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when regulating factor is withdrawn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
Q

cellular component of chronic inflammation?

A

mononuclear cell
fibroblast

    • assoc with blood vessel prolif, fibrosis
    • can lead to scarring or amyloidosis
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26
Q

what is chromatolysis?

A

what happens to neuronal cell body following axonal injury
increased protein synthesis

findings: round cellular swelling, nuclear peripheralization, Nissl dispersal throughout cytoplasm

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27
Q

what is dystrophic calcification?

A

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

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28
Q

what is metastatic calcification?

A

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

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29
Q

what signaling molecules mediate leukocyte margination/rolling?

A

on stroma/vasculature: E-selectin, P-selectin, GlyCAM1, CD34

on leukocyte: Sialyl-Lewis, L-selectin

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30
Q

what signaling molecules mediate leukocyte tight-binding?

A

on stroma/vasculature: ICAM1 (CD54), VCAM1 (CD106)

on leukocyte: CD11/18 (LFA1, Mac1), VLA4

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31
Q

what signaling molecules mediate leukocyte diapedesis?

A

PEDCAM1 (CD31) on vasculature/stroma AND on leukocytes

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32
Q

what signaling molecules mediate leukocyte migration?

A

vasculature/stroma: release C5a, IL-8, LTB4, kallikrein, platelet activating factor

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33
Q

what step of leukocyte extravasation is deficient in LAD2?

A

decreased Sialyl Lewis –> defective margination and rolling

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34
Q

what step of leukocyte extravasation is deficient in LAD1?

A

decreased CD18 subunit –> defective tight-binding

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35
Q

how do free radicals damage cells?

A

membrane lipid peroxidation
protein modification
DNA breakage

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36
Q

what can eliminate free radicals?

A

scavenging enzymes (catalase, superoxide dismutase, glutathione peroxidase)
spontaneous decay
antioxidants (vit A,C,E)
metal carrier proteins (ceruloplasmin, transferrin)

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37
Q

by when has a scar regained 70-80% of tensile strength?

A

3 months

doesn’t regain much additional after that

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38
Q

secreted by platelets and macrophages, induces vascular remodeling and smooth mm cell migration, stimulates fibroblast growth?

A

PDGF

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39
Q

stimulates angiogenesis?

A

FGF

VEGF

40
Q

stimulates cell growth via tyrosine kinases?

A

EGF

** e.g. EGFR

41
Q

stimulates angiogenesis, fibrosis, cell cycle arrest?

A

TGF-beta

42
Q

stimulates tissue remodeling?

A

metalloproteinases

43
Q

inflammatory phase of wound healing?

A

up to 3 days after injury
clot formation, increased vessel permeability, neutrophil migration
macrophages clear debris 2 days later

** platelets, neutrophils, macrophages

44
Q

proliferative phase of wound healing?

A

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
Q

remodeling phase of wound healing?

A

1 week - 6 months after injury
type III collagen –> type I collagen
tensile strength of tissue increases

** fibroblasts

46
Q

mechanism of granuloma formation?

A

TH1 cells –> IFN-gamma –> macrophage activation

macrophages –> TNF-alpha –> induces and maintains granuloma formation

47
Q

what things cause decreased ESR?

A
sickle cell
polycythemia
HF
microcytosis
hypofibrinogenemia
48
Q

what things cause increased ESR?

A
anemia
infection
inflammation
cancer
preg
autoimmune
49
Q

deposition of proteins from Ig light chains?

A

AL (primary amyloidosis)
can be plasma cell disorder orassociated with multiple myeloma

** cardiac, renal, hematologic, GI, neurologic involvement

50
Q

deposition of fibrils composed of serum amyloid A?

A

AA (secondary amyloidosis)

seen with chronic inflammatory conditions - RA, IBD, spondyloarthropathy, infx

51
Q

beta-2 microglobulin fibril deposition?

A

dialysis-related amyloidosis

** may present as carpal tunnel syndrome

52
Q

transthyretin gene mutation?

A

heritable amyloidosis

53
Q

deposition of normal transthyretin in myocardium (and elsewhere)?

A

age-related systemic amyloidosis

** slower progression of cardiac dysfunction relative to AL

54
Q

islet amyloid polypeptide?

A

(IAPP)
commonly seen in DM2
deposition of amylin in pancreatic islets

55
Q

yellow-brown wear-and-tear pigment?

A

associated with normal aging

formed by oxidation and polymerization of autophagocytosed organellar membranes

56
Q

cellular mechanism of invasive carcinoma?

A

collagenases and hydrolases (metalloproteinases) –> basement membrane invasion
inactivation of E-cadherin –> loss of cell-cell contacts

57
Q

pumps out toxins, including chemo agents?

A

MDR1 = P-glycoprotein

classically in adrenal cell carcinoma

58
Q

what factors mediate cachexia?

A

TNF-alpha
IFN-gamma
IL-1
IL-6

59
Q

what do dermato/polymyositis predispose to?

A

visceral malignancies

esp genitourinary

60
Q

what do xeroderma pigmentosum and albinism predispose to?

A

squamous cell carcinoma
basal cell carcinoma
melanoma

61
Q

bcr-abl?

A

tyr kinase

assoc with CML and ALL

62
Q

bcl-2?

A

anti-apoptotic

assoc with follicular and undifferentiated lymphomas

63
Q

braf?

A

serine/threonine kinase

assoc with melanoma and NHL

64
Q

c-kit?

A

cytokine receptor

assoc with GIST

65
Q

c-myc?

A

transcription factor

assoc with Burkitt lymphoma

66
Q

her2neu?

A

tyrosine kinase

assoc with breast, ovarian, gastric a

67
Q

l-myc?

A

transcription factor

assoc with lung tumors

68
Q

n-myc?

A

transcription factor

assoc with neuroblastoma

69
Q

ras?

A

GTPase

assoc with colon, lung, pancreatic ca

70
Q

ret?

A

tyrosine kinase

assoc with MEN2A/2B, medullary thyroid ca

71
Q

apc?

A

colorectal cancer, assoc with FAP

72
Q

dcc?

A

dcc - deleted in colon cancer

73
Q

dpc4/smad4?

A

dpc - deleted in pancreatic cancer

74
Q

men1?

A

menin - MEN1

75
Q

nf1?

A

Ras GTPase activating protein - neurofibromin

76
Q

nf2?

A

merlin (schwannomin) protein

77
Q

p16?

A

cyclin-dependent kinase inhibitor 2a

assoc with melanoma

78
Q

p53?

A

TF for p21 - blocks G1–>S

assoc with Li-Fraumeni

79
Q

pten?

A

breast ca
prostate ca
endo ca

80
Q

rb?

A

inhibits E2F, blocks G1–>S

assoc with retinoblastoma, osteosarcoma

81
Q

TSC1/TSC2?

A

hamartin/tuberin protein

assoc with tuberous sclerosis

82
Q

vhl?

A

inhibits hypoxia inducible factor 1a

assoc with VHL, renal cell carcinoma

83
Q

alpha-fetoprotein is marker for?

A

HCC
hepatoblastoma
yolk sac tumor
mixed germ cell tumor

84
Q

Ca 15-3, CA 27-29 is marker for?

A

breast cancer

85
Q

CA 19-9 is marker for?

A

pancreatic adenocarcinoma

86
Q

CA 125 is marker for?

A

ovarian cancer

87
Q

calcitonin is marker for?

A

medullary thyroid carcinoma

88
Q

CEA is marker for?

A

carcinoembryonic antigen - produced by 70% CRC and pancreatic ca; gastric, breast, medullary thyroid carcinomas

89
Q

chromogranin is marker for?

A

neuroendocrine tumors, carcinoid

90
Q

psammoma bodies?

A

papillary carcinoma of thyroid
serous papillary cystadenocarcinoma of ovary
meningioma
malignant mesothelioma

91
Q

cancer incidence in male/female?

A

male: prostate > lung > colon
female: breast > lung > colon

92
Q

cancer mortality in male/female?

A

male: lung > prostate > colon
female: lung > breast > colon

93
Q

MC source of mets in brain?

A

lung > breast > prostate > melanoma > GI

** commonly at gray/white matter junction

94
Q

MC source of mets in liver?

A

colon&raquo_space; stomach > pancreas

95
Q

MC source of mets in bone?

A

prostate, breast > lung, thyroid, kidney