General Path

Question 1

How does radiation kill cancer cells?

Answer 1

Free radicals & dsDNA breakage

Question 2

What is the role of bcl2?

Answer 2

Binding and inhibiting Apaf-1 which normally induces Caspases.

Question 3

What happens if there is a mutation in Fas-FasL interaction?

Answer 3

Autoimmune disease due to Auto-reactive Tcells in circulation from Loss of Negative selection in thymus.

Question 4

What are the nonreversible cell injury changes?

Answer 4

Nuclear pyknosis, karyolysis, karyorrhexis
Ca influx- activate Caspases
Plasma membrane damage
Lysosomal rupture
Mitochondrial permeability

Question 5

what is the FIRST sign of Shock?

Answer 5

Tachycardia

Question 6

What are the characteristics of Chromatolysis?

Answer 6

Axonal damage and repair
Round cellular swelling
Nucleus displaced in Periphery
Dispersion of Nissl substance

Question 7

Leukocyte extravasation:
Rolling
Tight binding
Diapedesis
Migration

Answer 7

Rolling= E/P selecting –> Sial-Lewisx/ Lselectin
Binding= ICAM/VCAM-> CD18/ LFA1/ VLA4 itgrn
Diapedesis-> PECAM1 –> PECAM (CD31)
Migration-> C5a/IL8/LTB4/Kallikrein

Question 8

What is the MOA of free radical damage?

Answer 8

Lipid peroxidation
Protein modification
DNA breakage

Question 9

What are some examples of free radical damage?

Answer 9

Retinopathy of prematurity 
Bronchopulmonary dysplasia
Carbon tetrachloride
Acetaminophen
Iron overload
Reperfusion

Question 10

What are the 2 types of abnormal scar formation?

Answer 10

Hypertrophic -> inc Collagen in parallel and confined boarders
Keloid = High inc Collagen and disorganized beyond boarders

Question 11

What are the tissue mediators of Wound healing and their actions?

Answer 11

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

Question 12

What cells mediate the different phases of wound healing:
Inflammatory
Proliferative
Remodeling

Answer 12

Inf–> Platelets, PMNs, Macrophages
Prolif-> Fibroblasts, myofibroblasts, endothelial cells, Keratinocytes, Macrophages
Remodeling -> Fibroblasts

Question 13

Time line for wound healing characteristics:
Immediate- 24hrs
2-3 days
1 wk

Answer 13

0-24 -> Clots, permeability, PMNs
2-3d -> Granulation, Angiogenesis, Dissolution of Clot, Wound Contraction
1wk-> T3 collagen replaced with T1, scar

Question 14

What is the mechanism of cell death due to Iron poisoning?

Answer 14

Free radicals–> Peroxidation of lipid membrane

Question 15

Amyloidosis types:
AL
AA
Dialysis
Heritable 
Senile
Organ specific

Answer 15

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

Question 16

What is the mechanism of decreased chemotheraputic response by some cancer cells?

Answer 16

P-glycoprotein (MDR1) -> PUMP it out

Question 17

What are the reversible vs irreversible changes of cancerous change?

Answer 17

Reversible: 
Hyperplasia-> inc # 
Metaplasia-> 
Dysplasia-> pleomorphic, abnormal growth
IRREVERSIBLE;
Anaplasia-> undifferentiated (Giant cells)
Neoplasia-> Clonal proliferation
Desmoplasia-> Fibrosis

Question 18

Grade vs Stage?

Answer 18

Grade-> histological appearance

Stage-> Spread (Better prognostic factor)

Question 19

What are the Carcinomas that DO NOT spread via lymphatics but hematogenously?

Answer 19

Renal cell
Hepatocellular
Follicular carcinoma of thyroid
Choriocarcinoma

Question 20

Characteristics of Benign vs malignant lumps?

Answer 20

benign= well demarcated, low mitotic activity, NO necrosis

Malignant-> locally invasive, Upregulation of telomeres prevents cell death,

Question 21

What cell mediators are involved in Cachexia?

Answer 21

TNF
IL-6
IFN gamma

Question 22

Associations with what cancer: 
Acnathosis nigricans 
Actinic keratosis
Cushing 
Dermatomyositis
Hypercalcemia
MG + PRCA 
Pagets disease of bone
Plummer vinson 
Polycythemia
Radiation exposure

Answer 22

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

Question 23

What are the gene products: 
BCR-ABL
BRAF
c-kit
HER2/neu
ras
ret

Answer 23

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

Question 24

MC tumor suppressor genes and tumors?

Answer 24

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

Question 25

Tumor markers: 
ALP
AFP
B hCG
CA 15-3
CA 19-9
CA 125
Calcitonin
CEA
S100
TRAP

Answer 25

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)