Chapter 1/2/3 Flashcards

1
Q

mechanism of hypertrophy

A

gene activation, protein synthesis and production of organelles

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2
Q

mechanism of hyperplasia

A

increase in cells from stem cells

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3
Q

permanent tissues can not undergo…..

A

hyperplasia

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4
Q

permanent tissue of body

A

cardiac/skeletal muscle and nerves

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5
Q

exception of hyperplasia to dysplasia

A

BPH

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6
Q

decrease in number of cells occurs by…

A

apoptosis

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7
Q

decrease in size of cells occurs by…

A
  • ubiquitin proteasome degradation pathway

- autophagy (in vacuoles with lysosomes)

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8
Q

mechanism for metaplasia

A

reprogramming of stem cells

- reversible by removing stress

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9
Q

exception for metaplasia to cancer

A

apocrine metaplasia

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10
Q

______ deficiency can result in metaplasia

A
vitamin A (necessary for special epithelium)
- results in thickening of conjunctiva
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11
Q

example of mesenchymal tissue metaplasia

A

myositis ossificans

  • skeletal muscle converts to bone after trauma
  • can be confused with osteosarcoma (not connected to bone)
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12
Q

is dysplasia reversible

A

YES

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13
Q

point where changes are irreversible

A

carcinoma

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14
Q

most common cause of Budd Chiari

A

polycythemia vera (also lupus)

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15
Q

what is decreased in CO poisoning

A

oxygen saturation (can’t bind to hemoglobin)

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16
Q

classic finding of CO poisoning

A

cherry red skin (also headache is early sign)

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17
Q

what is decreased in methemoglobinemia

A

oxygen saturation (iron is in Fe3+ state and cant bind to hemoglobin)

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18
Q

cause of methemoglobinemia

A

oxidant stress (sulfa and nitrate drugs) or in newborns (immature deoxidants)

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19
Q

classic finding in methemoglobinemia

A

cyanosis and chocolate colored blood

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20
Q

treatment of methemoglobinemia

A

methylene blue

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21
Q

findings of reversible injury

A

cellular swelling (water follows sodium)

  • loss of microvilli, membrane blebbing(from cytoskeletal damage) and swelling of RER
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22
Q

hallmark of irreversible damage

A

membrane damage

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23
Q

apoptosis activator

A

cytochrome C

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24
Q

three membranes damages in cell injury

A

plasma, mitochondrial, lysosome

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25
Q

hallmark of cell death

A

loss of nucleus

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26
Q

pyknosis

A

shrinking of nucleus

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27
Q

karyorrhexis

A

breaking up of nucleus

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28
Q

karylosis

A

lysing of nucleus

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29
Q

what follows necrosis

A

acute inflammation

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30
Q

coagulative necrosis

A
  • necrotic tissue remains firm, structure remains
  • nucleus disappears
  • a result of ischemic infarction (expect brain)
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31
Q

red infarction

A

if blood re enters tissue after infarction

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32
Q

liquefactive necrosis

A
  • dead tissue becomes liquid by enzymatic destruction
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33
Q

liquefactive necrosis seen in….

A
  • brain infarction (microglial cell mediated)
  • abscess (neutrophils have hydrolytic enzymes)
  • pancreatitis (of pancreas itself)
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34
Q

gangrenous necrosis

A
  • ischemia of lower limb**
  • can be GI tract
  • usually in diabetics
  • resembles mummified tissue
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35
Q

caseous necrosis

A
  • soft friable necrotic tissue
  • combination of coagulative and liquefactive necrosis
  • TB and fungal infections
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36
Q

fat necrosis

A
  • adipose tissue
  • fatty acids bind with calcium (saponification)
  • happens in pancreatitis (peripancreatic fat) and trauma to breast
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37
Q

saponification

A

fatty acids combining with calcium

- example of dystrophic calcification (nidus)

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38
Q

metastatic calcification

A

calcium or phosphate levels are high (does not mean there is cancer)
- calcium deposits in tissue

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39
Q

fibrinoid necrosis

A
  • necrotic damage of blood vessel wall, leaking of proteins
  • bright pink staining
  • characteristic of malignant hypertension and vasculitis
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40
Q

preeclampsia leads to….

A

fibrinoid necrosis of placenta

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41
Q

apoptosis is mediated by….

A

caspases

  • proteases to break down cytoskeleton
  • endonucleases break down DNA
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42
Q

intrinsic mitochondrial pathway

A
  • caused by cell injury, DNA damage or decreased hormone

- mediated by cytochrome C

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43
Q

Bcl2

A

stabilized mitochondria so cytochrome C stays in membrane

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44
Q

extrinsic apoptotic pathway

A
  • FAS ligand binds FAS receptor on target cell
  • TNF binds TNF receptor
  • causes apoptosis
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45
Q

molecules CD8 cells use

A

perforin and granzymes

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46
Q

physiologic generation of free radicals

A
  • cytochrome c oxidase transfers electrons to oxygen

- partial reduction leads to free radicals

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47
Q

most damaging free radical

A

OH

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48
Q

enzyme for producing free radical in neutrophil

A

NADPH oxidase

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49
Q

results of free radical damage

A
  • peroxidation of lipids

- oxidation of DNA and proteins

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50
Q

enzymes of free radical removal

A
  • super oxide dismutase (O2-)
  • glutathione peroxidase (OH-)
  • catalase (H2O2)
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51
Q

amyloid

A

misfolded protein that deposits in extracellular space

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52
Q

common characteristics of amyloid

A
  • beta pleated sheets

- congo red stain with apple green birefringence on polarized light

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53
Q

primary amyloidosis

A
  • AL amyloid derived from Ig light chain

- associated with plasma cell dyscrasias

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54
Q

secondary amyloidosis

A
  • AA amyloid from SAA

- acute phase reactant from inflammation, malignancy, familial Mediterranean fever

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55
Q

familial Mediterranean fever

A
  • dysfunction of neutrophils
  • leads to fever and serosal inflammation
  • High SAA during attacks and deposits of AA
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56
Q

findings of amyloidosis

A
  • nephrotic syndrome (kidney most common)
  • restrictive cardiomyopathy
  • tongue enlargement, malabsorption
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57
Q

senile cardiac amyloidosis

A
  • serum transthyretin in heart

- asymptomatic

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58
Q

familial amyloid cardiomyopathy

A
  • mutated serum transthyretin

- restrictive cardiomyopathy

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59
Q

by product of insulin

A

amylin deposits in pancrease

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60
Q

alzheimer disease

A

Abeta deposits derived from beta-amyloid precursor protein (seen in down syndrome)

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61
Q

dialysis associated amyloidosis

A

beta-2 microglobulin in joints

- not filtered well from blood

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62
Q

medullary carcinoma of thyroid

A
  • calcitonin deposits in tumor
  • c cells
  • classic for tumor cells and amyloid
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63
Q

hallmarks of acute inflammation

A

neutrophils and edema

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64
Q

CD14

A

on macrophages, recognizes LPS on gram negative bacteria

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65
Q

NF-KB

A
  • TLR binding uses this to activate immune response
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66
Q

cyclooxygenase produces…

A

prostaglandins

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67
Q

PGI2, PGD2, PGE2

A

vasodilation and increased permability

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68
Q

PGE2

A

Feeever and pain

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69
Q

LTB4

A

attracts and activates neutrophils

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70
Q

LTC4, LTD4, LTE4

A

vasoconstriction, bronchospasm, and increase vascular permeability (pericyte contraction)

  • smooth muscles contraction
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71
Q

mast cell activated by…

A
  • tissue trauma
  • C3a and C5a (anaphylatoxins)
  • IgE crosslinking
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72
Q

histamine

A
  • vasodilation of arterioles

- increased vascular permeability of post capillary venule

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73
Q

what is necessary for delayed response of mast cells

A

leukotrienes, second phase of mast cell response

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74
Q

classical pathway

A

C1 binds to IgG of IgM bound to antigen

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75
Q

alternative pathway

A

microbial products directly activate

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76
Q

C5a

A

chemotactic for neutrophils

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77
Q

C3b

A

opsonin for phagocytosis

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78
Q

4 things that attract neurotphils

A
  • LTB4
  • C5a
  • IL8
  • bacterial products
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79
Q

Hageman factor

A
  • activated on exposure to subendothelial or tissue collagen
  • important role in DIC
  • activates coag and fibrinolytic system
  • complement and kinin system
80
Q

kinin

A

like histamine and pain

81
Q

pain mediated by…

A

PGE2 and bradykinin

82
Q

fever cytokines

A

IL1 and TNF (macrophages), increase in COX

- PGE2 raises temp

83
Q

molecules in rolling

A

selectins on endothelial cells bind to neutrophils

84
Q

P selectin

A

from Weibel-Palade bodies, mediated by histamine

85
Q

E selectin

A

induced by TNF and IL1

86
Q

sialyl Lewis X

A

on leukocytes, binds to selectins during rolling

87
Q

neutrophil adhesion

A

cellular adhesion molecules on endothelial cells bind integrins on neutrophils

88
Q

defect in leukocyte adhesion deficiency

A

CD18 deficiency (integrins)

89
Q

clinical features of LAD

A
  • delayed separation of umbilical cord (no acute inflammation)
  • increased circulating neutrophils
  • recurrent infections that lack pus
90
Q

disease with delayed separation of umbilical cord

A

LAD

91
Q

chediak higashi syndrome

A
  • protein trafficking defect

- microtubule defect can’t traffic lysosome

92
Q

clinical features of chediak higashi syndrome

A
  • increased infection
  • neutropenia (cant divide properly)
  • giant granules in leukocytes
  • defective primary hemostasis (dependent on platelets)
  • albinism (pigment by melanocytes cant be handed off)
  • peripheral neuropathy (lack of transport)
93
Q

pseudomonas cepecia

A

in CGD because of catalase positivity

94
Q

MPO deficiency

A

increase of candida infection

NBT test is positive

95
Q

cytokines for resolution and healing

A

IL10 and TGF-beta (shut down inflammatory process)

96
Q

mechanisms for continued acute inflammation

A

IL8

97
Q

B7

A

on APC, binds to CD28 on CD4 T cells

28/7 = 4

98
Q

TH1

A
Helps CD8 T cells (via IL2)
helps macrophages (via IFN-gamma)
99
Q

TH2

A
IL4 (IgG to IgE)
IL5 (eosinophil activation, plasma cells, IgA class switching
IL10 (downregulates TH1)
100
Q

second signal of B cell binding

A

CD40 and CD40L

101
Q

defining feature of granuloma

A

epithelioid histiocytes

102
Q

steps in granuloma formation**

A
  • macrophages present antigen to MHC II to helper T cells
  • IL12 convert TH1
  • IFN gamma convert macrophages to histiocytes
103
Q

diGeorge syndrome

A
  • failure of 3/4 pharyngeal pouch

- no thymus or parathyroids

104
Q

SCID

A
  • both cell mediated and humoral immunity

- infections (no live vaccines)

105
Q

etiologies of SCID

A
  • cytokine receptor defects
  • ADA deficiency (toxicity to lymphocytes)
  • MHC II deficiency
106
Q

X-linked agammaglobulinemia

A
  • lack Ig
  • disordered B cell maturation
  • Bruton tyrosine kinase
  • Bacterial enterovirus and giardia***
107
Q

CVID

A
  • low Ig
  • B or T cell defect
  • bacteria, enterovirus, giardia
  • risk for autoimmue and lymphoma
108
Q

IgA deficiency

A
  • most common

- mucosal and infections, especially viral

109
Q

hyper IgM syndrome

A
  • mutation in CD40 or CD40L
  • can not class switch
  • recurrent pyogenic infections at mucosal surfaces
110
Q

Wiskott- Aldrich syndrome

A
  • thrombocytopenia
  • eczema
  • immune deficiency
111
Q

C5-C9 deficiency

A

Neisseria infections

112
Q

C1 inhibitor deficiency

A

angioedema and mucosal surfaces (periorbital)

113
Q

autoimmune polyendocrine syndrome

A

AIRE mutation (lack of central tolerance)

114
Q

AIRE

A

transcription of self antigens in thymus

115
Q

ALPS (autoimmune lymphoproliferative syndrome)

A

Fas apoptosis pathway mutation, lack of peripheral tolerance

116
Q

CD95

A

same as Fas (for apoptosis)

117
Q

CTLA4

A

binds B7, turns off system

118
Q

negative cytokines

A

IL10 and TGF beta

119
Q

CD 4 and CD 25 positive

A

Treg (also FoxP3)

120
Q

CD 25 polymorphisms

A

no IL2 receptor (leads to MS and type 1 DM)

121
Q

IPEX syndrome

A

FOXP3 mutation

122
Q

PTPN22

A

associated with autoimmunity (tyrosine phosphatase)

123
Q

lupus (SLE)

A
  • immune complexes activate complement

- early complement deficiency (C2)

124
Q

findings in SLE

A
  • fever, weight loss and fatigue
  • LAD Raynaud
  • Malar butterfly rash
  • oral/nasopharyngeal ulcers
  • arthritis and serositis
  • CNS problems
  • renal damage
  • anemia, thrombocytopenia
  • Libman-Sacks endocaditis
125
Q

antibodies in SLE

A
  • ANA (sensitive)

- anti-dsDNA or anti-Smith (specific)

126
Q

false positive syphilis test

A

anticardiolipin antibodies

127
Q

antiphospholipid antibody syndrome

A
  • antiphospholipid antibody plus hypercoagulable state

- associated with lupus but not necessary

128
Q

drugs associated with lupus

A
  • hydralazine, procainamide and isoniazid
  • ANA+
  • removal of drugs end disease
129
Q

most common causes of death in lupus

A
  • renal failure and infections
130
Q

sjogrens syndrome

A
  • type 4 hypersensitivity to lacrimal and salivary glands
  • dry mouth, dry eyes, dental caries
  • associated with RA
131
Q

anti-ribonucleoprotein antibodies

A

Sjogren’s

  • anti SSA and SSB
  • can cross placenta (neonatal lupus and congenital heart block)
132
Q

three criteria for sjogrens

A
  • dry eyes
  • Anti ANA, anti SSA, anti SSB
  • lymphocytic siadelnitis
133
Q

increased risk for……in Sjogrens

A

B-cell lymphoma

134
Q

Scleroderma

A
  • activation of fibroblasts leading to increased collagen deposition
  • produce endothelin, PDGF
135
Q

CREST

A
Calcinosis (anti-centromere)
Raynaud
Esophageal
Sclerodactyly
Telangiectasias
  • limited type shows limited skin imvolement
136
Q

diffuse scleroderma

A

CREST plus other organs

- pulmonary most common cause of death

137
Q

antibodies to diffuse and limited scleroderma

A

diffuse - DNA topoisomerase I

limited - anti-centromere antibodies

138
Q

antibodies in mixed connective tissue disease

A

ANA with serum antibodies against U1 ribonucleoprotein

139
Q

initial phase of repair

A

granulation tissue

140
Q

colagenase (and cofactor)

A

removes type 3 collagen and requires zinc

141
Q

TGF-alpha

A

epithelial and fibroblast growth factor

142
Q

TGF-beta

A
  • epithelial and fibroblast growth factor

- inhibits inflammation

143
Q

PDGF

A
  • endothelium, smooth muscle and fibroblast growth factor
144
Q

FGF

A

angiogenesis, skeletal development

145
Q

VEGF

A

angiogenesis

146
Q

mechanism for scar shrinking

A

myofibroblasts

147
Q

keloid

A

characterized by type 3 collagen

- classically in earlobe

148
Q

G6PD isoforms

A

used to determine clonality in neoplasia (can also be androgen receptor isoforms)

149
Q

aflatoxins

A
  • causes hepatocellular carcinoma

- from aspergillus from stored grains

150
Q

alkylating agents

A
  • causes leukemia/lymphoma

- side effect of chemo

151
Q

alcohol

A
  • causes SCC or oral cavity, pancreatic carcinoma and hepatocellular carcinoma
152
Q

arsenic

A
  • causes squamous cell carcinoma of skin, lung and angiosarcoma
  • in cigarette smoke
153
Q

asbestos

A
  • causes lung carcinoma and mesothelioma

- more likely to cause lung cancer

154
Q

cigarette smoke

A
  • carcinoma of oropharynx, esophagus, lung, kidney and bladder (toxins concentrated in urine)
  • polycyclic hydrocarbons
155
Q

nitrosamines

A
  • causes stomach cancer (intestinal type)

- in smoked food

156
Q

napththylamine

A
  • causes urothelial carcinoma of bladder

- from cigarette smoke

157
Q

vinyl chloride

A
  • causes angiosarcoma of liver

- used to make PVC

158
Q

nickel, chromium, beryllium or silica

A
  • causes lung carcinoma

- occupational exposure

159
Q

HHV-8

A

Kaposi sarcoma

160
Q

EBV

A
  • chinese male and african

- neck mass, Burkitt lymphoma and CNS lymphoma in AIDS

161
Q

HTLV-1

A

Adult T-cell leukemia/lymphoma

162
Q

high risk HPV

A

16,18,31,33

163
Q

ionizing radiation

A

AML, CML and papillary carcinoma of thyroid

- generates hydroxyl free radicals

164
Q

non-ionizing radiation

A
  • basal/squamous cell carcinoma and melanoma

- causes pyrimidine dimers which are excised by endonucleases

165
Q

PDGF-B (cancer)

A
  • growthy factor

- in astrocytoma, self activation (autocrine)

166
Q

ERBB2 (HER2/neu)

A
  • epidermal growth factor receptor

- breast carcinoma

167
Q

RET (cancer)

A
  • neural growth factor receptor

- MEN 2A, MEN2B, sporadic medullary carcinoma of thyroid

168
Q

KIT (cancer)

A
  • stem cell growth factor receptor

- gastrointestinal stromal cancer

169
Q

RAS (cancer)

A
  • GTP binding protein

- carcinoma, melanomas, and lymphomas

170
Q

ABL

A
  • tyrosine kinase

- CML and some types of ALL

171
Q

c-myc

A
  • transcription factor t(8:14) involving IgH

- Burkitt lymphoma

172
Q

n-myc

A
  • transcription factor

- neuroblastoma

173
Q

l-myc

A
  • transcription factor

- lung carcinoma

174
Q

CCND1

A
  • cyclin t(11:14) involving IgH

- mantle cell lymphoma

175
Q

CDK4

A
  • cyclin dependent kinase

- melanoma

176
Q

cyclin D

A

allows cell to go from G1 to S

177
Q

Rb

A

binds to E2F, when Rb is phosphorylated, E2F is released and G1 goes to S

178
Q

Bcl2

A

stabilizes mitochondrial membrane, prevents apoptosis

179
Q

what is overexpressed in follicular lymphoma

A

Bcl2, prevention of apoptosis (only place where you want a lot of apoptosis)

180
Q

downregulation of E-cadherin

A

allows tumor cells to detach from each other

181
Q

steps for tumor cells to escape

A
  1. downregulation of E-cadherin
  2. attach to laminina and destroy BM
  3. attach to fibronectin in ECM
  4. entrance into vessels
182
Q

carcinomas spread via…..

A

lymphatics

183
Q

sarcomas spread via….

A

hematogenous route

184
Q

carcinomas that go in blodd

A
  • Renal cell carcinoma (renal vein)
  • hepatocellular carcinoma (hepatic vein)
  • follicular carcinoma of thyroid
  • choriocarcinoma
185
Q

how does ovarian cancer spread

A

seeding

186
Q

keratin

A

epithelium

187
Q

vimentin

A

mesenchyme

188
Q

desmin

A

muscle

189
Q

GFAP

A

neuroglia

190
Q

neurofilament

A

neurons

191
Q

PSA

A

prostatic epithelium

192
Q

ER (estrogen receptor)

A

breast epithelium

193
Q

thyroglobulin

A

thyroid follicular cells

194
Q

chromogranin

A

neuroendocrine cells

195
Q

S-100

A

melanoma