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Pathology > Cell Injury and Death > Flashcards

Cell Injury and Death Flashcards

1
Q

Cell response to injury is dependent on what four factors?

A

Dose
Duration
Type of injury
Type of cell

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2
Q

Cell injury results when what happens?

A

Cells are stressed so severely that they are no longer able to adapt

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3
Q

What types of cells are most affected by chemo?

A

Epithelial cells of the intestine, or any cells that replicate continuously

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4
Q

What are the three permanent cell types?

A

Skeletal muscles cells
Cardiac cells
Neurons

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5
Q

What are the two outcomes of irreversible injury to a cell?

A

Necrosis or apoptosis

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6
Q

What are the five main cellular components (processes/structures) that are damaged during cell injury?

A
  1. Aerobic respiration
  2. Integrity of cell membranes
  3. Protein synthesis
  4. Cytoskeleton
  5. Genetic apparatus
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7
Q

What are the three components of cell that undergo damage?

A

Membranes
Proteins
DNA

(MPD)

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8
Q

What are the five major biochemical mechanisms of cell injury?

A
  1. Ca influx into cell
  2. ROS accumulation
  3. ATP Depletio
  4. Mito damage
  5. Permeability of membrane changes

(CRAMP)

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9
Q

Are all free radicals bad?

A

No–we need them

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10
Q

Excess Ca causes what? (2)

A

Activation of enzymes

Changes permeability of Mitochondria, restricting ATP production

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11
Q

What are the four major enzymes that Ca influx activates?

A
  1. Phospholipases
  2. Proteases
  3. Endonucleases
  4. ATPase
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12
Q

What are the three major sources of Ca excess?

A
  1. ER stores
  2. Malfunction of Na/Ca pumps
  3. Extracellular Ca
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13
Q

What is the main organelle that is affected by Ca influx?

A

Mito

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14
Q

How is damage to the mito by Ca influx effected?

A

Breakdown of phospholipids (A2 and sphingomyelin) via enzymes activated by Ca. These lipids can be damaging

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15
Q

What happens when the Mitochondrial membrane is damaged?

A

Loss of H+ gradient, therefore loss of ATP

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16
Q

A decrease in oxygen affects the mitochondria how? (4)

A

Decrease ATP generation

ROS go up and leak out

Increase in proapoptotic proteins

Decrease in anti-apoptotic proteins

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17
Q

What is the effect of CN?

A

Inhibits the ETC, (cyt C) inhibiting ATP production

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18
Q

What happens when oxidative phosphorylation cannot proceed and ATP levels decrease? (3)

A

Na is not able to be pumped out, causing water influx and efflux of K

Anaerobic glycolysis (lactic acid)

Detachment of ribosomes (decreased protein synthesis)

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19
Q

What happens to the DNA when pH decreases?

A

Chromatin clumping (DNA damage)

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20
Q

What happens to out membranes with age? What is the consequence of this?

A

Leaky membranes, leaking ROS

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21
Q

True or false: normal metabolism leads to ROS production?

A

True

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22
Q

Why are ROS bad?

A

Bind to whatever double bond that’s around

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23
Q

What happens when someone is put on 100% O2?

A

ROS production

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24
Q

Reperfusion injury is caused by what?

A

ROS production increases but enzymes to take care of it are not around

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25
Q

Why do PMNs produce ROS?

A

Part of immune response

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26
Q

What are the four major ROS?

A

O2-
OH -
ONOO -
Lipid peroxide radicals

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27
Q

Where do ROS affect lipid membranes? What is produced?

A

The double bonds of FAs

This leads to peroxide formation, and continues

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28
Q

What are the vitamins that are antioxidants (4)?

A

C, E, A and beta-carotene

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29
Q

What happens to proteins with ROS? (2)

A

Side chain oxidation leads to change in structure (enzymes die)

Form disulfide bonds

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30
Q

Free radical interaction with thymine leads to what? What can this lead to?

A

Single-stranded breaks in DNA

CA

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31
Q

What is the function of superoxide dismutase?

A

O2 to H2O2

32
Q

What are the ROS enzymes that reduce free radicals? (3)

A

Superoxide dismutase
Glutathione peroxidase
Catalase

33
Q

What are the steps of the respiratory burst of PMNs? (hint there are three enzymatic steps)

A

O2 converted to superoxide by NADPH oxidase.

SOD to H2O2 packed in granules for release

Myeloperoxidase also packs HOCl and Oh radical

34
Q

What is chronic granulomatous disease?

A

The NADPH oxidase is malfunctioning

Pts die of infection early d/t granuloma infection

35
Q

Damage to membrane permeability causes what three damaging process?

A

Release and activation of phospholipases

Decreased phospholipid re-acylation

Cytoskeleton damage via protease activation

36
Q

What happens in reversible cell injury (4)?

A

Swelling of ER and mito,

Membrane blebs produced

Detachment of ribosomes from ER

Chromatin clumping

37
Q

What happens in irreversible cell injury (6)?

A
  1. Lysosome rupturing
  2. Nuclear condensation
  3. Myelin figures produced
  4. Ribosome loss d/t swollen ER
  5. Holes in the membrane
  6. Swollen mito
38
Q

What happens to renal tubules with reversible damage?

A

Raggedness, but nuclei are still intact

39
Q

What happens to renal tubules with IRReversible damage?

A

Nucleus breaks and dissolved

40
Q

Are renal tubule cells able to reproduce?

A

Yes

41
Q

Is there a particular point when reversible to irreversible injury occurs?

A

no

42
Q

What are the two forms of cell death?

A

Necrosis

Apoptosis

43
Q

True or false: apoptosis and necrosis are always pathologic

A

False–apoptosis can be physiologic, but true for necrosis

44
Q

What happens in necrosis that is so bad?

A

Leakage of cellular contents leading to inflammation

45
Q

What is necrosis?

A

Uncontrolled cell death that does not require signals or activation of genes

46
Q

What are the cytoplasmic changes with necrosis (3)?

A

Eosiniphilia
Glassy appearance
Vaculoation

47
Q

What are the three nuclear changes with necrosis?

A

Pyknosis
Karyorrhexis
Karyolysis

48
Q

Hypoxia can be the result of what factors?

A
  1. Loss of blood supply
  2. Decrease in oxygen carrying capacity of the blood
  3. Poisoning of the enzymes of the oxidative phosphorylation
49
Q

Chemical injury to a cell leads to what?

A

to a disruption of the physical structure of the cell or to a breakdown of the biochemical processes of the cell

50
Q

What is kwashiorkor?

A

inadequate protein intake

51
Q

What is marasmus?

A

inadequate calorie intake

52
Q

What are the six specific biochemical process seen in the process of cell necrosis? (what happens to ATP prodcution? Ca? ROS? Membrane permeability? Mitochondira? Cytoskeleton)?

A
  1. ATP depletion
  2. Loss of Ca
  3. Free radicals
  4. Defective membrane permeability
  5. mito damage
  6. Cytoskeletal damage
53
Q

What is oxidative stress?

A

The accumulation of damage caused by oxygen-derived free radicals

54
Q

What nucleic acid do free radicals react with to cause DNA damage?

A

Thymine

55
Q

What is the function of Glutathione peroxidase?

A

Converts OH- to H2O2

56
Q

What is the function of Superoxide dismutase?

A

Converts O2 radical to H2O2

57
Q

What are the three areas of the cell that are affected by free radicals?

A

Membrane (lipids/FA)
Proteins
DNA

58
Q

What are the changes seen in chronic cell injury?

A

Mito changes

Cytoskeletal changes

59
Q

What is Pyknosis?

A

Nuclear material becomes condensed

60
Q

What is Karyorrhexis?

A

Nuclear material breaks apart

61
Q

What is Karolysis?

A

Nuclei have totally dissolved

62
Q

How can aerobic respiration affected in cell injury?

A

Decreased ATP synthesis leads to lower Na/Ca pump activity, causing Ca influx

63
Q

How can a compromise in integrity of the cell membrane lead to cell injury?

A

Increase in Ca influx or ROS leakage from cells

64
Q

How can protein synthesis be affected in cell injury?

A

Either disulfide bonds are formed where there should be none, or there may be other changes in AAs

Also, ribosomes may fall off

65
Q

What cause the chromatin clumping seen in cell injury?

A

Lowered pH, caused by increase in glycolysis

66
Q

What happens to lysosomes during cell injury?

A

Can leak, causing severe damage to the cell

67
Q

What happens to the ER in cell injury?

A

Swells, possibly leading to ribosome detachment

68
Q

What happens to the mitochondria during cell injury? (4)

A
  1. Swelling
  2. loss of phospholipids reacylation/synthesis
  3. Decreased ATP
  4. Increased ROS
69
Q

What happens to the cytoskeleton during cell injury?

A

Broken down d/t increase protease activity from Ca influx

70
Q

What happen to the nucleus during cell injury?

A

fibrillar and granular components of the nucleolus may segregate

Can also undergo pyknosis

71
Q

What are the three mechanisms of reducing ROS in a normal cell?

A

Superoxide dismutase
Glutathione peroxidase
Catalase

72
Q

What is the reaction catalyzed by superoxide dismutase?

A

O2- to hydrogen peroxide

73
Q

What is the reaction catalyzed by glutathione peroxidase?

A

OH radical to hydrogen peroxide

74
Q

What is the reaction catalyzed by catalase?

A

Hydrogen peroxide to water and oxygen

75
Q

When ROS react with lipids, what do they form? What is the consequence of this?

A

Peroxides, causes chain reaction

76
Q

What are the four major changes that a loss of ATP leads to?

A
  1. Cellular organelle swelling
  2. Activated enzymes
  3. Chromatin clumping
  4. Decreased protein synthesis

Pathology (32 decks)

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