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Cell Injury and Death > Robbins & Cottran Ch. 1+2 > Flashcards

Robbins & Cottran Ch. 1+2 Flashcards

1
Q

Which of the following is NOT a result of decrease in ATP levels (to 5-10% of normal)?

a. Failure of Ca2+ pump
b. Deceased glycogenolysis
c. Failure of plasma membrane Na/K ATPase
d. Detachment of ribosomes

A

B: there is INCREASED glycogenolysis and a switch to anerobic metabolism; all of the other processes occur and lead to cell damage/necrosis.

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2
Q

All of the following are major consequences of mitochondrial damage EXCEPT?

a. Release of cytochrome C
b. Opening of mitochondrial transition pore
c. Increased ATP production
d. Increased production of reactive oxygen species

A

C: Opening of mitochondrial permeability pore leads to loss of membrane potential and drops ATP levels.

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3
Q

Which of the following are consequences of increased cytosolic Ca2?

a. Activation of caspases
b. Opening the mitochondrial transition pore
c. Degradation of cytoskeletal proteins
d. DNA and chromatin fragmentation
e. All of the above

A

E: All of these occur. A directly induces apoptosis, b can induce apoptosis, c occurs by activating proteases, d occurs by activating endonucleases.

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4
Q

Which of the following free radicals is also an important chemical mediator for vasculature and neurons??

a. Superoxide anion
b. Hydrogen peroxide
c. Hydroxyl radical
d. Nitric oxide

A

D: Freely diffusible, causes vasodilation, acts as a neurotransmitter, can be further converted to more reactive ROS like peroxynitrite.

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5
Q

Which of the following antioxidant molecules is found within peroxisomes?

a. Superoxide dismutase
b. Catalase
c. Glutathione peroxidase
d. Lactoferrin
e. Ceruloplasmin

A

B: A and C are found in the cytosol, D is found in milk/tears/saliva/mucus, and E is a plasma protein.

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6
Q

Which of the following BCL-family molecules PROMOTES apoptosis?

a. BAX
b. BCL-2
c. BCL-XL
d. MCL1

A

A: all of the others are anti-apoptotic. BAK is the other important pro-apoptotic member of the BCL family. BAX and BAK bind and promote mitochondrial permeability. The others stabilize mitochondrial membrane stability.

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7
Q

Which is the critical initiator caspase of the intrinsic or mitochondrial pathway of apoptosis?

a. Caspase 3
b. Caspase 6
c. Caspase 8
d. Caspase 9
e. Caspase 10

A

D: Cytochrome c binds to apoptosis-activating factor 1 (Apaf-1), forming the “apoptosome” and binding caspase 9, which activates the “executioner” caspases 3 and 6 that cleave organelles, proteins and DNA. Caspases 8 and 10 are activated by the extrinsic “death-ligand” pathway, i.e. binding of FasL, TNF, etc.

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8
Q

Which of the following is NOT an established function of lncRNAs?

a. Promote chromatin modification through (de)acetylases, (de)methylases,
b. Act as scaffolding that acts on chromatin
c. Recruiting ribonucleoprotein transcription complex via transcription factor binding
d. Degrade mRNA transcripts in association with RISC

A

D (this is done by miRNAs)

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9
Q

Which of the following lipids acts as a signal for phagocytosis when it is externalized?

a. Sphingomyelin
b. Phosphatidylserine
c. Phosphatidylinositol
d. Phosphatidylcholine

A

B (PS is externalized during apoptosis)

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10
Q

Which of the following molecules does not readily cross lipid bilayers?

a. O2
b. Estradiol
c. Glucose
d. Urea

A

C (all of the others are lipid-soluble or very small)

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11
Q

Which molecular is associated with pinocytosis

a. Clathrin
b. Caveolin
c. Src-kinases
d. Folate

A

A (the others are involved in caveolae endocytosis)

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12
Q

Which of these is not a function of microtubules?

a. anterograde motor transport
b. retrograde motor transport
c. maintaining nuclear morphology and integrity
d. Forming cilia and flagella

A

C (lamins do that)

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13
Q

Which of the following transcription factors is NOT one of the key mediators of cell hypertrophy?

a. GATA4
b. MUM-1
c. NFAT
d. MEF2

A

B, MUM-1 is a transcription factor involved in differentiation of lymphoid cells, particularly plasma cells

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14
Q

Which of the following is NOT a morphologic feature of REVERSIBLE cell injury?

a. Lipid vacuolation (aka fatty change)
b. Cell swelling
c. Plasma membrane blebbing
d. Pyknosis, karyorhexis, or karyolysis
e. ER dilation and detachment of ribosomes

A

D, these nuclear changes are the hallmark of irreversible cell death and are seen with either necrosis (karyolysis), or necrosis and apoptosis (Pyknosis, karyorhexis)

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15
Q

Which of the following processes is NOT responsible for increased cell eosinophilia and glassy appearance during damage and death?

a. Appearance of myelin figures
b. Degradation of cytoplasmic RNA
c. Denaturation of cytoplasmic proteins
d. Loss of glycogen

A

A, all of the others contribute. B leads to loss of the hematoxylin-binding RNA, C leads to more proteins that bind eosin, and D leads to a smoother, glassy appearance

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16
Q

Match the type of necrosis with the associated etiology:

a. Coagulative necrosis
b. Liquefactive necrosis
c. Caseous necrosis
d. Fibrinoid necrosis

  1. Vasculitis, immune complex reactions
  2. Granulomas, i.e. Mycobacterial reactions
  3. Ischemic events
  4. Bacterial (and some fungal) infections
A

Answers: A-3, B-4, C-2, D-1

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17
Q

Which of the following statements is false regarding cardiac hypertrophy?

a. During hypertrophy, the α-myosin heavy chain is replaced with the β-myosin heavy chain.
b. Stimuli for myocardial hypertrophy include increased levels of α-adrenergic hormones, angiotensin II, and endothelins.
c. Cardiac hypertrophy is associated with the re-induction of ANF gene expression in the atria and ventricles.
d. Transcription factors involved in myocardial hypertrophy include c-Jun, c-Fos, and Egr-1.
e. Cardiomyocte hypertrophy is associated with decreased myosin ATPase activity.

A

C

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18
Q

Which of the following statements is true regarding mechanisms of cell injury?

a. Anemia results in more rapid and more severe tissue injury than thrombosis.
b. The drop in intracellular pH associated with the switch to anaerobic metabolism in ATP-depletion mediated cellular injury results in swelling of the cell, mitochrondria, and endoplasmic reticulum.
c. The formation of the mitochondria permeability transition is a marker of irreversible cell injury resulting in depletion of the membrane potential and induction of apoptosis.
d. Free radicals promote single-stranded DNA breaks, formation of disulfide bonds, and protein fragmentation.
e. None of the above are true.

A

D

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19
Q

Which of following is not a recognized player in the mechanism in the initiation of atrophy?

a. Thyroid hormone.
b. Insulin
c. Glucocorticoids
d. TNF
e. all of the above play a role in producing atrophy.

A

B

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20
Q

Which of the following is a distinction between hypoxia and ischemia?
A. Hypoxia is an important cause of cell death.
B. Ischemia injures tissues faster than hypoxia does.
C. Hypoxia impinges on oxidative aerobic metabolism.
D. Ischemic cells are often able to adapt and survive.
E. Hypoxia affects primarily cardiac and skeletal muscle.

A

B

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21
Q

All of the following are important events in the mediation of cell injury EXCEPT:
A. the formation of reactive oxygen species
B. defects in plasma membrane permeability
C. increased permeability of mitochondrial membranes
D. calcium binding to endoplasmic reticulum
E. interference with oxidative phosphorylation

A

D

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22
Q 
Which of the following leak into the cytoplasm with mitochondrial damage?
A.  pyruvic acid
B.  phospholipases
C.  cytochrome C
D.  citric acid
E.  coenzyme A
A

C

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23
Q

Identify the correct sequence of events in hypoxic/ischemic cell injury:

  1. reduced activity of the plasma membrane Na+ pump
  2. decrease in oxidative phosphorylation
  3. influx of Na+, Ca2+, and water
  4. decreased ATP
  5. cell swelling
A.  2,1,4,3,5    
B.  4,1,2,3,5
C.  4,2,1,3,5
D.  2,4,1,3,5  
E.  1,3,2,4,5
A

D

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24
Q

All of the following occur in reversible hypoxic/ischemic injury EXCEPT:

A.  swelling of endoplasmic reticulum 
B.  formation of myelin figures
C.  detachment of ribosomes
D.  clumping of nuclear chromatin
E.  lysosomal membrane damage
A

E

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25
Q

Characteristics of hypoxic/ischemic cell injury include:

  1. mitochondrial swelling
  2. potassium influx
  3. an early fall in pH
  4. activation of acid hydrolases
  5. clumping of nuclear chromatin
A.  1,3,5
B.  1,2,5
C.  1,3,4,5
D.  1,2,4,5
E.  1,2,3,4,5
A

C

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26
Q

All of the following are true of free radical-induced cell injury EXCEPT:
A. Free radical damage of DNA involves reactions with thymine.
B. Reactive oxygen species can promote the mitochondrial permeability transition.
C. Reperfusion of ischemic tissues decreases the generation of free radicals.
D. Free radical formation can be induced by exogenous chemicals.
E. Oxygen free radicals attack the double bonds in the unsaturated fatty acids of membrane lipids.

A

C

27
Q 
Which of the following can catalyze free radical formation?
A.  nitric oxide
B.  iron
C.  vitamin E
D.  superoxide dismutase
E.  hydrogen peroxide
A

B

28
Q 
Free radical reactions are inactivated by all of the following EXCEPT:
A.  NADPH oxidase
B.  vitamin C		
C.  transferrin
D.  catalase
E.  glutathione peroxidase
A

A

29
Q

Which of the following promote apoptosis?

	1. Bcl-2
	2. granzyme B
	3. Bax
	4. NF-κB
	5. ceramide
	A.  1,2,5
	B.  2,3
	C.  2,4,5
	D.  1,3,5
	E.  2,3,5
A

E

30
Q 
Which of the following is a surface protein which marks apoptotic bodies for phagocytosis?
	A.  thrombospondin
	B.  transglutaminase
	C.  cytochrome C
	D.  granzyme B
	E.  endonuclease
A

A

31
Q 
Which of the following disrupts the binding between Apaf-1 and Bcl-2?
	A.  Bax
	B.  FAS
	C.  tranglutaminase
	D.  TNF
	E.  cytochrome c
A

E

32
Q

Which of the following is a light microscope feature of reversible cell injury?
A. distention and fragmentation of the endoplasmic reticulum
B. blunting and distortion of microvilli
C. small density formation in mitochondria
D. disaggregation of the polysomes from the endoplasmic reticulum
E. disaggregation of granular and fibrillar elements of the nucleus

A

A

33
Q

Which of the following are features of apoptosis?

	1. chromatin condensation and fragmentation
	2. cytoplasmic vacuolation
	3. cytoplasmic budding
	4. cell swelling
A.  1,2,3
B.  1,2,4
C.  1,3
D.  3,4
E.  2,4
A

C

34
Q

In which of the following scenarios do cells die predominantly by tissue necrosis?
A. occlusion of the pancreatic duct by a calculus
B. endometrial breakdown during menstruation
C. exposure to a lethal dose of radiation
D. resolving viral hepatitis
E. mild hypoxia

A

C

35
Q

All of the following are biochemical features of apoptosis EXCEPT:
A. caspase-mediated protein cleavage
B. transglutaminase-mediated protein cross-linkage
C. cytoplasmic endonuclease-mediated cleavage of DNA
D. lysosomal hydrolase-mediated loss of RNA
E. expression of phosphatidylserine on the cell surface

A

D

36
Q

Which of the following promote apoptosis?

	1. Bcl-XL
	2. Smac/DIABLO
	3. granzyme B
	4. Bad
	5. cytochrome c
	A.  1,3,5
	B.  2,4,5
	C.  1,2,5
	D.  2,3,4,5
	E.  4,5
A

D

37
Q

All of the following are true about Bcl-2 EXCEPT:
A. located on the outer mitochondrial membrane
B. can block the release of cytochrome c from mitochondria
C. protects cells from apoptosis by binding to cytochrome c
D. prevents activation of pro caspase 9
E. serves as a docking protein for Apaf-1

A

C

38
Q

Which of the following apoptotic regulators does NOT promote apoptosis?

	1. Bcl-2
	2. Bcl-XL
	3. Bax
	4. Bad
	A.  1
	B.  1 and 2
	C.  1 and 3
	D.  2 and 3
	E.  3 and 4
A

B

39
Q

All of the following are true about Apaf-1 EXCEPT:
A. It is activated by cytochrome c.
B. It directly activates an execution caspase.
C. It is sequestered by Bcl-2.
D. It sets in motion the proteolytic events that lead to apoptosis.
E. It binds to caspase 9.

A

B

40
Q

Match the following caspases with the appropriate function:

  1. caspase 9 a. initiation of apoptosis triggered by Fas-FasL interaction
  2. caspase 8 b. execution of apoptosis by activating CAD
  3. caspase 3 c. initiation of apoptosis triggered by cytochrome c release
  4. caspase 10 d. initiation of apoptosis triggered by granzyme B
	A.  1a, 2c, 3b, 4d
	B.  1a, 2c, 3d, 4b
	C.  1b, 2d, 3a, 4c
	D.  1c, 2a, 3b, 4d
	E.  1c, 2a, 3d, 4b
A

D

41
Q

DNA damage can stimulate apoptosis by which of the following mechanisms?
A. lack of transcription of Bcl-2 proteins
B. loss of normal p53 function
C. release of granzyme B
D. loss of caspase activity
E. upregulation of thrombospondin

A

B

42
Q 
Which of the following are enlarged in oncocytoma cells?
A.  lysosomes
B.  smooth endoplasmic reticulum
C.  ribosomes
D.  peroxisomes
E.  mitochondria
A

E

43
Q

Which of the following contribute to membrane damage in ischemic/hypoxic cell injury?

  1. loss of glycine
  2. acyl carnitine
  3. oxygen free radicals
  4. decreased cytosolic calcium
  5. proteases
	A.  1,2
	B.  1,2,3
	C.  1,3,4,5
	D.  1,2,3,5
	E.  3,5
A

D

44
Q 
Which of the following is a central factor in the pathogenesis of irreversible cell injury?
	A.  membrane damage
	B.  reduction in protein synthesis
	C.  cell swelling
	D.  reduction of intracellular pH
	E.  loss of the Na+/K+ pump
A

A

45
Q

Which of the following are antioxidant enzymes?

	1. glutathione peroxidase
	2. lipooxygenase
	3. catalase
	4. superoxide dismutase
	5. oxidase
	A.  1,2,3
	B.  1,3,5
	C.  1,3,4
	D.  1,2,3,4
	E.  1,2,3,4,5
A

C

46
Q

Which of the following molecules expressed on the surface of apoptotic bodies allow recognition by phagocytic cells?

	1. ICAM-1
	2. P selectin
	3. phosphatidylserine
	4. diacyl glycerol
	5. thrombospondin
	A.  1,2,4
	B.  3 only
	C.  3,4,5
	D.  1,3
	E.  3,5
A

E

47
Q

Inhibition of apoptosis by Bcl-XL involves which of the following?
A. binding of cytochrome c in the cytoplasm
B. prevention of cytochrome c release from mitochondria
C. binding of Apaf-1
D. stimulation of NF-κB
E. blocking of p53 expression

A

A

48
Q 
Which of the following protects cells from irreversible membrane injury?
A.  acyl carnitine
B.  superoxide
C.  glycine
D.  calcium
E.  lactate dehydrogenase
A

C

49
Q 
The apoptosome is composed of which of the following?
A.  Apaf-1 and Bcl-2
B.  Apaf-1 and Pro-caspase 9
C.  Cytochrome c and Bcl-2
D.  Cytochrome c and Apaf-1
	E.  Bcl-2 and Pro-caspase 9
A

D

50
Q 
All of the following are pro-apoptotic products of mitochondria EXCEPT:
A.  cytochrome c
B.  Bid
C.  endonuclease G
D.  SMAC/Diablo
E.  apoptosis-inducing factor
A

B

51
Q 
Caspase 3-induced DNA breakdown is the result of activation of which of the following?
A.  CAD
B.  NF-κB
C.  FLIP
D.  SMAC-Diablo
E.  Apaf-1
A

A

52
Q

Which of the following act as antioxidants?

  1. superoxide dismutase
  2. vitamin A
  3. ferritin
  4. catalase
  5. ceruloplasmin
	A.  1,4
	B.  2,4,5
	C.  1,2,4
	D.  2,3,4,5
	E.  1,2,3,4,5
A

E

53
Q 
Inhibitors of apoptosis include all of the following EXCEPT:
A.  Bcl-XL
B.  FLIP
C.  IAP
D.  survivin
E.  SMAC-Diablo
A

E

54
Q 
Which of the following molecules provides a link between the death receptor and mitochondrial pathways of apoptosis?
A.  caspase 3
B.  Apaf-1
C.  Bid
D.  Bcl-2
E.  Bax
A

C

55
Q

H2O2 is generated by _________________________?

a. Conversion of H2O and O2 by catalases
b. Fenton reaction from ˙OH
c. Hydrolysis of H2O
d. Incomplete reduction of O2 during oxidative phosphorylation
e. Superoxide dismutase from O2-

A

e, Robbins and Cotran, 8th Edition, 2010, p. 20

56
Q

Which of the following properties is attributable to lipofuscin but not to ceroid?

a. Deleterious effect on the cell
b. Formation due to heterophagia
c. Intracellular accumulation
d. Slow accumulation rate
e. Staining with Sudan Black

A

d, Zachary & McGavin, 5th edition, 2012, p. 44

57
Q

CN- (cyanide) precludes ATP generation by inhibiting the function of which mitochondrial enzyme?

a. NADH dehydrogenase
b. Succinate dehydrogenase
c. Cytochrome c oxidase
d. Cytochrome a oxidase
e. Succinate-Q oxidoreductase

A

c, Robbins and Cotran. 8th ed. 2010. Section 2.1.8

58
Q

Which statement is FALSE?

a. BAX has three BCL2 homology domains and leads to activation of caspase 9.
b. BAK is a BH3 only protein and inhibits antiapoptotic BCL2 family members.
c. BAK is proapoptotic.
d. BAX increases permeability of mitochondrial membranes.
e. BIM, PUMA, and BID bind with high affinity of all prosurvival BCL2 family members.

A

b, Hotchkiss RS, Strasser A, McDunn JE, Swanson PE: Cell death. N Engl J Med. 2009 Oct 15; 361(16):1570-83

59
Q

In which of the following processes does autophagy NOT play a role?

a. Sublethal stress of cells
b. Suppression of tumor growth
c. Deletion of toxic misfolded proteins
d. Antigen presentation
e. Elimination of intracellular viruses

A

e, Hotchkiss RS, Strasser A, McDunn JE, Swanson PE: Cell death. N Engl J Med. 2009 Oct 15; 361(16):1570-83

60
Q

Which of the following factors is responsible for muscle atrophy seen with cachexia?

a. TNF
b. FGF
c. Endothelin-1
d. TGF-B
e. Insulin growth factor 1

A

a, Pathological basis of disease, 8th edition, Robbins, pg 9

61
Q

What is the most reactive oxygen-derived free radical?

a. ONOO-
b. OH
d. O2-
d. H2O2
e. HNO2

A

b, Robbins and Cotran, 8th Edition, 2010, p. 20

62
Q

What enzyme is responsible for the conversion of glucose-6-phosphate to fructose-6-phosphate?

a. Glucose-6-phosphatase
b. Phosphoglucoisomerase
c. Phosphofructokinase
d. Phosphoglucomutase
e. Branching enzyme

A

b, PBVD p. 55

63
Q

What protein mediates mitochondrial fission?

a. Pink1
b. Opa1
c. Nbr1
d. Drp1
e. Parkin

A

d, Mitochondrial Fission, Fusion, and Stress. 2012. Science 337:1062.

64
Q

In what location is amyloid commonly deposited in the liver?

a. Sinusoids
b. Space of disse
c. Portal triads
d. Both “a” and “b”
e. Both “b” and “c”

A

b, PBVD, p. 37

Cell Injury and Death (1 decks)

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