuclear dissolution w/o complete loss of membrane integrity; intact cell membrane + hyperchromatic
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How do u get tissue hypoxia?
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Go from environment from 20%-> 10% (house fire)
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Define: hypoxia
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Deficiency of oxygen -> causes cell injury via reduced aerobic oxidative respiration(not the same as ischemia which is reduced blood supply)
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If u have ischemic injury vs hypoxic injury which is more severe
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Ischemic = more sever b/c hypoxic u r still delivering blood and nutrients, ischemic injury u not only stop the blood but u stop the flow of nutrients too
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What is the most important place of cell injury?
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Mitochondrial injury -> thus cell ↓ ATP -> loss of cell membrane integrity, ↓ protein synthesis
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What does a Na/K ATPase failure cause?
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1. Entry of Na+ into cell, 2. K+ efflux, 3. cell swelling, 4. dilation of ER
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DVT -> ↓ blood supply to muscle
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↓ in nutrients + ↓ O2 delivery -> cell ↓ ATP production -> ↓ Na/K ATPase -> entry of Na+ into cell/K+ efflux -> accumulate ions inside the cell b/c of the 3/2 ratio -> osmolality in cell ↑ -> moves water into cell(cellular swelling) -> ↓ Ca2+ pump -> cant put Ca2+ back into SR thus sucks more H2- into cell
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What is the very first sign of ↓ blood supply to muscle
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Cellular swelling (↓ Na/K ATPase)-> ↓ glycogen/glucose stores(anaerobic)-> lipid byproducts formed (causes cell to be opaque/cloudy)
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Under anaerobic conditions how fast do u need to produce ATP?
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18 fold needed anaerobic -> utilize glucose in the blood -> thus ↓ blood glucose -> ↓ glycogen
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Hydropic
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Water accumulation
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Dystrophic calcification
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If ionized Ca2+ ↑ in the area b/c of necrosis-> over times calcifies -> white hard substance
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Pt w/ heart attack -> 10yrs later heart attack-> 10 yrs later dies, what do u c?
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2 white spots - b/c calcification occurred over time -> calcification in the heart (calcification is not reversible)
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atherosclerosis
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Occurs overtime
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What does mis-folded proteins trigger?
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Unfolded protein response -> cell injury -> death
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What happens to the mitochondria during ischemia?
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↓ oxidative phosphorylation -> ↓ ATP -> ↓ Na+ pump (edema) + ↑ anaerobic glycolysis (↓ glycogen/↓ pH) + ↓ protein synthesis/lipid deposition
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What causes the mitochondrial damage?
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Ischemia -> ↑ Ca2+ (caused by inhibition of Ca2+ ATPase b/c lack of O2) -> cytochrome C release -> causes cell to go from reversible injury to irreversible injury
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What does the mitochondria damage release into the cell?
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Cytochrome C - integral component of ETC -> triggers apoptosis in cytosol
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What does the cytosolic Ca2+ do to the cell?
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↓ ATP, ↓ phospholipids, disruption of membrane and cytoskeletal proteins, nucleus chromatin damage, ↑ mitochondrial permeability (efflux of cytochrome C out of the mitochondria)
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What products are made during ROS damage?
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1. Lipid peroxidation (vitamin E stops this), 2. protein(leads to protein fragmentation), 3. nucleic acids (leads to lesions in DNA)
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What are the causes of ROS damage?
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1. Radiation, 2. chemicals, 3. ischemia-reperfusion, 4. aging, 5. microbial killing
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What are the ways to eliminate ROS
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Superoxide dismutase, glutathione(cytosol), catalas, binding transition metals (transferrin, ferritin, lactoferrin, and ceruloplasmin), vitamine ACE
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What happens if u damage catalase, superoxide dismutase
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Cell is sensitive to oxygen
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breath 100% oxygen
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↑ activity of oxygen scavenging enzymes ->
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Ischemia -> coronary artery thrombosis, diaphoretic, pain in arms, enzymes and EKG normal, clot busting enzymes -> re-establish blood flow -> patient gets worse, why
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When heart becomes ischemic -> wait days -> ↓ activity of oxygen scavenging enzymes -> ↑ O2 supply to tissues by giving clot busting -> oxygen radicals are now far in excess b/c ↓ activity of oxygen scavenging enzymes = reperfusion injury
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What is the effect of ROS on lipids?
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ROS + lipid -> unesterified Free fatty acids (acyl canitine, lysophospholipids ↑ in injured cells ) -> has a detergent effect on membranes -> ↑ permeability and electro physiologic changes -> influx of ions -> edema
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When does a cell die?
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1. Failure to reverse mitochondrial dysfunction, 2. membrane dysfunction, 3. leading to cell death, 4. massive leakage of intracellular material into extracellular space + massive influx of Ca2+ into cell
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Is cellular swelling a reversible event? Is fatty changes reversible?
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Yes, yes
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What happens when u see two white spots in the left ventricle?
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Pt has 2 previous MI b/c of dystrophic calcification occurred (accumulation of Ca2+)
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What happens in an MI when the intracellular debris is floating around too long?
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It causes dystrophic calcification -> debris attracts calcium salts and other minerals -> leads to cacification
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What happens when u see karyolysis, pyknosis, karyorrhexis?
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Associated w/necrosis
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Karyolysis
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Faded basophilia
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Pyknosis
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Nuclear shrinkage
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Karyorrhexis
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Fragmentation
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What is the morphology of necrotic cells?
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1. "glassy" appearance, 2. "myelin figures" -> dead cells replaced by whorled phospholipid masses -> FA residues -> calcification of residues -> clacium soap generation, 3. nuclear changes -> DNA break down
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What are the types of necrosis?
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1. Coagulative, 2. liquefactive, 3. gangrenous, 4. caseous, 5. Fat, 6. fibrinoid,
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What is the most common type of necrosis?
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Coagulative necrosis - due to blockage of blood flow (thrombus) -> tissue becomes necrotic due to HYPOXIC cell death
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Liquifactive necrosis
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Thrombis -> HYPOXIC cell death of the BRAIN-> turns to liquid b/c it died
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Gangrenous necrosis
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Thrombus in leg -> undergoes coagulative necrosis -> now gets bacterial infection -> new undergoes Liquefactive necrosis(ie coagulative + bacteria + Liquefactive)
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Caseous necrosis
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Necrosis involving lung = usually TB infection NO MATTER WHERE THE INFECTION IS - ie TB meningitis even though its in the spinal cord its caseous necrosis; "Cheesy" white appearance of area of necrosis w/ granulomatous border
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Fat necrosis
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Usually w/pancratitis or breast tissue blunt force trauma(fat destruction)
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Fibrinoid necrosis
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Necrosis of medial portion (smooth muscle) of blood vessel itself(immune complexes -> form "smudgy" eosinophilic deposits); seen in renal vascular malignant hypertension
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What is the problem in ischemic-reperfusion injury?
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Initially there was an ischemia -> leads to ↓ O2 in tissues -> ↓ antioxidents -> thus when u bring back the blood flow u ↑ O2 in tissues and ultimately generating ROS -> injuring tissues
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What chemical induces injury on contact?
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Mercuric chloride (HgCl2) poisoning -> binds to cell membranes -> ↑ permeability -> inhibits ATPase dependent transport
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What chemical converts non-biological active compound to reactive toxic metabolites?
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CCl4 (dry cleaning industry) -> P-450 -> converts to CCl3 (highly reactive) -> leads to fatty liver -> swelling -> membrane changes
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Why is acetaminophen bad in alcoholics?
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Metabolized in liver by cytochorme P450 mechanism -> produces small amounts of free radicals -> normaly clear -> if u OD on tylenol + alcoholic -> jaundice -> produced so much metabolites from tyelonol -> dies of liver failure
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Apoptosis
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Programmed cell death -> DOES NOT spills contents of interstitum into extracellular space (cell membrane is not disrupted thus no pain)
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2 mechanisms
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Extrinsinc(receptor mediated) and intrinsic(mitochondrial) -> activates caspases
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What is the function of caspases?
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A cysteine protease that causes activation of DNAses which degrade nuclear DNA -> leads to apoptosis
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What is the diagnostic tool to check for apoptosis?
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Use DNA ladder on gel electrophoresis
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What is the most important extrinsic factor apoptosis?
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1. TNF receptor 1 - initiated via cell surface receptors, 2. Fas (aka CD95)
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What molecule inhibits the extrinsic apoptosis pathway?
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FLIP - some viruses produce FLIP thus protecting the cell it just invaded from apoptosis
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Intrinsic apoptosis
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Elevation of Ca2+ b/c of ↑ mitochondrial permeability -> Cytochome C ->caspases -> starts apoptosis
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What are the anti-apoptosis molecules
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Bcl-2 and Bcl-x (seen in cancer cells b/c its immortal)
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What are the pro-apoptosic molecues
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Bak, bax, bim
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Which caspases are the initiators?
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Caspases 8 + 9
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Which caspases are the executioner?
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Caspases 3 + 6
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Lipid peroxidation
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Digestion of cell mediated by oxygen free radicals
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What is p53
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Tumor- suppressor gene - in the cell cycle (DNA level)
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In what phase of cell cycle is stopped b/c of p53?
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Cells arrest in G1 phase
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Digest cell from outside
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Heterophagy - digests bacteria, apoptotic cells, etc utilizing lysosomes to break stuff down
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Cell kills itself by itself
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Autophagy - digest itself utilizing lysosomes to break stuff down
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Where are lysosomes synthesized? Stored?
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Synthesized = rER, Stored = Golgi apparatus
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What type of drug are u developing a tolerance to if u have a hypertrophy of the smooth ER?
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Barbiturates
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What drug causes a lysosomal disease?
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Chloroquine
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What is the MOA of a RA drug on lysosomes?
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If the RA drug ↑ lysosomal pH it will inhibit the enzymes thus decreasing the autoimmune response
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What happens to the number of mitochondria in cell hypertrophy? Atrophy?
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Hypertrophy = ↑ number of mitochondria; atrophy = ↓ number of mitochondria
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Neurofibrillary tangles
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Alzheimers disease
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Altered linking lymphocyte antigen receptors to cytoskeleton
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Wiskott-aldrich syndrome
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Where is cholesterol ↑ and deposited?
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Atherosclerosis(injury of endothelium -> deposits cholesterol to make it hard) + xanthomas(deposits small tumors with high cholesterol in them)
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What type of changes are u looking for around an atherosclerotic blood vessel?
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Hyaline changes
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Anthracosis
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Blackened lung tissue from carbon/coal dust (exogenous generation of pigments)
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Lipofuscin
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Endogenous - generation of pigements due to lipid peroxidation b/c of oxygen free radicals (aging pigment)
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What color does melanin produce?
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Black-brown pigment formed when enzyme tyrosinase forms dihydroxyphenylalanine in melanocytes + homogentistic acid
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Hemocyderine
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Gold and yellow discoloration, compoenent of hemoglobin which contains Fe
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ochronosis
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Ochronosis is the syndrome caused by the accumulation of homogentisic acid in connective tissues
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Hemocyderine
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Accumulation of iron that is phacytosed by macrophages - ie a bruise
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Bilirubin
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Normal pigement in bile -> contains no Fe
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Metastatic calcification vs dystrophic calcification
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Metastatic calcification = calcification systemicly; dystrophic calcification = calcification at the site
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What is the disease of excessive cellular aging?
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Progeria - due to progressive decline in proliferative capacity and life span of cells
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What is cellular senescence
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Basically the cell has a finite number of times it can divide then it is stuck in a non-dividing state -> caused by shortening of telomeres after each cellular division
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What gene influence the aging process?
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IGF-1 pathway -> ↓ signaling = prolonged lifespan
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What is the cause of werner syndrome?
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Premature aging due to mutated helicase (DNA repair enzyme)
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In what situations does apoptosis occur in pathological events?
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1. Induced by injury, 2. viral infection(hepatitis), 3. cell death in tumors
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What is the morphology of apoptotic cell?
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1. Chromatin condensation (most common characteristic-very vivid in staining), 2. cell shrinkage
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What is the cell morphology of an apoptotic cell?
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1. Cell shrinkage, 2. chromatin condensation
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