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89 Cards in this Set
- Front
- Back
How do cells ADAPT to environmental stress?
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hypertrophy, hyperplasia, aplasia, hypoplasia, atrophy, metaplasia, dysplasia
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What is hypertrophy?
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Increase in organ/tissue size due to increase in SIZE OF CELLS, w/increased expression of genes and protein synth
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What causes hypertrophy?
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Adaption to...increased workload (hypertension), increased endocrine stim (puberty, preg)
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What is hyperplasia
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Increase in size of organ/tissue due to increase in NUMBER OF CELLS, w/inc express of growth-promoting genes (proto-oncogenes), inc DNA synth, cell div; may occur with hypertrophy
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Physiologic causes of hyperplasia?
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-compensatory (after partial hepatectomy)-hormonal stim (breast devel)-antigenic stim (lymphoid hyperplasia)
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Pathologic causes of hyperplasia?
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-endometrial hyperplasia-prostatic hyperplasia of aging
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What is aplasia?
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Failure of cell production
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Examples of aplasia?
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-fetal development, can result in AGENESIS (absence of organ)-late in life, permanent loss of precursor cells in proliferative tissues (e.g. marrow)
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What is hypoplasia?
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Decrease in cell production, less extreme than aplasia
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When is hypoplasia seen?
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partial lack of growth and maturation of gonadal structures in TURNER SYNDROME and KLINEFELTER SYNDROME
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What is atrophy?
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Decrease in size and functional ability of organ/tissue due to dec. in mass of pre-existing cells
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Markers of atrophy?
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Lipofuscin granules, autophagosomes on EM, intracytoplasmic vacuoles w/debris
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What causes atrophy?
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Disuse, ischemia, malnut, lack of endocrine stim, aging, denervation
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3 types of metaplasia?
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Squamous, osseous, and myeloid metaplasia
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What is metaplasia?
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Replacement of one differentiated tissue by another (usu. reversible)
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What is squamous metaplasia?
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When epithelial cells are replaced by squamous epith, often reversible
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Where does squamous metaplasia occur?
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-Replacement of columnar epith at squmocolumnar jn of cervix by squamous epith-In resp epith of bronchus, endometrium, and panc ducts
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What causes squamous metaplasia?
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Chronic irritation (e.g. smoking), vit A deficiency
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What is osseus metaplasia?
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formation of new bone at sites of tissue injury (cartilaginous metaplasia may also occur)
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What is myeloid metaplasia?aka. extramedullary hematopoiesis
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Prolif. of hematopoietic tissue in non-bone marrow sites (e.g. liver or spleen)
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What is dysplasia?
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Abnormal prolif of cells, characterized by changes in cell size, shape, loss of cellular organiz; premalignantex: cervical dysplasia
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What causes dysplasia?
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similar stimuli to those that produce cancer (HPV, esophageal reflux)
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Causes of hypoxic cell injury?
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Ischemia (most common), anemia, CO poisoning, decreased tissue perfusion (hypotens), dec oxygenation of blood (pulm disease)
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What happens during EARLY hypoxic cell injury? 3
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1.AFFECTS MITOCHONDRIA -> dec oxidative phosphorylation and ATP synth, and failure of memb pump2. disaggregation of ribosomes and dec prot synth3. Stim of phosphofructokinase
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What happens when Na-K ATPase fails?
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1. cellular SWELLING, aka hydropic change (large vacuoles in cytoplasm)2. swelling of ER 3. swelling of mitochon (Ca, H2O, Na influx, K efflux)
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What happens when phosphofructokinase activity increase?
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inc glycolysis, lactate accum, dec intracell pH (which causes reversible clumping of nuclear chromatin)
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What is a pathophysiological correlate of decreased protein synthesis?
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Lipid deposition (fatty change) --> apoproteins required for lipid mobilization
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What are the signs of reversible membrane damage?
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Myelin figures (whorl-like structures), cell blebs (cell surf deformity due to disrupted cytoskel)
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What happens during LATE hypoxic cell injury?
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MEMBRANE DAMAGE -> Ca influx into mitochondria, leakage of lysosomal enzymes
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When does the cell reach the POINT OF NO RETURN?
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massive Ca influx, irrevers damage to memb and oxidat phosphor, calcification of mitochon, intracellular activation of lysosomal hydrolases
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What are the cellular markers of the point of no return? (indicates necrosis)
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Myocardial enzymes in serum: AST (aspartate aminotransferase), LDH (lactate dehydrogenase), CK (creatine kinase), troponins, myoglobinLiver enzymes in serum: ALT (alanine aminotransferase), AST, alkaline phosphatase, GGT (gamma-glutamyltransferase)
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How long does it take for hypoxic injury to become irreversible?
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3-5mins for neurons1-2hrs of myocardium and hepatocytesmany hours for skel muscle
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How are free radicals generated?
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-Normal metabolism-oxygen toxicity (alveolar damage/ARDS, retrolental fibroplasia)-ionizing radiation-UV light-drugs and chemicals (promote prolif of SER and P-450 system)-reperfusion after ischemic injury
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What are our protective factors against free radicals?
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1. Intracellular enzymes (glutathione peroxidase, catalase, superoxide dismutase)2. Exogenous and enogenous antioxidants (vit A, C, E, cysteine, etc)3. Spontaneous decay
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What is a good example of chemical injury to the liver?
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CCl4 -> *CCl3 by P-450 system in the SER*CCl3 causes free radical injury:1. disaggreg of ribosomes, dec protein synth, results in FATTY CHANGE2. Memb damage, cell swelling, Ca influx, mitoch damage, protein denat, cell death
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What is necrosis?
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Sum of degradative and inflammatory reactions occuring AFTER TISSUE DEATH IS CAUSED BY INJURY; must be in a living organism though
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What is autolysis?
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degradative rxn in cells, caused by intracell enzymes indigenous to the cell**postmortem autolysis occurs after organismal death but IS NOT NECROTIC**
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What is heterolysis?
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cellular degradation by enzymes derived from sources extrinsic to the cell
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What is coagulative necrosis?
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most common, results from sudden cutoff of blood supply, causes protein denaturation, usu occurs in heart, kidney
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Characteristic pathologic changes seen in coagulative necrosis?
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preservation of tissue architecture in early stages, increased eosinophilia, nuclear changes
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What is the morphologic hallmark of irreversible cell injury and necrosis?
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NUCLEAR CHANGES: pyknosis, karyorrhexis, karyolysis, disappearance of stainable nuclei
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What is pyknosis?
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chromatin clumping and shrinking with inc basophilia
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What is karyorrhexis?
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fragmentation of chromatin
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What is karyolysis?
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fading of chromatin material
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What is liquefactive necrosis?
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enzymatic liquefaction of necrotic tissues that results from interruption of blood supply (via autolytic mechs), usu in CNS, caused by ischemia (abscesses, brain infarcts, etc); also occurs in areas of bacterial infection (suppurative infections) via heterolytic mechs
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Where does liquefactive necrosis usually occur?
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usu in CNS (via autolytic mechs); also occurs in areas of bacterial infection (suppurative infections) via heterolytic mechs
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Characteristic pathologic changes seen in liquefactive necrosis?
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necrotic tissue soft and liquefied
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What is caseous necrosis?
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combination of coagulative and liquefactive necrosis; occurs as part of granulomatous inflammation, and is a manifestation of partial immunity caused by immune cells
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Characteristic pathologic changes seen in caseous necrosis?
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architecture not preserved, but tissue not liquefied, gross: cheese-like consistencyhistologic: amorphous eosinophilic appearance
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In what disease is caseous necrosis most commonly seen?
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TB
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What are the common sites of gangrenous necrosis?
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usu. seen w/interruption of blood supply to: lower limbs, GI tract, gallbladder, testes
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What is wet gangrene?
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when complicated by infective heterolysis and consequent liquefactive necr
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What is dry gangrene?
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when characterized by coagulative necr w/o liquefaction
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What is fibrinoid necrosis?
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assoc w/immune-mediated vascular damage, characterized by deposition of fibrin-like proteinaceous material in arterial walls
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Characteristic pathologic changes of fibrinoid necrosis?
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smudgy pink appearance in vascular walls, eosinophilc homogeneous appearance
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What is fat necrosis?
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caused by the action of lipases on fatty tissue (e.g. w/pancreatic damage)
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What is traumatic fat necrosis?
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occurs after severe injury to tissue w/high fat content (eg breast)
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What is enzymatic fat necrosis?
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complication of acute hemorrhagic pancreatitis -> panc enzymes diffuse into tissue and digest parenchyma, liberated fatty acids form calcium salts (saponification), vessels are eroded, hemorrhage
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Characteristic pathologic changes of fat necrosis?
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necrotic fat cells, acute inflam, hemorrhage, calcium soap formation, clustering of lipid-laden macrophages (in panc)
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What is apoptosis?
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programmed cell death; active process under genetic control, mediated by cascade of capases (digest nuclear cytoskeleton proteins and activate endonucleases); impt mech for removal of cells; involves single cells or small clusters
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Morphologic changes associated with apoptosis?
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cytoplasmic and cell shrinking, increased eosinophilic staining, nuclear chromatin condenses and fragments, blebbing, cell fragments are phagocytosed, NO INFLAMMATORY REACTION
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Stimuli for apoptosis?
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-cell injury and DNA damage-lack of horm/cytoki/growth factors-receptor-ligand signals (Fas binding to Fas ligand, TNF binding to TNFR1)
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Biochemical changes in apoptosis?
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cytochrome-c and bcl-2 activate capases (digest nuclear cytoskeleton proteins and activate endonucleases); REGULAR DNA fragmentation at nucleosomal boundaries ("laddered" gel pattern)
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What genes regulate apoptosis?
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bcl-2 inhibitsbax stimulatesp53 stimulates by decreasing transcription of bcl-2 and increasing transcrip of bax
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Physiologic examples of apoptosis?
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embryogenesis, hormone-dependent apop (menstruation), selective death of lymphocytes in thymus
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Pathologic examples of apoptosis?
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viral hep (Councilman body), graft vs host disease, CF (duct obstruction and panc atrophy)
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Possible causes of fatty change (steatosis)?
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1. inc transport of triglyc or fatty acids to cells2. dec mobilization of fat from cells (usu. due to dec apoproteins required for transport -> **thus fatty change is linked to disagg of ribo and dec prot synth**)3. dec use of fat by cells4. overproduction of fat in cellsusu in heart, liver, kidney
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What is hyaline change?
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protein accumulations in cells; appear homogeneous, glassy, eosinophilic
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Commonly accumulated exogenous pigments?
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carbon/silica/dust (pulmonary), plumbism (lead), argyria (silver)
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Commonly accumulated endogenous pigments?
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Melanin, bilirubin, hemosiderin, lipofuscin
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What are changes in melanin pigmentation indicative of?
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Increased pig: tanning, wide variety of disease conditionsDecreased pig: albinism, vitiligo
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Breakdown of what forms bilirubin?
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bilirubin is catabolic product of heme moiety of hemoglobin (and to small extent myoglobin)
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Types of jaundice?
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Hemolytic (destruc of RBCs)Hepatocellular (assoc w/parenchymal liver damage)Obstructive (assoc w/intra or extrahepatic obstruction of biliary tract)
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What is hemosiderin?
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iron-containing pigment, consists of golden-brown amorphous ferritin aggregates in tissues, stains blue w/Prussian blue dye
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What is local hemosiderosis?
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local deposition of hemosiderin (derived from breakdown of hemoglobin), usu results from hemorrhage
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What is systemic hemosiderosis?
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generalized hemosiderin deposition W/O tissue/organ damage; may result from hemorr, mult transfusions, hemolysis, excessive dietary iron, often w/EtOH consumption
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What is hemochromatosis?
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extensive accum of hemosiderin w/tissue damage, scarring, organ dysfn
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Characteristics of hereditary hemochromatosis?
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mutation in Hfe gene; causes TRIAD of micronodular cirrhosis, diabetes mellitus, skin pigmentation (= "bronze diabetes"); causes inc serum iron and dec total iron binding capac (TIBC)
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Common cause of secondary hemochromatosis?
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usu caused by mult blood transfusions administered to pts w/hereditary hemolytic anemias (eg beta thalassemia major)
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What is lipofuscin?
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yellowish, fat-soluble pigment, end product of memb lipid peroxidation, aka "wear and tear pigment"
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Where is lipofuscin most often seen?
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elderly pts, w/in hepatocyes and at poles of nuclei of myocardial cells
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What is "brown atrophy"?
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Combination of lipofuscin accum and atrophy of organs
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What is "bronze diabetes"?
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occus in hereditary hemochromatosis; caused by TRIAD of micronodular cirrhosis, diabetes mellitus, skin pigmentation
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Causes of metastatic calcification?
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hypercalcemia (usu resulting from hyperparathyroidism), osteolytic tumors, hypervitaminosis D, excess Ca intake
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Causes of dystrophic calcification?
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occurs in previously damaged tissues (eg old trauma, TB lesions, scarred valves, atherosclerotic lesions); NOT caused by hypercalcemia (normal serum Ca conc.)
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What is causal mechanism of abnormal protein folding?
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failure of structural stabilization or degradation by chaperones (e.g. ubiquitin, a heat shock protein)
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What are 2 major consequences of abnormal protein folding?
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abnormal protein aggregation, abnormal prot transport/secretion
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What diseases are characterized by abnormal protein aggregation?
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amyloidosis, Alzheimers, Huntingtons, Parkinsons, and perhaps prion diseases (eg mad cow)
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What diseases are characterized by abnormal protein transport and secretion?
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CF, alpha-1-antitrypsin deficiency
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