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1

what pathways does apoptosis have

intrinsic and extrinsic pathways

2

general occurrences during apoptosis (4)

1. eosniphilic cytoplasm
2. cell shrinkage
3. karyorrhexis (nuclear fragmentation)
4. apoptotic bodies

3

what happens in karyorrhexis?

endonucleases cleave at internucleosomal regions into 180bp fragments

4

what does radiation therapy do to cells

free radicals and dsDNA breakage --> apoptosis of tumors and surrounding tissue

5

when does intrinsic pathway apoptosis occur? (3)

1. regulating factor taken away from proliferating cells
2. after injurious stimuli
3. anti/pro apoptotic factor ratio

6

examples of intrinsic pathway apoptosis (4)

1. removal of IL-2 after completed immuno reaction
2. radiation, toxins, hypoxia
3. BAX and BAK (pro-apoptotic)
4. Apaf-1 (pro-apoptotic)

7

pro-apoptotic factors (3)

BAX
BAK
Apaf-1

8

anti-apoptotic facotrs (1)

1. Bcl-2

9

What does Bcl-2 do

binds to Apaf-1 and inhibits it so that it cannot release cytochrome C

10

too much bcl-2?

too little apaf-1 and you get tumorgenesis (ex follicular lymphoma)

11

what mechanism is extrinsic pathway apoptosis?

1. ligand receptor
FasL to Fas (CD95)

12

CD95?

Fas

13

thymus negative selection is what pathway of apoptosis

extrinsic pathway

14

necrosis definitino

enzymation degradation and protein denaturation 2/2 exogenous injury

15

where does coagulative necrosis occur (3)

tissue supplied by end-arteries
1. heart
2. liver
3. kidney

16

order of what happens in coagulative necrosis

1. proteins degrade first
2. enzymatic degradation

17

where does liquefactive necrosis occur and when

occurs in CNS 2/2 high fat content

brain bacterial abscess

18

order of what happens in liquefactive necrosis

1. enzymatic degradation from lysosomal release
2. Then protein degradation

19

when does caseous necrosis occur (3)

1. TB
2. systemic fungi
3. nocardia

acid fast?

20

where does fatty necrosis occur (2)

1. pancreas
2. breast

21

pancreatitis leads to what?

saponification
fatty necrosis

22

what does fatty necrosis look like on staining

calcium deposits appear dark blue

23

what does fibrinoid necrosis look like on stain

amorphous and pink on H&E

24

where can you see fibrinoid necrosis? (2)

vessels
1. vasculitidies (HSP, churg-strauss)
2. malignant HTN

25

types of gangrenous necrosis

1. dry
2. wet

26

when is there dry gangrenous necrosis

ischemic coagulative

27

when is there wet gangrenous necrosis

infection

28

common locations for gangrenous necrosis (2)

1. limbs
2. GI tract

29

Examples of causes of atrophy (7)

1. low endogenous hormones (post-menopause ovaries)
2. high exogenous hormones (thyroid, steroids)
3. low innervation (MN damage)
4. low blood flow/nutrients
5. low metabolic demand (paralysis)
6. high pressure (nephrolithiasis)
7. occlussion of secretory ducts (CF)

30

Examples of reversible cell injury (7)

1. ATP depletion
2. cellular/mito swelling 2/2 ATPase dysfunction
3. ribosome detachment 2/2 swelling
4. MB blebbibg 2/2 swelling
5. nuclear chromatin clumping
6. low glycogen
7. fatty change

31

Examples of irreversible cell injury (4)

1. nuclear pyknosis, karyorrhexis, karyolysis
2. plasma MB damage
3. lysosomal rupture
4. mitochondrial permeability/vacuolization

32

Examples of damage from ROS (6)

1. retinopathy of prematurity
2. bronchopulmonary dysplasia
3. CCl4 --> liver necrosis and fatty change
4. Acetaminophen o/d
5. Fe overload
6. Reperfusion injury esp after thrombolytic therapy

33

ischemia susceptible region of heart

subendocardium (LV)

34

ischemia susceptible region of kidney (2)

1. straight segment of proximal tubule (medulla)

2. thick ascending limb (medulla)

35

ischemia susceptible region of liver

area around central vein (zone III)

36

ischemia susceptible region of colon (2)

1. splenic flexure
2. rectum

37

chromatolysis ... what is it?

attempt at increasing protein synthesis following axonal damage

38

what do you see in chromatolysis? (3)

1. round cellular swelling
2. displacement of nucleus to periphery
3. dispersion of RER throughout cytoplasm

39

what does nissl substance stain?

RER

40

red infarct from what

hemorrhagic

41

where does red infarct occur? (3)

loose tissue with multiple blood supplies

1. liver
2. lungs
3. intestines

Red = Reperfusion

42

pale infarct where (3)

solid tissue with single blood supply

1. heart
2. kidney
3. spleen

43

distributive shock
- TPR
- CO/venous return
- PCWP

low TPR
high CO/venous return
low PCWP

44

what does distributive look like?

warm dry skin 2/2 vasodilation

need to use pressors b/c unresponsive to fluids 2/2 vasodilation

45

Cardiogenic shock
- TPR
- CO/venous return
- PCWP

high TPR
low CO/venous return
elevated PCWP

46

Hypovolemic shock
-TPR
-CO/venous return
-PCWP

high TPR
low CO/venous return
decreased PCWP

47

treating cardiogenic/hypovolemic shock

responds to fluids

48

Acute cellular inflammatory response
- onset time
- duration time

- seconds-minutes
- lasts minutes to days

49

Acute cellular inflammatory response
- involved cells
- what happens

- neutrophils, eosinophil, Ab-mediated

- resolution, abscess formation, progression to chronic inflammation

50

Chronic cellular inflammatory response
- cells involved
- what happens

- mononuclear cells and fibroblasts for persistent destruction and repair

- granuloma (nodular collection of epithelioid macrophage and giant cells)
- scarring and amyloidosis

51

what is it that leads to increased ESR in inflammation

fibrinogen coats RBCs and causes them to aggregate

52

high ESR states (5)

1. most anemias
2. infection
3. cancer (MM)
4. pregnancy
5. autoimmune d/o

53

low ESR states (3)

1. sickle cell (shape lowers ESR)
2. polycythemia (dilute)
3. CHF (unknown reason)

54

4 steps of leukocyte extravasation

1. margination and rolling
2. tight-binding
3. diapedesis
4. migration through interstitium

55

factors involved in leukocyte margination and rolling
- cellular to endothelial interaction

cellular to endothelial reaction:

- Sialyl-Lewis ...P-selectin
- Sialyl-Lewis ...E-selectin
- L-selectin ... GlyCAM-1 and CD34

56

factors involved in leukocyte tight-bonding

- cellular to endothelial interaction

- CD11/18 integrins (LFA-1, Mac-1) ... ICAM-1 (CD54)

- VLA-4 integrin ... VCAM-1 (CD106)

57

factors involved in leukocyte diapedesis

- cellular to endothelial interaection

- PECAM-1 (CD31) ... PECAM -1 (CD31)

58

factors involved in leukocyte migration

-cellular to endothelial interaction

- various things ... chemotaxis mediated through C5a, IL-8, kalligkrein, Plt-activating factor

59

examples of exudate causing stuff (4)

1. lymphatic obstruction
2. inflammation
3. infection
4. maligancy

60

examples of transudate causing stuff (3)

1. CHF (hydrostatic pressure)
2. cirrhosis (decresaed oncotic pressure)
3. Na retention

61

what's the specific gravity number differentiating exudate and transudate

1.012

62

phases of wound healing (3)

when do they occur

1. inflammatory (immediate)
2. proliferative (2-3 days)
3. remodeling (1 week later)

63

what does EGF do in wound healing

stimulates cell growth via TyrKin Rec

64

TGF-beta does what in wound healing (3)

angiogenesis
fibrosis
cell cylce arrest

65

PDGF does what in wound healign (3)

1. vascular remodeling
2. SMC migration
3. stimulate fibroblast growth for collagen synthesis

66

cells involved in inflammatory wound healing (3)

1. platelets
2. neutrophils
3. macrophages (a little later just to clean up)

clotters and eaters

67

cells involved in proliferative wound healing (5)

1. fibroblasts
2. myofibroblasts
3. endothelial cells
4. keratinocytes
5. macrophages

the rebuilders, supporters, and clean up

68

cells in remodeling wound healing

fibroblasts

69

what collagen stuff happening in wound healing

collagen III replaced by collagen I --> increases tensile strength of tissue

70

pathogenesis of granulomatous disease

TH1 cells secrete IFN-g --> activates macrophages --> they release TNF-alpha --> induces and maintains granuloma formation

71

examples of granulomatous diseases (13)

1. TB
2. Sarcoidosis
3. Crohn
4. Fungal
5. myco leprae
6. Syphilis
7. Wegener granulomatosis
8. Churg-Strauss
9. Bartonella (cat scratch)
10. Berrylliosis
11. Listeria monocytogenes
12. Francisella tularensis
13. schistosomiasis

72

types of calcification (2)

1. dsytrophic
2. mestastatic

73

dystrophic calcification caused by what

local deposits 2/2 necrosis

74

calcium state in dystrophic calcification

usually normocalcemic
not a/w hyper-Ca

75

metastatic calcification caused by what

diffuse deposits 2/2 hypercalcemia OR
high calcium-phosphate product

76

states of hypercalcemia (3)

1. primary hyperparathyroidism
2. sarcoidosis
3. hypervitamoniosis D

77

states of high calcium-phosphate product (4)

1. CRF
2. secodnary hyperparathyoriodism
3. long-term dialysis
4. warfarin

78

where is calcium usually in metastatic calcification?
- what environments
- examples

alklaloid environments

interstitial tissue of:
1. kidneys
2. lungs
3. gastric mucosa
b/c they lose acid quickly

79

how does Fe poisoning kill?

peroxidation of cell MB lipids --> cell death

80

what stains show amyloidosis

congo red stain

81

what does congo red stain look like in polarized light

apple green birefringence

82

what is primary amyloidosis ?

AL
deposits of light chains

83

causes of primary amyloidosis (AL)?

1. plasma cell d/o
2. MM

84

what does primary amyloidosis cause? (6)

1. nephrotic syndrome
2. restrictive cardiomyopathy
3. arrhyhtmia
4. easy bruising
5. hepatomegaly
6. neuropathy

85

what is secondary amyloidosis?

AA
chronic conditions with fibrils made of serum Amyloid A

86

where can you see secondary amyloidosis (4)

1. RA
2. IBD
3. Spondyloarthropathy
4. protracted infection

87

what is P-glycoprotein

MDR-1
the channel that pumps out toxins from the cell to keep it alive

88

reversible plasias (3)

hyperplasia
metaplasia
dysplasia

89

irreversible plasias (3)

anaplasia
neoplasia
desmoplasia

90

what is desmoplasia

fibrous tissue formation in response to neoplasm

91

tumor grading has to do with
- what are the numbers

differentiation and mitotic activity

1-4 from well differentiated to poorly anaplastic

92

tumor staging based on what

localization and spread

93

TNM staging involves?

tumor size
node involvement
mets

94

Carcinomas spread how

lymphatic spread

95

which carcinomas can spread hematogenously as well as lymphatically (4)

1. RCC via renal vein
2. HCC via hepatic vein
3. Follicular carcinoma of thyroid
4. Choriocarcinoma

96

sarcomas spread how

hematogenously

97

benign sarcomas 6)

1. hemangioma (vessels)
2. leiomyoma (SMC)
3. rhabdomyoma (striated muscle)
4. fibroma (connective tissue)
5. osteoma (bone)
6. lipoma (fat)

98

Cachexia is mediated by what (3)

1. TNF-alpha
2. IFN-gamma
3. IL-6

99

what is called cachectin?

TNF-alpha

100

what condition a/w visceral malignancy

acanthosis nigricans

101

what condition a/w squamous cell carcinoma of skin

actinic keratosis

102

what condition a/w malignant melanoma

dysplastic nevus (skin lesions)

103

xeroderma pigmentosum / albinism a/w what neoplasms (3)

1. melanoma
2. basal cell carcinoma
3. squamous cell carcinoma of skin

104

what condition a/w aggressive malignant non-Hodgkin lymphoma

AIDS

105

what condition a/w Kaposi sarcoma

AIDS

106

what condition a/w lymphomas

autoimmune (hashimoto, SLE)

107

what condition a/w malignant lymphomas?

immunodef

108

what condition a/w ALL and AML

Down syndrome

109

what condition a/w thymoma (2)

1. myasthenia gravis
2. pure RBC aplasia

110

what condition a/w esophageal adenocarcinoma

barrett esophagus

111

what condition a/w squamous cell carcinoma of esophagus

Plummer-Vinson syndrome (low Fe)

112

what condition a/w gastric adenocarcinoma

1. chronic atrophic gastritis
2. permicious anemia
3. postsurgical gastric remnants

113

what condition a/w colonic adenocarcinoma

UC

114

what condition a/w HCC

cirrhosis

115

what neoplasm a/w polycythemia (2)

1. RCC
2. HCC

116

what condition a/w small cell lung cancer (3)

1. Cushing
2. Lambert Eaton
3. SIADH

117

what condition a/w lung cancer

dermatomyositis

118

what condition a/w squamous cell lung cancer

hypercalcemia

119

what neoplasms a/w TS (3)

1. giant cell astrocytoma
2. renal angiomyolipoma
3. cardiac rhabdomyoma

120

what neoplasms a/w radiation exposure (4)

1. leukemia
2. sarcoma
3. papillary thyroid cancer
4. breast cancer

121

what neoplasms a/w Paget disease of bone (2)

1. secondary osteosarcoma
2. fibrosarcoma

122

examples of oncogenes (10)

1. Bcr-abl
2. bcl-2
3. BRAF
4. c-kit
5. c-myc
6. HER2/neu
7. L-myc
8. N-myc
9. Ras
10 Ret

123

what does Bcr-abl code for and what condition a/w (2)

tyrosine kinase

1. CML
2. ALL

124

what does bcl-2 code for and what condition a/w (2)

anti-apoptotic mitochondrial factor

1. follicular lymphoma
2. undifferentiated lymphoma

125

what does BRAF code for
and what condition a/w

serine/threonine kinase

melanoma

126

what does c-kit code for and what condition a/w

cytokine receptor for stem cell factor

GI stromal tumor (GIST)

127

what does c-myc code for and what condition a/w

TF

Burkitt lymphoma

128

what does HER2/neu code for and what condition a/w

tyrosine kinase

1. breast
2. ovarian
3. gastric carcinoma

129

what does L-myc code for and what condition a/w

TF

lung

130

what does N-myc code for and what condition a/w

TF

Neuroblastoma

131

what does Ras code for and what condition a/w (3)

GTPase

1. colon
2. lung
3. pancreatic

132

what does Ret code for and what condition a/w (2)

tyrosine kinase

1. MEN 2A
2. MEN 2B

133

what does BRCA1 and 2 code for and a/w (2)

DNA repair enzymes

1. breast cancer
2. ovarian cancer

134

what does CPD4/SMAD4 code for and a/w?

DPC (deleted in pancreatic cancer)

pancreatic cancer

135

what does DCC code for

deleted in colon

colon cancer

136

what does NF1 code for and a/w ?

Neurofibormin, a RAS GTPase activating protein

NF1

137

what does NF2 code for and a/w?

Merlin (schwannomin) protein

NF2

138

what does p16 code for and a./w?

cyclin-dep kinase inhibitor 2A

melanoma

139

what does p53 code for and a/w

TF for p21 ... blocks G1 to S

most cancers

Fraumeni (AR cancer syndrome): breast, leukemia, adrenal gland

140

what is PTEN and a/w?

TSG

breast, prostate, endometrial

141

what does Rb do and a/w? (2)

inhibits E2F ... blocks G1 to S

1. retinoblastoma
2. osteosarcoma

142

what genes mutated in TS

TSC1

143

VHL codes what and a/w?

inhibits hypoxia inducible factor 1a (HIF-1a)

VHL

144

AlkPhos used to monitor what (4)

1. mets to bone
2. liver disease
3. Paget disease of bone
4. seminoma (placental aklphos)

145

AFP used to monitor what (5)

1. HCC
2. hepatoblastoma
3. yolk sac (endodermal sinus) tumor
4. testicular cancer
5. mixed germ cell tumor

146

beta-hCG used to monitor what (3)

1. hydatiform moles
2. choriocarcinomas
3. testicular cancer

147

what do you use to monitor breast cancer?

CA-15/3
CA-26/29

148

what do you use to monitor pancreatic adenocarcinoma

CA-19/9

149

what do you use to monitor ovarian cancer

CA-125

150

what do you use to monitor medullary thyroid carcinoma

calcitonin

151

what are some neural crest origin cancer (4)

1. melanoma
2. neural tumo
3. schwannoma
4. Langerhans cell Histiocytosis

152

what do you use to monitor neural crest origin cancers

S-100

153

what do you use to monitor hairy cell leukemia

TRAP

154

EBV can cause what cancer

1. Burkitt lymphoma
2. Hodgkin lymphoma
3. nasopharyngeal carcinoma
4. CNS lymphoma inimmunom

155

What viruses can cause HCC? (2)

1. HBV
2. HCV

156

what virus can cause kaposi sarcoma

HHV-8

157

what causes cervical, penile, headneckthroat cancer

HPV 16,18

158

H pylori can cause what cancers (2)

1. gastric adenocarcinoma
2. MALT lymphoma

159

adult T-cell leukemias and lymphomas can be caused by what microbe

HTLV-1

160

what microbe can cause cholangiocarcinoma

liver fluke (clonorchis sinensis)

161

what microbe can cause squamous cell bladder cancer

schisotoma haematobium

162

Aflatoxin
- produced by what
- causes what cancer

- aspergillus
- HCC

163

Arsenic can cause what cancers (3)

1. angiosarcoma
2. lung cancer
3. squamous cell carcinoma

164

asbestos causes what cancer 2)

1. bronchogenic carcinoma
2. meothelioma

bronchogenic > meso

165

cigarette smoking causes what cancer (6)

1. transitional cell carcinoma
2. SCC and adenocarcinoma of esphageus
3. RCC
4. squamous cell CA or laynx
5. squamous and small cell CA of lung
6. adenocarcinoma of pancreas

166

nitrosamines
- where found
- causes what cancer

- smoked foods
- gastric cancer

167

2nd leading cause of lung cancer after smoking

Radon

168

Vinyl chloride causes what

hepatic angiosarcoma

169

what paraneoplastic syndrome a/w Hodgkin lymphoma?
- leads to

1,25-VitD --> hypercalcemia

170

what paraneoplastic syndrome a/w small cell lung carcinoma (3)

ACTH --> cushing

anti-presyn CaCh --> LES

Autoimmune subacute cerebellar degeneration --> dizzy, ataxia

171

what paraneoplastic syndrome a/w small cell lung CA and some intracranial neoplasms

ADH --> SIADH

172

what malignancies have EPO production as neoplastic syndrome? (6)

1. RCC
2. thymoma
3. hemangioblastoma
4. HCC
5. leiomyoma
6. pheochromocytoma

173

what malignances have PTHrP production as neoplastic syndrome (3)

1. squamous cell lung CA
2. RCC
3. breast cancer

174

psammoma bodies found where (4)

1. Papillary CA thyroid
2. Serous papillary cystadenoCA of ovary
3. Meningioma
4. Malignant mesothelioma

175

which mets go to brain (6)

1. lung
2. brain
3. GU
4. osteosarcoma
5. melanoma
6. GI

176

which mets go to liver

1. colon
2. stomach
3. pancreas