general Flashcards

1
Q

end pathway of apoptosis?

A

activation of cytostolic caspases –> cellular breakdown

** ATP required

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2
Q

histologic features of apoptosis?

A
eosinophilic cytoplasm
cell and nuclear shrinkage (pyknosis)
basophilia
membrane blebbing
nuclear fragmentation (karyorrhexis)
apoptotic body formation
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3
Q

what is DNA laddering?

A

sensitive indicator of apoptosis

endonucleases cleave DNA during karyorrhexis –> fragments in multiples of 180bp

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4
Q

radiation therapy effects on tumor cells?

A

apoptosis of tumors and surroudning tissue
free radical formation
dsDNA breakage

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5
Q

intrinsic pathway of apoptosis?

A

when regulating factor is withdrawn
increase in BAX and BAK (proapoptotic), decrease in Bcl-2 (antiapoptotic)
increased mito permeability and cytochrome c release

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6
Q

Bcl-2 function?

A

binds and inhibits Apaf-1 –> prevent cytochrome c release

Apaf-1 normally induces caspase activation

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7
Q

what happens with overexpression of Bcl-2?

A

Apaf-1 overly inhibited
decreased caspase activation
tumorigenesis

** e.g. follicular lymphoma

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8
Q

extrinsic pathway of apoptosis?

A

1) FasL binds Fas (CD95) –> multiple Fas molecules coalesce –> binding site for FADD –> binds/activates caspases
2) cytotoxic T cell –> perforin and granzyme B

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9
Q

defects in Fas-FasL cause what?

A
autoimmune disorders
(needed for thymic medullary negative selection)
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10
Q

cell outlines preserved, increased cytoplasmic acidophilia?

A

coagulative necrosis
ischemia/infarcts in most tissues

** proteins denature –> enzymatic degradation

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11
Q

cellular debris and macrophages –> cystic spaces and cavitation?

A

liquefactive necrosis
bacterial abscesses, brain infarcts

** enzymatic degradation (lysosomal enzyme from neutrophils) –> proteins denature

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12
Q

fragmented cells and debris surrounded by lymphocytes and macrophages?

A

caseous necrosis
TB, systemic fungi

** macrophages wall off –> granular debris

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13
Q

outlines of dead fat cells without peripheral nuclei, dark blue on H&E?

A

fat necrosis
enzymatic (pancreatitis), nonenzymatic (breast trauma)

** cells –> lipase –> FAs in cell membranes broken down

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14
Q

thick and pink vessel walls?

A

fibrinoid necrosis
immune rxns in vessels

** immune complexes + fibrin –> vessell wall damage

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15
Q

types of gangrene?

A

ischemia –> dry gangrene – coagulative

superinfection –> wet – liquefactive

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16
Q

irreversible types of cell injury?

A

nuclear pyknosis, karyorrhexis, karyolysis
plasma membrane damage
lysosomal rupture
mitochondrial permeability/vacuolization

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17
Q

reversible types of cell injury?

A
cellular/mitochondrial swelling
nuclear chromatin clumping
decreased glycogen
fatty change
ribosomal/polysomal detachment
membrane blebbing
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18
Q

area of brain susceptible to ischemia?

A

ACA/MCA/PCA boundary - watershed

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19
Q

area of heart susceptible to ischemia?

A

subendocardium (LV)

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20
Q

areas of kidney susceptible to ischemia?

A

straight segment of prox tubule

thick ascending limb

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21
Q

area of liver susceptible to ischemia?

A

zone III - around central vein

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22
Q

area of colon susceptible to ischemia?

A

splenic flexure, rectum - watershed

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23
Q

vascular component of inflammation?

A

increased vascular permeability
vasodilation
endothelial injury

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24
Q

cellular component of acute inflammation?

A

neutrophil
eosinophil
antibody

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25
cellular component of chronic inflammation?
mononuclear cell fibroblast * * assoc with blood vessel prolif, fibrosis * * can lead to scarring or amyloidosis
26
what is chromatolysis?
what happens to neuronal cell body following axonal injury increased protein synthesis findings: round cellular swelling, nuclear peripheralization, Nissl dispersal throughout cytoplasm
27
what is dystrophic calcification?
Ca deposition in abnormal tissues 2/2 injury/necrosis usually localized ** TB, chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, Monckeberg arteriolosclerosis, congenital infx, psammoma bodies
28
what is metastatic calcification?
Ca deposition in normal tissues 2/2 hypercalcemia or high Ca-Ph levels mostly in interstitial tissues of kidney, lung, gastric mucosa - lose acid quickly, increased pH favors deposition ** hyperparathyroidism, sarcoid, hypervitaminD, renal failure, dialysis
29
what signaling molecules mediate leukocyte margination/rolling?
on stroma/vasculature: E-selectin, P-selectin, GlyCAM1, CD34 | on leukocyte: Sialyl-Lewis, L-selectin
30
what signaling molecules mediate leukocyte tight-binding?
on stroma/vasculature: ICAM1 (CD54), VCAM1 (CD106) | on leukocyte: CD11/18 (LFA1, Mac1), VLA4
31
what signaling molecules mediate leukocyte diapedesis?
PEDCAM1 (CD31) on vasculature/stroma AND on leukocytes
32
what signaling molecules mediate leukocyte migration?
vasculature/stroma: release C5a, IL-8, LTB4, kallikrein, platelet activating factor
33
what step of leukocyte extravasation is deficient in LAD2?
decreased Sialyl Lewis --> defective margination and rolling
34
what step of leukocyte extravasation is deficient in LAD1?
decreased CD18 subunit --> defective tight-binding
35
how do free radicals damage cells?
membrane lipid peroxidation protein modification DNA breakage
36
what can eliminate free radicals?
scavenging enzymes (catalase, superoxide dismutase, glutathione peroxidase) spontaneous decay antioxidants (vit A,C,E) metal carrier proteins (ceruloplasmin, transferrin)
37
by when has a scar regained 70-80% of tensile strength?
3 months | doesn't regain much additional after that
38
secreted by platelets and macrophages, induces vascular remodeling and smooth mm cell migration, stimulates fibroblast growth?
PDGF
39
stimulates angiogenesis?
FGF | VEGF
40
stimulates cell growth via tyrosine kinases?
EGF | ** e.g. EGFR
41
stimulates angiogenesis, fibrosis, cell cycle arrest?
TGF-beta
42
stimulates tissue remodeling?
metalloproteinases
43
inflammatory phase of wound healing?
up to 3 days after injury clot formation, increased vessel permeability, neutrophil migration macrophages clear debris 2 days later ** platelets, neutrophils, macrophages
44
proliferative phase of wound healing?
day 3-weeks after injury granulation tissue and collagen, angiogenesis, epithelial cell proliferation, clot dissolution, wound contraction (myofibroblasts) ** fibrolbasts, myofibroblasts, endothelial cells, keratinovytes, macrophages
45
remodeling phase of wound healing?
1 week - 6 months after injury type III collagen --> type I collagen tensile strength of tissue increases ** fibroblasts
46
mechanism of granuloma formation?
TH1 cells --> IFN-gamma --> macrophage activation | macrophages --> TNF-alpha --> induces and maintains granuloma formation
47
what things cause decreased ESR?
``` sickle cell polycythemia HF microcytosis hypofibrinogenemia ```
48
what things cause increased ESR?
``` anemia infection inflammation cancer preg autoimmune ```
49
deposition of proteins from Ig light chains?
AL (primary amyloidosis) can be plasma cell disorder orassociated with multiple myeloma ** cardiac, renal, hematologic, GI, neurologic involvement
50
deposition of fibrils composed of serum amyloid A?
AA (secondary amyloidosis) | seen with chronic inflammatory conditions - RA, IBD, spondyloarthropathy, infx
51
beta-2 microglobulin fibril deposition?
dialysis-related amyloidosis ** may present as carpal tunnel syndrome
52
transthyretin gene mutation?
heritable amyloidosis
53
deposition of normal transthyretin in myocardium (and elsewhere)?
age-related systemic amyloidosis ** slower progression of cardiac dysfunction relative to AL
54
islet amyloid polypeptide?
(IAPP) commonly seen in DM2 deposition of amylin in pancreatic islets
55
yellow-brown wear-and-tear pigment?
associated with normal aging | formed by oxidation and polymerization of autophagocytosed organellar membranes
56
cellular mechanism of invasive carcinoma?
collagenases and hydrolases (metalloproteinases) --> basement membrane invasion inactivation of E-cadherin --> loss of cell-cell contacts
57
pumps out toxins, including chemo agents?
MDR1 = P-glycoprotein | classically in adrenal cell carcinoma
58
what factors mediate cachexia?
TNF-alpha IFN-gamma IL-1 IL-6
59
what do dermato/polymyositis predispose to?
visceral malignancies | esp genitourinary
60
what do xeroderma pigmentosum and albinism predispose to?
squamous cell carcinoma basal cell carcinoma melanoma
61
bcr-abl?
tyr kinase | assoc with CML and ALL
62
bcl-2?
anti-apoptotic | assoc with follicular and undifferentiated lymphomas
63
braf?
serine/threonine kinase | assoc with melanoma and NHL
64
c-kit?
cytokine receptor | assoc with GIST
65
c-myc?
transcription factor | assoc with Burkitt lymphoma
66
her2neu?
tyrosine kinase | assoc with breast, ovarian, gastric a
67
l-myc?
transcription factor | assoc with lung tumors
68
n-myc?
transcription factor | assoc with neuroblastoma
69
ras?
GTPase | assoc with colon, lung, pancreatic ca
70
ret?
tyrosine kinase | assoc with MEN2A/2B, medullary thyroid ca
71
apc?
colorectal cancer, assoc with FAP
72
dcc?
dcc - deleted in colon cancer
73
dpc4/smad4?
dpc - deleted in pancreatic cancer
74
men1?
menin - MEN1
75
nf1?
Ras GTPase activating protein - neurofibromin
76
nf2?
merlin (schwannomin) protein
77
p16?
cyclin-dependent kinase inhibitor 2a | assoc with melanoma
78
p53?
TF for p21 - blocks G1-->S | assoc with Li-Fraumeni
79
pten?
breast ca prostate ca endo ca
80
rb?
inhibits E2F, blocks G1-->S | assoc with retinoblastoma, osteosarcoma
81
TSC1/TSC2?
hamartin/tuberin protein | assoc with tuberous sclerosis
82
vhl?
inhibits hypoxia inducible factor 1a | assoc with VHL, renal cell carcinoma
83
alpha-fetoprotein is marker for?
HCC hepatoblastoma yolk sac tumor mixed germ cell tumor
84
Ca 15-3, CA 27-29 is marker for?
breast cancer
85
CA 19-9 is marker for?
pancreatic adenocarcinoma
86
CA 125 is marker for?
ovarian cancer
87
calcitonin is marker for?
medullary thyroid carcinoma
88
CEA is marker for?
carcinoembryonic antigen - produced by 70% CRC and pancreatic ca; gastric, breast, medullary thyroid carcinomas
89
chromogranin is marker for?
neuroendocrine tumors, carcinoid
90
psammoma bodies?
papillary carcinoma of thyroid serous papillary cystadenocarcinoma of ovary meningioma malignant mesothelioma
91
cancer incidence in male/female?
male: prostate > lung > colon female: breast > lung > colon
92
cancer mortality in male/female?
male: lung > prostate > colon female: lung > breast > colon
93
MC source of mets in brain?
lung > breast > prostate > melanoma > GI ** commonly at gray/white matter junction
94
MC source of mets in liver?
colon >> stomach > pancreas
95
MC source of mets in bone?
prostate, breast > lung, thyroid, kidney