Pathology

Question 1

In the intrinsic pathway, what are the functions of the following…
BAX:
Bcl-2:
Apaf-1:

Answer 1

BAX: Pro-apoptotic proteins
Bcl-2: prevents cytochrome C release by binding to and inhibiting Apaf-1
Apaf-1: Normally induces the activation of caspases (unless t(14:18))

Question 2

What is the function of the Fas-FasL interaction?

Answer 2

After Fas crosslinks with FasL, multiple Fas molecules coalesce, forming a binding site for a death domain - containing an adapter protein FADD which activates caspases
- Also necessary in thymic medullary negative selection

Question 3

In coagulative necrosis ________ is first, followed by enzymatic degradation
In liquefactive necrosis enzymatic degradation is first due to release of _________ enzymes

Answer 3

In coagulative necrosis protein denaturation is first, followed by enzymatic degradation
In liquefactive necrosis enzymatic degradation is first due to release of lysozomal enzymes

Question 4

What is chromatolysis?

What are the 3 characterizations:

Answer 4

Changes following axonal injury which reflect increased protein synthesis in effort to repair the damaged axon
Characterized by:
Round cellular swelling
Displacement of nucleus to the periphery
Dispersion of nissl substance throughout the cytoplasm

Question 5

Dystrophic calcification is found in patients with ________ calcium levels
Metastatic calcification is found in patients with ________ calcium levels

Answer 5

Normal

Increased

Question 6

Extravasation occurs at __________ _________

Answer 6

Postcapillary venules

Question 7

What is responsible for tight binding during extravasation?
Vasculature:
Leukoctes:

Answer 7

Vasculature: ICAM-1 and VCAM-1
Leukoctes: CD11/18 integrins (LFA-1) and VLA-4 integrin

Question 8

What is responsible for diapedesis during extravasation?
Vasculature:
Leukoctes:

Answer 8

Vasculature: PECAM-1
Leukoctes: PECAM-1

Question 9

How does carbon tetrachloride lead to fatty liver change?

Answer 9

CCl4 produces free radicals which induce cellular injury through membrane damage (lipid peroxidation, protein modification) thus causing cellular swelling (destruction of Na/K+ pump and Ca2+ pump leads to sodium, calcium and water buildup in the cell) which leads to RER swelling to the point where ribosomes detach and thus are unable to create apolipoproteins (which remove fat from the liver) thus leading to fatty liver

Question 10

____ from macrophages induce and maintain granuloma formation

Answer 10

TNF-α

Question 11

Amyloidosis is the abnormal aggregation of proteins into __-_______ structures

Answer 11

β-pleated

Question 12

Dialysis related amyloidosis is due to fibrils composed of…

Answer 12

β-2 microglobulin

Question 13

What is desmoplasia?

Answer 13

Fibrous tissue formation in response to neoplasm (linitis plastica in diffuse stomach cancer)

Question 14

What is cachexia?

What mediates it?

Answer 14

Cachexia: Weight loss, muscle atrophy, fatigue

Mediated by TNF-α, IFN-gamma, and IL-6

Question 15

What gene product is disrupted in a ras mutation and what is it’s normal function?

Answer 15

GTPase

Normally allows RAS-GTP to become RAS-GDP which shuts off replication

Question 16

NF1 gene product:

NF2 gene product:

Answer 16

NF1 gene product: RAS-GTPase activating protein (neurofibromin)
NF2 gene product: Merlin protein (schwannomin)

Question 17

VHL gene product?

Answer 17

inhibits hypoxia inducible factor 1a

Question 18

S-100 is the tumor marker for…(more than 1)

Answer 18

Neural crest origin tumors

Melanomas, neural tumors, schwannomas, Langerhans cell histiocytosis

Question 19

When are psammoma bodies seen?

Answer 19

Papillary carcinoma of thyroid
Serous papillary cystadenocarcinoma of the ovary
Meningioma
Malignant mesothelioma

Question 20

Cancer incidence: (top 3)

Cancer mortality: (top 3)

Answer 20

Incidence: Prostate/Breast > Lung > Colon/rectum
Mortality: Lung > Prostate/Breast > Colon/rectum

Question 21

What cancers can release PTHrP?

Answer 21

Squamous cell lung carcinoma
Renal cell carcinoma
Breast cancer

Question 22

Describe the following parts of apoptosis…
Karyorrhexis:
Pyknosis:
DNA laddering:

Answer 22

Karyorrhexis: Nuclear fragmentation
Pyknosis: Nuclear shrinkage
DNA laddering: A sensitive indicator of apoptosis; during karyorrhexis, endonucleases cleave at internucleosomal regions, yielding 180-bp fragments

Question 23

Name the protein defect in the following hyperlipoproteinemias…
Familial chylomicronemia syndrome (Type I):
Hypercholesterolemia (Type II):
Dysbetalipoproteinemia (III):
Hypertriglyceridemia (IV):

Answer 23

Familial chylomicronemia syndrome (Type I): LPL and ApoC-II
Hypercholesterolemia (Type II): LDLr and ApoB-100
Dysbetalipoproteinemia (III): ApoE
Hypertriglyceridemia (IV): ApoA-V

Question 24

Name the major manifestation of the following hyperproteinemias…
Familial chylomicronemia syndrome (Type I):
Hypercholesterolemia (Type II):
Dysbetalipoproteinemia (III):
Hypertriglyceridemia (IV):

Answer 24

Familial chylomicronemia syndrome (Type I): Acute pancreatitis
Hypercholesterolemia (Type II): Premature coronary artery disease
Dysbetalipoproteinemia (III): Premature coronary artery disease
Hypertriglyceridemia (IV): Increased pancreatitis risk

Question 25

What happens with loss of the VHL tumor suppressor gene in renal cell carcinoma?

Answer 25

Increased IGF-1 (promotes growth) and increased HIF transcription factor (increases VEGF and PDGF)