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85 Cards in this Set
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- Back
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What is apoptosis? What are the types?
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Programmed cell death; ATP is required.
1. intrinsic pathway--occurs in embryogenesis, hormone induction, atrophy, and after injurious stimuli. anti and pro apoptotic factors change to favor increased mito permeability and release of cytochrome c 2. extrinsic pathway--occurs c ligand-R interactions (eg Fas ligand binding to Fas or CTL releaasing perforin and granzyme B) Both lead to activation of caspases->charac by cell shrinkage, nuclear shrinkage, basophilia (pyknosis), membrane blebbing, pyknotic nuclear fragmentation (kayorrhexis), nuclear fading (karolysis), formation of apoptotic bodies, which are phagocytosed. ayn inflammation. |
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WHat are features of necrosis?
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=enzymatic degradation and protein denaturation of a cell resulting fr exogenous injury; intracell components exatravasate. inflammatory process
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What are the types of necrosis and in what tissues do these occur?
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1. coagulative: heart, liver, kidney
2. liquefactive: brain, bacterial abcess, pleural effusion 3. caseous: TB, fungi 4. fatty: pancreas (saponification) 5. fibrinoid: blood vessels 6. gangrenous: dry (ischemic coagulative) or wet (c bacteria); common in limbs and GI tract |
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What are cell mediators activated in intrinsic and extrinsic apoptosis?
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Intrinsic:
inc in Bax (pro apoptotic) dec in Bcl-2 (anti apoptotic) -> cyt c released from mito->activate cellular caspases Extrinsic: Fas-FasL, granzyme B, perforin --> activate cell caspases |
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What forms of cell injury are irreversible or reversible c Oxygen reperfusion?
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Reversible c Oxygen:
dec ATP synth, cell swelling (b/c if ayn ATP, Na/K pump can't work), nuclear chromatin clumping, dec glycogen, fatty change, ribosomal detachment (dec prot synth) Irreversible: nuclear pyknosis, karyolysis, kayorrhexis, Ca influx->activates caspases, plasma membrane dmg, lysosomal rupture, mito permeability |
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Where do red vs pale infarcts occur?
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Red (hemorrhagic infarcts) occur in loose tissues c collaterals: liver, lung, intestine, or following reperfusion--due to free radical injury
Pale infarcts occur in solid tissues c single blood supply, like heart, kidney, spleen |
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What is atrophy? What are causes?
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atrophy is reduction in size or number of cells
Causes: 1. dec hormones (uterus/vagina) 2. dec innervation (motor n dmg) 3. dec blood flow 4. dec nutrients 5. inc pressure (nephrolithiasis) 6. occlusion of secretory ducts (cystic fibrosis) |
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What are charactistics of inflammation? What are the causes of these?
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Charac by rubor (redness), dolor (pain), calor (heat), tumor (swelling), functio laesa (loss of func)
1. get fluid exudate fr vascular permeability, vdil, endothel injury 2. get fibrosis fr fblast emigration and prolif c deposition of extracell matrix |
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What are the different ways that inflammation can resolve?
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restoration of nml structure
granular tissue--highly vascularized, fibrotic abcess--fibrosis surrounding pus fistula--abn communication scarring--collagen deposition resulting in altered struc and func |
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What is the difference in acute and chronic inflammation wrt cell infiltrate?
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Acute: nphil, eos, Ab mediated; lasts minutes to days
Chronic: mononuclear cell mediated; charac by persistent destruction and repair. assoc c blood vessel prolif and fibrosis. granuloma is nodular collections of epithelioid mphages and giant cells. |
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What are the steps of leukocyte extravasation? What are the cell surface mediators at each step?
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1. rolling: sialyl Lewis Ag on leukocyte connects to E and P selectin
2. tight binding: by ICAM 1 on vasculature and LFA-1 integrin on leukocyte 3. diapedesis: leukocyte travels between endothel cells and exits blood vessel; via PECAM-1 on both the vessel and leukocyte 4. Migration: leukocyte travels through interstitium to site of injury or infection guided by chemotactic signals; these signals are bacterial products, C5a, IL-8, LTB4, kallikrein |
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What diseases occur b/c of free radical injury?
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retinopathy of prematurity
bronchopulmonary dysplasia CCl4 leading to liver necrosis (fatty change) acetaminophen Fe overload reperfusion after anoxia, esp after thrombolytic therapy |
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What are the granulomatous diseases?
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tuberculous
fungal infections syphilis leprosy cat scratch fever sarcoidosis Crohn's dz berylliosis |
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What is the pathophys of granulomatous diseases?
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Th1 cells secrete gamma interferon, activating mphages
TNF alpha from mphages induces and maintains granuloma formation anti TNF drugs can break down granulomas->disseminated dz T cells secrete IFN gamma, mphages secrete TNF alpha --> granuloma |
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WHat are features of an exudate vs a transudate?
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Transudate:
hypocellular protein poor specific gravity < 1.012 due to inc hydrostatic pressure, dec oncotic pressure, Na retention Exudate: cellular protein rich specific gravity > 1.020 due to lymphatic obstruction, inflammation |
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What increases and decreases ESR?
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products of inflammation (eg fibrinogen) coat RBCs and cause aggregation -> sediment at faster rate
Inc ESR: in infections, inflammation, cancer, pregnancy, SLupus Dec ESR: sickle cell (altered shape), polycythemia (too many), CHF (unknown) |
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What is mechanism and sx of iron poisoning?
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mech: cell death due to peroxidation of membrane lipids
Sx: acute: gastric bleeding chronic: metabolic acidosis, scarring that leads to GI obstruction |
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What are the types of amyloidosis, and what types of protein do they involve?
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1. primary--AL prot derived fr IgL chains
2. secondary--AA prot derived fr serum amyloid-assoc SAA prot, an acute phase reactant (in chronic inflammatory dz) 3. senile cardiac--transthyretin, derived fr AF 4. DM type 2--amylin, fr AE 5. medullary carcinoma of thyroid--A-CAL fr calcitonin 6. Alzheimer's dz--beta amyloid fr amyloid precursor protein 7. dialysis-assoc--beta2 microglobulin, fr MHC class 1 |
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What are differences seen in hypovolemic/cardiogenic shock vs septic shock?
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Hypovolemic/cardiogenic shock:
low output failure inc TPR low CO cold, clammy pt Septic shock: high output failure dec TPR dilated arterioles, high venous return hot pt |
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What are the steps of neoplastic progression?
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Nml: ysh basal -> apical diff'n
Hyperplasia: cells inc in number (hyperplasia); ysh abn prolif of cells c loss of shape, size, and orientation (dysplasia) In situ carcinoma: neoplastic cells have not invaded basement membrane, ysh high N:C ratio c clumped chromatin, neoplastic cells encompass entire thickness, tumor cells are monoclonal Invasive carcinoma: cells invade basement membrane using collagenases and hydrolases; can mets if they reach blood or lymph vessels Metastatic focus: spread to distant organ; must survive immune attack; see inc cadherin, inc laminin, inc integrin Rs, angiogenesis allows for tumor survival |
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What is hyperplasia, metaplasia, dysplasia, anaplasia, neoplasia, and desmoplasia?
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hyperplasia: inc in number of cells
metaplasia: one adult cell type is replaced by another, oft secondary to irritation or environ exposure dysplasia: abn growth c loss of cellular orientation, shape, and size in comparison to nml tissue; commonly preneoplastic anaplastic: abn cells lacking diff'n, oft undiff'n malignant neoplasms; little or no resemblance to tissue of origin neoplasia: clonal prolif of cells that is uncontrolled and excessive desmoplasia: fibrous tissue formation in response to neoplasm |
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What is tumor grade vs. stage?
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tumor grade: degree of cell diff'n based on histologic appearance of tumor; usu graded 1-4 based on degree of diff'n and number of mitoses in high power field
stage: degree of localization/spread based on site and size of primary lesion, spread to regional lymph nodes, presence of mets, spread of tumor in a specific pt |
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What neoplasms are assoc c Down syndrome?
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ALL, AML
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What neoplams are assoc c xeroderma pigmentosum and albinism?
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melanoma, BCC, and esp SCC of skin
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What neoplams are assoc c chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants?
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gastric adenocarcinoma
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What neoplams are assoc c tuberous sclerosis?
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= facial angiofibroma, seizures, mental retardation
astrocytoma, angiomyolipoma, cardiac rhabdomyoma |
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What neoplams are assoc c actinic karatosis?
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SCC
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What neoplams are assoc c Barrett's esophagus?
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esophageal adenocarcinoma
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What neoplams are assoc c Plummer Vinson syndrome?
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=atrophic glossitis, esophageal webs, anemia all due to Fe deficiency
SCC of esophagus |
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What neoplams are assoc c cirrhosis
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HCC
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What neoplams are assoc c ulcerative colitis?
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colonic adenocarcinoma
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What neoplams are assoc c Paget's dz of bone?
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secondary osteosarcoma and fibrosarcoma
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What neoplams are assoc c immunodeficiency
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malignant lymphomas
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What neoplams are assoc c AIDS
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aggressive malignant lymphomas (NHL) and Kaposi's
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What neoplams are assoc c autoimmune dz (eg Hashimotos, myesthenia gravis)
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lymphoma
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What neoplams are assoc c acanthosis nigricans?
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visceral malignancy (stomach, lung, breast, uterus)
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What neoplams are assoc c dysplastic nevus?
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malignant melanoma
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What neoplams are assoc c radiation exposure
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sarcoma, papillary thyroid cancer
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What tumors and gene products are assoc c abl oncogene?
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CML
tyrosine kinase |
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What tumors and gene products are assoc c c-myc
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Burkitt's lymphoma
transcription factor |
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What tumors and gene products are assoc c bcl-2?
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follicular and undiff'n lymphomas (inhibits apoptosis)
anti-apoptotic molecule |
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What tumors and gene products are assoc c erb-B2?
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breast, ovarian, gastric carcinomas
tyrosine kinase |
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What tumors and gene products are assoc c ras?
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colon carcinoma
GTPase |
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What tumors and gene products are assoc c L-myc?
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lung tumor
transcription factor |
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What tumors and gene products are assoc c n-myc?
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neuroblastoma
transcription factor |
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What tumors and gene products are assoc c ret?
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multiple endocrine neoplasia (MEN)
tyrosine kinase |
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What tumors and gene products are assoc c c-kit?
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gastrointestinal stromal tumor
cytokine R |
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What tumors and gene products are assoc c Rb (13q)?
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retinoblastoma, osteosarcoma
Rb prot blocks G1->S phase of cell cycle |
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What tumors and gene products are assoc c p53 (17p)?
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most human cancers, Li-Fraumeni syndrome
p53 gene product blocks G1->S phase of cell cycle |
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What tumors and gene products are assoc c BRCA1 (17q)?
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breast and ovarian cancer
DNA repair prot |
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What tumors and gene products are assoc c BRCA2 (13q)
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breast cancer
DNA repair prot |
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What tumors and gene products are assoc c p16 (9p)?
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melanoma
tumor suppressor gene |
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What tumors and gene products are assoc c APC (5q)
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colorectal ca (assoc c FAP)
tumor suppressor gene |
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What tumors and gene products are assoc c WT1 (11p)
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Wilms tumor
tumor suppressor gene |
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What tumors and gene products are assoc c NF1 (17q)
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Neurofibromatosis type 1
tumor suppressor gene |
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What tumors and gene products are assoc c NF2 (22)
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neurofibromatosis type 2
tumor suppressor gene |
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What tumors and gene products are assoc c DPC (18q)?
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pancreatic Cancer
tumor suppressor gene |
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What tumors and gene products are assoc c DCC (18q)?
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colon cancer
tumor suppressor gene |
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What tumor marker used for prostate carcinoma (and BPH and prostatitis)?
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PSA
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What tumor marker used for prostate carcinoma only?
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Prostatic acid phosphatase
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How to use CEA?
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v nonspecific but prod by 70% of colorectal, pancreatic cancers
also prod by gastric, breast, thyroid medullary carcinomas |
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What is alpha fetoprotein a tumor marker for?
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HCC
nonseminomatous germ celll tumors of testis (aka yolk sac tumors) |
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What is beta hCG a tumor marker for?
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hydatidiform moles
choriocarcinomas gestational trophoblastic tumors |
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What is CA-125 a tumor marker for?
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ovarian
malignant epithelial tumors |
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What is S-100 a tumor marker for?
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melanoma
neural tumors astrocytomas |
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What is alkaline phosphatase a tumor marker for?
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mets to bone
obstructive biliary dz Paget's dz of bone |
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What is bombesin a tumor marker for?
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neuroblastoma
lung and gastric ca |
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What is TRAP a tumor marker for?
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=tartrate R acid phosphatase
hairy cell leukemia (B cell neoplasm) |
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What is CA-19-9 a tumor marker for?
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pancreatic adenocarcinoma
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What is calcitonin a tumor marker for?
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thyroid medullary carcinoma
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What cancers are assoc c EBV?
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Burkitt's lymphoma
nasopharyngeal carcinoma Hodgkin lymphoma |
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What cancers are assoc c Schistosoma?
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SCC of transitional epithelium (i e bladder)
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What organs do the following toxins affect:
aflatoxin (fr Aspergillus) vinyl chloride CCl4 nitrosamines cigarette smoke asbestos arsenic naphthalene (aniline) dyes alkylating agents |
aflatoxin (fr Aspergillus): liver (HCC)
vinyl chloride: liver (angiosarcoma) CCl4: liver (centrilobular necrosis, fatty change) nitrosamines: esophagus, stomach cigarette smoke: larynx (SCC), lung (squamous and small cell lung ca), kidney (RCC), bladder (transitional cell carcinoma) asbestos: lung (mesothelioma and bronchogenic carcinoma) arsenic: skin (SCC), liver (angiosarcoma) naphthalene (aniline) dyes: bladder (transitional cell carcinoma) alkylating agents: blood (leukemia) |
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What are paraneoplastic syndromes assoc c small cell lung cancer?
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ACTH or ACTHrp
ADH LEMS |
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What are paraneoplastic syndromes assoc c intracranial neoplasms?
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ADH
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What are paraneoplastic syndromes assoc c squamous cell lung cancer?
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PTHrP, TGF beta, TNF, IL-1
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What are paraneoplastic syndromes assoc c renal cell carcinoma?
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PTHrP, TGF beta, TNF, IL-1, erythropoietin
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What are paraneoplastic syndromes assoc c breast carcinoma?
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PTHrP, TGF beta, TNF, IL-1
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What are cancers assoc c paraneoplastic erythropoietin?
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RCC, hemangioblastoma, HCC, pheo
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What cancers cause LEMS paraneoplastically?
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=Abs vs presynaptic Ca channel
thymoma, sm cell lung carcinoma |
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What paraneoplastic syndrome is assoc c leukemias and lymphomas?
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get hyperuricemia fr excess nucleic acid turnover -> gout, urate nephropathy
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What are psammoma bodies? When are they seen?
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=laminated, concentric, calcific spherules seen in:
1. papillary adenocarcinoma of thyroid 2. serous papillary cystadenocarcinoma of ovary 3. meningioma 4. malignant mesothelioma |
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What kinds of tumors metastasize to brain?
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lung, breast, skin, kidney, GI
usu well circumscribed tumors at gray/white matter junction |
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What kinds of tumors mets to liver?
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colon>stomach>pancreas>breast>lung
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What kinds of tumors mets to bone?
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prostate, thyroid, testes, breast, lung, kidney
mets from breast and prostate are most common mets are more common than primary bone tumors |
