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245 Cards in this Set
- Front
- Back
Antithrombogenic substances
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Prostacyclin (PGI2), nitric oxide, tissue plasminogen activator, thrombomodulin
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Steps in hemostasis
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1. Endothelial injury relases tissue factor (activates factor VII, extrinsic pathway); exposure of thrombogenic subendothelial collagen activates factor XII (intrinsic pathway), release of vWF; decreased synthesis of antithrombogenic substances; 2. Platelet adhesion to vWF through glycoprotein Ib; 3. Platelet activation with degranulation and synhesis of TXA2 and ADP (aggregators); 4. Aggregation mediated by TXA2 and ADP and fibrinogen/Gp IIb-IIIa
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Bernard Soulier syndrome
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Autosomal recessive. Deficiency of platelet GPIb. Defective platelet adhesion
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Glanzman thrombastenia
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Deficiency of Gp IIB-IIIa; defective platelet aggregation
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Immune thrombocytopenic pupura
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Antiplatelet antibodies and destruction in spleen by macrophages (bind IgG coated platelets via Fc receptor). Thrombocytopenia, prolonged bleeding time, normal PT and PTT. Petechiae, ecchymoses, menorrhagia, nosebleeds. Present in Wiskot-Aldrich
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Thrombotic thrombocytopenic purpura
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Platelet thrombi with scant fibrin with no activation of coagulation system. Fever, thrombocytopenia, hemolytic anemia, neurologic symptoms, renal failure. Increased bleeding time, normal PT/PTT, schistocytes
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Hemolytic uremic syndrome
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Gastroenteritis with bloody diarrhea, fever, thrombocytopenia, renal failure, hemolytic anemia. Produced by verotixin-producing E. coli 0157
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Activation of coagulation system
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Intrinsic pathway (Factor XII): exposure to subendothelial collagen; Extrinsic pathway (factor VII): tissue thromboplastin by endothelium
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Kinin cascade
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Hageman factor converts prekallikrein into kallikrein. HMWK is converted to bradykinin by kallikrein
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Fibrinolytic system cascade
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Kallikrein activates plasminogen into plasmin which inhibits fibrin from coagulation cascade
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Vitamin K-dependant factors
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Factors II, VII, IX, X. Both intrinsic and extrinsic paths need vitamin k-dependant gamma carboxylation
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Prothrombin time (PT)
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Tests extrinsic and common paths. Factors V, VII, X, prothrombin and fibrinogen. Used to monitor warfarin therapy
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MOA of warfarin
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Blocks epoxide reductase (activates vitamin K). Takes 3-4 days for effect due to long half life of previously carboxylated factors which are still circulating
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Partial thromboplastin time (PTT)
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Tests intrinsic and common paths. Factors XII, XI, IX, VIII, X, V, prothrombin, fibrinogen. Used to monitor heparin
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DIC
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Thrombocytopenia, prolonged PT/PTT, decreased fibrinogen, elevated D-dimers
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Hemophilia
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Deficiency of factor VIII or IX. X-linked recessive (affects males). Bleeding at circumcision, hemarthrosis, easy bruising and hematomas. No petechiae or ecchymoses. Normal platelets and bleeding time, normal PT, prolonged PTT (intrinsic path coagulopathy)
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Increased PT and PTT
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Vitamin K deficiency, liver disease
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Von Willenbrand disease
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bleeding from mucuous membranes, prolonged bleeding time, normal PT/PTT, abnormal response to ristocetin
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Auto mechanics
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Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
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Firefighters
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Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
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Wood stoves and space heaters
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Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
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Pesticide industry
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Organophosphate poisoning (acetylcholinesterase inhibitors) and arsenic. Lacrimation, salivation, miosis, weakness. Rx.: atropine
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Meat packing industry
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Plyvinyl chloride (PVC). Hepatic angiosarcoma
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Coal workers
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Anthracosis. Pulmonary fibrosis and respiratory distress
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Insulation workers
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Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
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Demolition workers
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Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
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Construction workers
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Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
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Shipyard workers
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Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
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Dry cleaners
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Carbon tetrachloride (CCL4). Liver centrilobular necrosis
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Rubber/chemical workers
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Benzene. Aplastic anemia, leukemia
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Battery factory workers
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Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood lead levels
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Plumbers
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Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood le
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Pottery paint
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Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood le
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Combustion of polyurethane foam during fires
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Cyanide poisoning. Blocks cytochrome oxidase. Hypoxia. Rx.: nitrites (form methhemoglobin which binds cyanide before it reaches tissues), thiosulfate bind cyanide forming thiocyanate
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Dental amalgams
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Mercury poisoning. Intention tremors, dementia, delirium
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Insecticides
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Mercury poisoning. Intention tremors, dementia, delirium
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Hat-making industry
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Mercury poisoning. Intention tremors, dementia, delirium
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Cancers produced by cigarette smoke
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Lung, oral cavitiy, pharynx, larynx, esophagus, pancreas, kidney
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Cardiovascular disease due to cigarette smoke
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Atherosclerosis (major risk factor), CAD, AMI, Buerger disease
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Respiratory disease due to cigarette smoke
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Chronic bronchitis, emphysema, asthma
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Diseases associated with alcohol
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Thiamine deficiency (Wernicke-Korsakoff), macrocytic anemia (folate deficiency), Mallory-Wiess, Boerhaave's syndrome, cirrhosis, esophageal varices, acute pancreatitis, congestive cardiomyopathy, hyperlipidemia
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Down syndrome
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Trisomy 21 due to meiotic nondisjunction (95%) or robertsonian translocation (4%); Severe mental retardation, mongoloid features, brushfeld spots, simian crease, heart defects, duodenal atresia, Hirchsprung, ALL, Alzheimer's by age 40
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Edward syndrome
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Trisomy 18. Mental retardation, low set ears, micrognathia, heart defects, overlapping flexed fingers, rocker-bottom feet
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Patau syndrome
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Trisomy 13. Mental retardation, cleft lip or palate, cardiac defects, renal defects, microcephaly, polydactyly
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Cri du chat
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5p deletion. Cat-like cry, mental retardation, heart defects, microcephaly
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Klinefelter syndrome
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47XXY. Male hypogonadism, testicular atrophy, infertility, female distribution of hair, gynecomastia, elevated LH/FSH, low levels of testosterone
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Turner syndrome
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45X0. Female hypogonadism, no barr body, no secondary sex characteristics, short stature, widely spaced niples, gonadal dysgenesis, amenorrhea, infertility, hypothyroidism, preductal coarctation of the aorta, bicuspid aortic valve
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Female hermaphrodite
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46XX. Female internal organs, virilized external genitalia. Cause: congenital adrenal hyperplasia, androgen-producing tumor
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Male hermaphrodite
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46XY. Testes present, female genitalia, testicular feminization. Cause: androgen insensitivity syndrome
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CCystic Phibrosis
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Chloride Channel protein defect, deletion of phe 508 on chromosome 7. Recurrent psudomona/staph infections, chronic bronchitis, bronchiectasis, atrophy of pancreatic ducts, pancreatic insuficiency, fat malabsorbtion, steatorrhea, infertility, meconium ileum, elevated NaCl sweat test
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PKU
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Deficiency of phenylalanine hydroxylase. Mental retardation by 6 months, light-colored hair and skin, musty odor. Avoid aspartame, monitor pregnancy
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Alkaptonuria
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"Black Homo" homogentisic acid oxidase deficiency. Black urine, black cartilage
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Albinism
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Tyrosinase deficiency. Increased risk of squamous carcinoma, no melanin
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Von Gierke disease
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Glucose 6 phosphatase deficiency. Hepatomegaly, fasting hypoglycemia, hyperuricemia
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Pompe disease
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Lysosomal alpha 1-4 glucosidase deficiency. Hepatomegaly, muscle hypotonia, cardiomegaly
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McArdle disease
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Myophosphorylase deficiency. Excersice-induced muscle cramps
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Tay SaX
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Hexosaminidase A deficiency with acumulation of glangliocerebroside GM2. Mutation of HEXA gene on chromoseme 15. Cherry-red spot on retina
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Nieman PickS
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Sphingomyelinase deficiency. Cherry-red spot on retina, hepatosplenomegaly, zebra bodie on EM
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Gaucher disease
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Glucocerebrosidase deficiency. In adulthood, hepatosplnomegaly, hypersplnism, lymphadenopathy
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Mucopolysaccharidosis
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Glycosaminoglycans acumulation. Mental retardation, cloudy cornea, coarse facial features, hepatosplnomegaly, skeletal deformities
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Familial hypercholesterolemia
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Mutation on LDL receptor gene on chromosome 19. Xanthomas, xanthelasmas, atherosclerosis, achiles tendon xanthoma
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Marfan syndrome
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Mutation of fibrillin gene on 15q. Tall, thin with big extremities, hyperextensible joints, pectus excavatum, ectopia lentis, disecting aortic aneurysm, aortic insuficiency, mitral prolapse
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Ehlers-Danlos
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Hyperxtensible skin and joints. Collagen gene defects
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Menkes disease
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Mutation in Cu+ efflux protein gene. High concentration of Cu+ that cant be released. Associated with Ehlers-Danlos type 9
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Neurofibromatosis type 1
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Von Recklinghousen disease (has 17 letters). NF-1 tumor suppressor gene mutation on chromosome 17. Normal gene product neurofibromim inhibits p21 ras oncoprotein. Neurofibromas, café-au-lait spots, Lisch nodules (pigmented iris hamartomas)
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Neurofibromatosis type 2
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NF-2 tumor suppressor gene mutation on chromosome 22. Bilateral acoustic neuromas, café-au-lait spots, pheochromocytoma
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Von Hippel Lindau disease
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Mutation on VPL tumor suppressor gene on chromosome 3p. Retinal hemangioblastoma, hemangioblastoma of cerebellum, brainstem and spinal cord, cysts of the liver, pancreas and kidneys, bilateral renal carcinomas
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Fragile X syndrome
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X-linked dominant mutations on FMR-1 gene. CGG triplet repeats. Retardation elongated face with large jaws, large everted ears, macroorchidism
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Huntington disease
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CAG triplet repeats of huntington gene produces neurotoxic protein. Progressive dementia, choreiform movements
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Prader-Willi syndrome
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Deletion of paternal 15q. Mental retardation, obesity, hypogonadism, hypotonia
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Angelman syndrome
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deletion of maternal 15q. Retardation, seizures, ataxia, inapropriate happy-puppet laughter
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Homocystinuria
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Cysthathione synthase deficiency. Resembles Marfan. Ectopic lens, arachnodactyly, eunuchoid proportions osteoporosis, atherosclerosis, DVT
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Classic 21B-Ohase deficiency
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Hypovolemia, hyponatremia, female pseudohermaphrodite, hirsutism (increased 17 KS), skin hyperpigmentation (high ACTH increases melanin). Labs: increased serum 17OH-progesterone, hyperkalemia, metabolic acidosis, increased 17KS, decreased 17OHCS, hypocortisolism
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Non-classic 21B-Ohase deficiency
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Increase in 17 KS, hirsutism, no salt loss, acne in females, secondary amenorrhea. Labs: increased 17OH pregenterone
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Classic 11OHase deficiency
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Salt retention/hypertension (11-deoxycorticosterone), increased 17KS (virilization), skin hyperpigmentation
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17OHase deficiency
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Salt retention, hypertension, (aldosterone), female hypogonadism (decreased 17KS), male pseudohermaphrodite (low 17KS). Labs: low 17KS, 17OHCS, hypocortisolism, increased ACTH
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Clinical features of SLE
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Type II and III hypersensitivity reactions. Pancytopenia, arthritis, butterfly rash, diffuse proliferative glomerulonephritis, Libman-Sacks endocarditis. ANA, anti-DNA, anti-Sm, anti-histone (drug-induced lupus). Rx.: steroids
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Sjogren syndrome
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Autoantibodies against lacrimal and salivary glands. Keratoconjunctivitis, corneal ulcers (dry eyes), xerostomia (dry mouth). Anti-Ro (SS-A), anti-La (SS-B). 15% of rheumatoid arthritis patients have Sjogren.
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Mikulicz syndrome
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Enlargement of the salivary and lacrimal glands associated with Sjogren syndrome
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Diffuse scleroderma
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Fibroblast stimulation and deposition of collagen in the skin and internal organs. Anti-DNA topoisomarease I (Scl-70) (helicase). Skin involvement, dysphagia, malabsorption, pulmonary fibrosis (dyspnea), cardiac fibrosis (arrhythmias), kidney fibrosis (renal failure)
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Localized scleroderma (CREST)
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Fibroblast stimulation and deposition of collagen. Anti-centromere antibodies. Calcinosis, Raynaud, esophageal dysmoility, sclerodactyly, telangiectasia.
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Bruton's agammaglobulinemia
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X-linked recessive. No B cells, No Igs. Recurrent staph, haemophilus and strep infections after 6 months. Increased pre-B cells. Mutation of B-cell Bruton tyrosine kinase (btK).
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Common variable immunodeficiency
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B-cell maturation defect. Hypogammaglubulinemia, recurrent bacterial infections, giardia lamblia.
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DiGeorge syndrome
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Failure to develop 3rd and 4th pharyngeal puches results in absence of parathyroid and thymus glands, hypocalcemia, tetany, T-cell deficiency, recurrent viral infections, heart defects, chronic candidiasis
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SCID
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B and T cell deficiency due to mutation of IL-2 receptor (x-linked), adenosine deaminase deficiency (AR) or failure to make MHC II. Recurrent infections and susceptibility to candida, CMV and p. carinii
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Wiskot-Aldrich syndrome
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X-linked recessive. "WIPE": recurrent infections, thrombocytopenic purpura, eczema, risk of lymphomas, low IgM
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Ataxia-Telangiectasia
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Ataxia, spider angiomas, low IgA, defect of DNA repair enzyme
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Chronic granulomatous disease
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Low NADPH oxidase. Recurrent catalase+ infections, negative nitroblue tetrazolium test.
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Leukocyte adhesion deficiency
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Defect of CD-18 (LFA-1 beta chain), no pus formation, failure of umbilical cord to detach
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Chediak-Higashi
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Defect in microtubules with no phagocytosis by lysosome. Partial albinism, peripheral neuropahty, recurrent infections
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Hereditary angioedema
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Edema at mucosal surfaces. Defect of C1-INH (esterase inhibitor). Decreased C1, C2, C4
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Hyper IgM
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Defect of CD-40L on T-lymphocytes. No isotope switching, increased IgM
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MHC-I deficiency
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Normal CD4, no CD8. Failure of TAP-1 to transport peptides to MHC-I groove
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Amyloid stains
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Stains red with Congo-red stain then apple green birefringence under polarized light
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Signs and symptoms of amyloidosis
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Nephrotic syndrome, renal failure, arrythmias, CHF, hepatosplenomegaly, macroglosia
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Mediators of leukocyte margination
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Selectins mediate margination. P and E selctins on endothelium bind Sialyl-Lewis on leukocyte; GlyCAM/CD34 on endothelium binds L-selectin on leukocyte
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Mediators of leukocyte adhesion
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Integrins mediate adhesion. ICAM, VCAM on endothelium bind LFA-1 and VLA on leukocyte
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Regulators of leukocyte margination and adhesion
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Histamine upregulates P-selectin. IL-1 and TNF induce E-selectin, ICAM and VCAM. Chemotactic agents cause conformational change of LFA-1
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Leukocyte adhesion deficiency
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Defect of CD18 (beta chain subunit of LFA-1 integrin on leukocytes). Recurrent infections, no pus formation, failure of umbilical cord to detach
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Chemotactic factors
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N-formyl methionine, leukotriene B4, C5a, IL-8
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Opsonins
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Fc portion of IgG, c3b, C reactive protein
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Chediak-Higashi syndrome
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Defect of microtubule polymerization causes defect in chemotaxis and degranulation. Partial albinism, peripheral neuropathy
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CGD
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NADPH oxidase deficiency. No production of superoxide for respiratory burst. Recurrent catalase+ infections, negative nitroblue tetrazolium test
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Arachidonic acid products
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AA producedd by phospholipase A2 (inhibited by steroids). Produces leukotrienes, prostaglandins and thromboxane A2
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Lypoxigenase pathway
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Arachidonic acid is converted to leukotrienes by 5-lypoxigenase. LTB4 --> chemotaxis. LTC4, D4, E4 --> bronchoconstriction
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Cycloxigenase pathway
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Arachidonic acid is converted to TXA2 and prostaglandins (NSAIDs block). TXA2 --> vasoconstriction, platelet aggregator. PGI2, PGE2, PGF2
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Mediators of vasodilation
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Histamine , bradikinin, PGI2, PGD2, E2, F2
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Mediators of pain
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Bradikinin, PGE2
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Mediators of increased permeability
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Histamine, Bradikinin
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Mediators of vasoconstriction
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TXA2, LTC4, D4, E4
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Mediators of bronchoconstriction
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LTC4, D4, E4, bradikinin
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Mediators of fever
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IL-1, PGD2, E2, F2
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Anaphilotoxins
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C3a, C5a. Directly stimulate histamine release from basophils, mast cells and platelets
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C3b
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Opsonin; neutrophils, macrophages and monocytes have C3b receptros
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Bradikinin synthesis and actions
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Synthesized from activation of prekalikrein by factor XII (Hageman). Kalikrein cleaves HMWK into bradikinin. Vasodilator, increased permeability, brnchoconstrictor, pain
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PGE2
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Vasodilation in kidneys, increases renal blood flow, increases gastric mucosal blood flow (mucoprotection), activates osteoclasts, fever, pain, maintains ductus arteriosus
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Prostacyclin (PGI2)
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Vasodilation and inhibits platelet aggregation
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IL-1
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Stimulates PGE2 synthesis in hypothalamus --> fever; B-cell stimulation to synthesize Ig; osteoclast activation (released by osteoblasts under PTH stimulation); lytic bone lessions of multiple myeloma; increases adhesion molecules in endothelium; increases acute phase reactants
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Hageman factor
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Activates intrinsic coagulation system, kinin cascade and fibrinolytic system
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PGF
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Uterine muscle contraction (cause pf primary amenorrhea)
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gamma interferon
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Produced by CD4 cells and NK cells. Activates macrophages; antiviral properties; class I and class II antigens; increases IL-2, IL-12 production by CD4 cells
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IL-2
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Produced by CD4 cells. T cell growth factor. Promotes B cell and NK cell proliferation
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IL-6
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Synthesis of acute phase reactants
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Factors that increase adhesion molecule synthesis
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C5a, LTB4, IL-1, TNF
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Key cells in acute and chronic inflamation
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Acute: neutrophil has IgG and C3b receptros; Chronic: macrophage has receptors for IgG and C3b, process antigen and secrete IL-1, IL-12 and TNF
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Chronic granulomatous inflamation
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Epitheloid cells and multinucleated giant cells surrounded by a rim of lymphocytes with central caseous necrosis
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Type I collagen
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skin, bones, tendons and most organs
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Type II collagen
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Cartilage and vitreous humor
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Type III collagen
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granulation tissue
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Type IV collagen
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basement membranes
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Composition of basement membranes
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Has negative charge. Collagen type IV, proteoglycans (heparan sulfate), laminin, fibronectin
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Nitrosamines
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Gastric CA, Esophagus
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Cigarette smoke
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Larynx, ling, renal cell carcinoma, transitional cell carcinoma
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Polycyclic aromatic hydrocarbons
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Bronchogenic CA
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Asbestos
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Bronchogenic CA, mesothelioma
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Chromium and nickel
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Bronchogenic CA
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Arsenic
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Squamous cell CA of skin and lung, angiosarcoma of liver
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Vinyl chloride (PVC)
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Liver angiosarcoma
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Alkalating agents
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Leukemia, lymphoma
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Benzene
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Leukemia, lymphoma
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Napthalene
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Bladder CA
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CCL4
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Liver centrilobular necrosis
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HTLV-1
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Adult T-cell leukemia
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HBV, HCV
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Hepatocellular CA
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EBV
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Burkitt's lymphoma, nasopharyngeal CA
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HPV
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Cervical CA (16, 18)
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HHV-8
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Kaposi sarcoma
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hst-1 & int-2
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Cancer of stomach, breast, bladder and melanoma; produces growth factors; overexpression
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sis
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Astrocytoma; produces PDGF; overexpression
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erb-B1
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SCC of lung; produces EGF receptor; overexpression
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erb-B2
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Breast, ovary and lung CA; produces EGF receptor; amplification
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erb-B3
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Breast; produces EGF receptor; overexpression
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ret
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MEN II & III, medullary thyroid CA; produces glial neurotrophic factor receptor; Point mutation
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abl
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CML, ALL; produces signal transduction proteins; translocation t(9:22), Philadelhpia chromosome
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Ki-ras
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Lung, pancreas and colon; produces GTP binding proteins; Point mutation
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c-myc
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Burkitt lymphoma; produces nuclear regulatory protein; translocation t(8:14). When associated to p53 apoptosis; when associated to bcl-2 inhibits apoptosis
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L-myc
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Small cell lung CA; produces nuclear regulatory protein; amplification
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N-myc
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Neuroblastoma; produces nuclear regulatory protein; amplification
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bcl-1
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Mantle cell lymphoma; produces cyclin D protein; translocation t(11:14)
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CDK4
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Melanoma; produces cdk; amplification
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bcl-2
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Normally prevents apoptosis. Follicular and undiferentiated lymphomas t(14:18). Chromosome 14: Ig heavy chain; chromosome 18 bcl-2
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c-kit
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gastrointestinal stromal tumor
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p53
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Normally prevents a cell with damaged DNA from entering S-phase by inhibiting cyclin/cdk. Colon, breast, CNS, lung. On chromosome 17
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Rb
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Normally prevents a cell from entering S phase. Retinoblastoma, osteogenic sarcoma. Inactivated product by cyclin/cdk. On chromosome 13
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Alpha fetoprotein
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Hepatocellular CA, testicular tumors
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B-hCG
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Trophoblastic tumors, chroriocarcinoma
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Calcitonin
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Medullary CA of thyroid
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CEA
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lung, pancreas, stomach, breast, colon
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CA-125
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Ovarian CA
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CA19-9
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Pancreatic CA
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Placental alkaline phosphatase
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Seminoma
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Prostatic acid phosphatase
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Prostate CA
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PSA
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Prostate CA
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Alkaline phosphatase
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Metastasis to bone, primary billiary cirrhosis
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VHL
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Chr 3p. Von Hippel Lindau, renal cell CA
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WT-1, WT-2
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11p. Wilm tumor
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BRCA-1
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17q. Hereditary breast and ovarian CA
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BRCA-2
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13q. Hereditary breast CA
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APC
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5q. Adenomatous polyps and colon CA
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DCC
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18q. Colon CA
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NF-1
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17q. Neurofibromatosis
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NF-2
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22q. Acoustic neuromas and meningiomas
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Down Syndrome
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ALL, AML
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Xeroderma pigmentosum, albinism
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Squamous cell, basal cell CA, melanoma
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Chronic atrophic gastritis, pernicious anemia, H. pylory
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Gastric adenocarcinoma
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Tuberous sclerosis
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Astrocytoma; produces PDGF; overexpression
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Actinic keratosis
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Squamous cell CA of skin and lung, angiosarcoma of liver
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Barret's esophagus
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Esophageal adenocarcinoma
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Plummer-Vinson syndrome
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Iron deficiency causes atrophic glositis, esophageal webs, anemia, squamous cell CA of esophagus
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Cirrhosis
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Hepatocellular CA
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Ulcerative colitis
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Colonic adenocarcinoma
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Paget's
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Osteosarcoma
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Immunodeficiency
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Malignant lymphomas
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AIDS
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Non-Hodgikin's, Kaposi
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Dysplastic nevus
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Malignant melanoma
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Radiation
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Sarcoma
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Small cell lung CA paraneoplastic syndromes
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Cushing's (ACTH), SIADH (ADH)
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Squamous cell lung CA paraneoplastic syndrome
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Hypercalcemia (PTH), TGF-b, TNF, IL-1
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Renal cell CA paraneoplastic syndrome
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Polycythemia (EPO), hypertension (renin)
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Thymoma, Small cell lung CA paraneoplastic syndromes
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Lamber-Eaton (antibodies against presynaptic CA channels at neuromuscular junction)
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Leukemias and lymphomas paraneoplastic syndromes
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Gout (hyperuricemia due to excess nucelic acid turnover)
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Acanthosis nicrans
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Gastric adenocarcinoma
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Carcinoid tumor or medullary thyroid CA paraneoplastic syndromes
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Flushing, diarrhea (serotonin)
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alpha1-antitrypsin
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Hepatocellular CA
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Bence Jones protein
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Multiple Myeloma (Ig light chains in urine)
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MEN-I
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Pituitary (ACTH, Cushings), parathyroid (hypercalcemia), pancreas (zollinger-ellison, insulinoma)
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MEN-II
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medullary thyroid CA, parathyroid adenoma (hypercalcemia), pheocromocytoma (hypertension)
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5 leading causes of death in US
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1. Heart disease; 2. Cancer; 3. Cerebrovascular disease; 4. COPD; 5. Accidents
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3 leading causes of death in children in US
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1. Accidents; 2. Cancer; 3. Congenital abnormalities
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3 most common cancers in males
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1. Prostate; 2. Lung and bronchus; 3. Colon/rectum
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3 most common cancers in females
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1. Breast; 2. Lung; 3. Colon/rectum
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Top 3 cancer mortality in males
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1. Lung; 2. Prostate; 3. Colon/rectum
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Top 3 cancer mortality in females
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1. Lung; 2. Breast; 3. Colon/rectum
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5 causes of tissue hypoxia
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ischemia, hypoxemia, ETC block, uncoupled ETC, AV shunts
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Ultimate effects of tissue hypoxia
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No O2 to accept electrons in ETC, no production of ATP. Na/K pump fails and cell swells (reversible change). Ribosomes fall from RER. Disruption of cell membrane and mitochondria induces apoptosis.
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Effects of low ATP in cell
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Increased glycolysis to support ATPase pump. Anaerobic glycolysis produces lactate with decreased intracellular pH which denatures proteins (coagulation necrosis), cell swelling, entry of calcium and apoptosis
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Pathophysiology of cell injury in hypoxia
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ETC fails due to lack of oxygen; 2. No ATP production in ETC increases anaerobic glycolysis (high citrate and AMP activate PFK-1); 3. increased lactate decreases cell pH which denatures proteins and produces coagulation necrosis; 4. ATPase fails and cell swells with fall off of ribosomes from RER; 5. disruption of cell membrane with entry of Ca activates phospholipase (lipid peroxidation), complement activation, nuclear enzymes with pyknosis and destruction of mitochondria and apoptosis
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What is methhemoglobin?
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Hemoglobin with oxidized (Fe3+) iron that cant bind O2. Decreases SaO2 and produces cyanosis. Caused by nitro/sulfa compounds. Rx.: methylene blue
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Increased PACO2, decreased PaO2, decreased O2 content, decreased SaO2
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Respiratory acidosis
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Normal PaO2 and SaO2, decreased Hb
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Anemia
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Normal Hb, PaO2, decreased SaO2, decreased O2 content
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CO poisoning or methhemoglobinemia
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CO poisoning tissue hypoxia
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Decreased O2 content and SaO2, normal PaO2, left shift of dissociation curve and cytochrome oxidase inhibition all cause hypoxia. Produced by car exhaust, heaters, smoke inhalation, wood stoves. Rx.: 100% O2. First symptom: headache
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Factors that left-shift O2 dissociation curve and decrease P50
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Decreased 2,3BPG, CO, MetHb, HbF, hypothermia, alkalosis
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Factors that right-shift O2 dissociation curve and increase P50
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Increased 2,3BPG, fever, acidosis
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Causes of hypoxia with normal O2 content
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Ischemia, cyanide poisoning, ETC uncouplers (alcohol, salicylates, dinitrophenol)
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Free radical metabolism
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NADPH oxidase and spontaneous superoxide, Superoxide dismutase makes H2O2 from superoxide. Catalase breaks down H2O2. Gluthathione reductase and GSH peroxide breakdwon H2)2 using reduced GSH and NADPH from G6PDH in HMP shunt
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Causes of free radical injury
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Aging process produces lipofuscin which peroxidates membrane; MPO system, O2 free radicals, ionizing radiation, acetaminophen (treat with acetylcyteine), CCl4 poisoning
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Features of apoptosis
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Eosinophilic cytoplasm; pyknotic nucleus, no inflamatory infiltrate
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Physiologic examples of apoptosis
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Thymus involution, Mullerian and Wolffian structure involution, gravid uterus
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Pathologic examples of apoptosis
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Councilman bodies in viral hepatitis, psammoma bodies, cancer
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Coagulation necrosis
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Denaturing and coagulation of proteins in cytoplasm (infarction). Pale Vs. hemorrhagic infarcts
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Liquefactive necrosis
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Neutrophil destruction with hemolytic enzymes. Abesesses, wet gangrene, brain, pancreas
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Caseous necrosis
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Combination of coagulation and liquefaction necrosis. Cheese-like material, casseating granulomas with macrophages
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Fat necrosis
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Lipases on fatty tissue. Pancreas. Chalky-white appearance
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Fibrinoid necrosis
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Histologically resembles fibrin. Eosinophilic mitral valve vegetations, immunocomplexes
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Fatty liver change
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In alcoholics - liver stores excess tryglycerides because increased NADH produces glycerol 3P and increased acetate (acetyl CoA) increases FA synthesis. In kwashiorkor, no apolipoproteins for VLDL
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Regulation of apoptosis
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Genes bcl-2 (inhibits apoptosis) prevents release of cytochrome C and binds protease activating factor (Apaf-1); p53 stimulates apoptosis. Mediated by caspases. Stimulated by cell injury, lack of hormones, Fas and TNF
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Rb suppressor gene and Rb protein
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Located on chromosome 13. Produces unphosphorylated Rb protein which stops cell from entering S phase. Phosphorylation by cyclin D/cdk complex allows it to enter S phase. Mutation of Rb gene produces cancer
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cdk/cyclin D complex
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When activated it phosphorylates Rb protein allowing cell to enter S phase
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p53 suppressor gene
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Located on chromosome 17. Produces a protein that inactivates cyclin D/cdk complex preventing Rb protein phosphorylation which keeps cell in G1
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Fibronectin
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Binds collagen, fibrin and integrins; adhesion glycoprotein of extracellular matrix; chemotactic for fibroblasts and endothelial cells
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VEGF
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vascular endothelial growth factor; important in angiogenesis
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FGF
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Fibroblast growth factor; important in angiogenesis
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PDGF
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Stimulates granulation tissue formation; stimulates proliferation of smooth muscle, fibroblasts and endothelium
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Laminin
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Adhesion protein in basement membranes; binds type IV collagen, integrins and ECM components
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