General Path Flashcards
How does radiation kill cancer cells?
Free radicals & dsDNA breakage
What is the role of bcl2?
Binding and inhibiting Apaf-1 which normally induces Caspases.
What happens if there is a mutation in Fas-FasL interaction?
Autoimmune disease due to Auto-reactive Tcells in circulation from Loss of Negative selection in thymus.
What are the nonreversible cell injury changes?
Nuclear pyknosis, karyolysis, karyorrhexis Ca influx- activate Caspases Plasma membrane damage Lysosomal rupture Mitochondrial permeability
what is the FIRST sign of Shock?
Tachycardia
What are the characteristics of Chromatolysis?
Axonal damage and repair
Round cellular swelling
Nucleus displaced in Periphery
Dispersion of Nissl substance
Leukocyte extravasation: Rolling Tight binding Diapedesis Migration
Rolling= E/P selecting –> Sial-Lewisx/ Lselectin
Binding= ICAM/VCAM-> CD18/ LFA1/ VLA4 itgrn
Diapedesis-> PECAM1 –> PECAM (CD31)
Migration-> C5a/IL8/LTB4/Kallikrein
What is the MOA of free radical damage?
Lipid peroxidation
Protein modification
DNA breakage
What are some examples of free radical damage?
Retinopathy of prematurity Bronchopulmonary dysplasia Carbon tetrachloride Acetaminophen Iron overload Reperfusion
What are the 2 types of abnormal scar formation?
Hypertrophic -> inc Collagen in parallel and confined boarders
Keloid = High inc Collagen and disorganized beyond boarders
What are the tissue mediators of Wound healing and their actions?
PDGF-> Induce vascular remodeling, smooth muscle migration, Fibroblast growth and COLLAGEN synthesis
FGF-> angiogenesis
EGF=> cell growth via TK receptor
TGFb-> Angiogenesis, FIBROSIS, cell cycle arrest
MMP-> Remodeling
What cells mediate the different phases of wound healing:
Inflammatory
Proliferative
Remodeling
Inf–> Platelets, PMNs, Macrophages
Prolif-> Fibroblasts, myofibroblasts, endothelial cells, Keratinocytes, Macrophages
Remodeling -> Fibroblasts
Time line for wound healing characteristics:
Immediate- 24hrs
2-3 days
1 wk
0-24 -> Clots, permeability, PMNs
2-3d -> Granulation, Angiogenesis, Dissolution of Clot, Wound Contraction
1wk-> T3 collagen replaced with T1, scar
What is the mechanism of cell death due to Iron poisoning?
Free radicals–> Peroxidation of lipid membrane
Amyloidosis types: AL AA Dialysis Heritable Senile Organ specific
AL-> Light chains, MM, restrictive CM/ hepatomegaly
AA-> RA/IBD/ HLAB2, multi system, CM, CNS
Dialysis-> beta 2, Carpal tunnel
Heritable-> TTR, Heart
senile-> Wile type TTR, slow progression
Organ specific-> ABeta in Alzh/ Islet Amyloid polypeptide in T2DM
What is the mechanism of decreased chemotheraputic response by some cancer cells?
P-glycoprotein (MDR1) -> PUMP it out
What are the reversible vs irreversible changes of cancerous change?
Reversible: Hyperplasia-> inc # Metaplasia-> Dysplasia-> pleomorphic, abnormal growth IRREVERSIBLE; Anaplasia-> undifferentiated (Giant cells) Neoplasia-> Clonal proliferation Desmoplasia-> Fibrosis
Grade vs Stage?
Grade-> histological appearance
Stage-> Spread (Better prognostic factor)
What are the Carcinomas that DO NOT spread via lymphatics but hematogenously?
Renal cell
Hepatocellular
Follicular carcinoma of thyroid
Choriocarcinoma
Characteristics of Benign vs malignant lumps?
benign= well demarcated, low mitotic activity, NO necrosis
Malignant-> locally invasive, Upregulation of telomeres prevents cell death,
What cell mediators are involved in Cachexia?
TNF
IL-6
IFN gamma
Associations with what cancer: Acnathosis nigricans Actinic keratosis Cushing Dermatomyositis Hypercalcemia MG + PRCA Pagets disease of bone Plummer vinson Polycythemia Radiation exposure
nigricans = Stomach cancer Actinic-> SCC of skin Cushing-> Small cell lung Dermatomyositis-> Lung cancer HyperCa--> SCC of lung MG + PRCA --> Thymoma Pagets--> Osteogenic sarcoma PVS--> SCC of esophagus Polycythemia--> RCC, Hemangioblastoma Radiation--> Leukemia, Papillary thyroid, breast cancer
What are the gene products: BCR-ABL BRAF c-kit HER2/neu ras ret
BCR-ABL --> CM Tyrosine kinase BRAF--> Melanoma Serine kinase c-kit--> GIST Cytokine receptor Her2/neu--> Breast/ ovarian TK ras--> Colon GTPase ret--> MEN2 TK
MC tumor suppressor genes and tumors?
APC--> Colorectal BRCA--> breast (DNA repair) CPD4/ SMAD4--> Pancreatic DCC--> Colon MEN1-- MEN1 NF1-> RAS GTPase activating protein NF2--> Merlin (schwannomin) protein p16--> melanoma CDK inhibitor p53--> Li fraumeni PTEN--> Breast, prostate, endometrial Rb--> Inhibits E2F VHL--> Inhibits Hypoxia induced factor Ia
Tumor markers: ALP AFP B hCG CA 15-3 CA 19-9 CA 125 Calcitonin CEA S100 TRAP
ALP--> Metastasis to bone, Pagets, Seminoma AFP-> HCC, Yolk sac/ endodermal sinus B hCG-> Choriocarcinoma, Moles CA 15-3 --> breast cancer CA 19-9--> Pancreatic cancer CA 125--> Ovarian Calcitonin-> Medullary thyroid CEA --> Colorectal S100 --> Neural crest (schwannoma, melanoma, Langerhans histiocytosis) TRAP--> Hairy cell (B cells)
