Session 1-Cell Injury Flashcards

1
Q

What does the degree of injury depend on?

A

Type of injury
Severity of injury
Type of tissue

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2
Q

What kind of things can cause cell injury?

A
  • Hypoxia
  • Toxins
  • Physical agents
  • Radiation
  • Microorganisms
  • Immune mechanisms
  • Dietary insufficiency and deficiencies, dietary excess
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3
Q

What is the difference between hypoxia and ischaemia?

A

Hypoxia=decreased O2 supply

Ischaemia=decreased blood supply

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4
Q

What is hypoxaemic hypoxia?

A

Arterial content of O2 is low

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5
Q

What is anaemic hypoxia?

A

Decreased ability of haemoglobin to carry O2

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6
Q

What is ischaemic hypoxia?

A

Interruption to blood supply

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7
Q

What is histiocytic hypoxia?

A

Inability to utilise O2 in cells due to disabled oxidative phosphorylation enzymes

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8
Q

How does the immune system damage the body’s cells? (2)

A

1) Hypersensitivity reactions-host tissue is injured secondary to overly vigorous immune reaction
2) Autoimmune reactions-immune system fails to distinguish self from non-self

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9
Q

What is an example of a hypersensitivity reaction?

A

Urticaria=hives

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10
Q

What is an example of an autoimmune reaction?

A

Grave’s disease of thyroid

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11
Q

Which cell components are most susceptible to injury? (4)

A

1) Cell membranes
2) Nucleus
3) Proteins
4) Mitochondria

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12
Q

In hypoxia, what is happening at a molecular level to the Na/K pump?

A

Stops working so influx of Ca2+, water and Na+ and an efflux of K+ and this can lead to swelling, blebs, ER swelling

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13
Q

Why do ribosomes detach from RER in hypoxia?

A

Ribosomes are attached to RER using energy from ATP, hypoxia leads to less ATP so ribosomes detach and there is less protein synthesis

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14
Q

What can prolonged hypoxia lead to?

A

Increased cytosolic Ca2+ and consequent activation of ATPase, phospholipase, protease and endonuclease

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15
Q

True or false: prolonged hypoxia is reversible

A

FALSE - irreversible

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16
Q

What are free radicals?

A

Reactive oxygen species with a single unpaired electron in an outer orbit-unstable configuration so can react with other molecules, producing more free radicals

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17
Q

What are the three free radicals of particular biological significance in cells?

A

OH (big dot) - hydroxyl, most dangerous
O2- (superoxide)
H2O2

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18
Q

How are free radicals produced? (5)

A

1) normal metabolic reactions
2) inflammation
3) radiation
4) contact with unbound metals within body: iron and copper
5) drugs and chemicals

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19
Q

How does the body control free radicals? (3)

A

1) Anti-oxidant system (donate electrons to free radical)
2) metal carrier and storage proteins sequester iron and copper
3) enzymes neutralise free radicals

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20
Q

Give two examples of metal carrier and storage proteins used to control free radicals

A

Transferrin

Ceruloplasmin

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21
Q

What is it called if the number of free radicals overwhelms the anti-oxidant system?

A

Oxidative imbalance

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22
Q

What is the main target of free radicals and what does this cause?

A

Lipids in cell membranes

Cause lipid peroxidation, leading to autocatalytic chain reaction

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23
Q

What other molecules can free radicals oxidise?

A

Proteins, carbs and DNA-bend out of shape, break or become cross-linked

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24
Q

Which type of proteins can be used to protect the cell against injury?

A

Heat shock proteins - mend mis-folded proteins and maintain cell viability

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25
Q

What do injured cells look like under a microscope in hypoxia?

A

Pale and swollen

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26
Q

What does a dead cell look like under a microscope in pyknosis?

A

Very pink as proteins denature and coagulate

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27
Q

What does a cell look like under a microscope in karyorrhexis?

A

Nucleus breaks into pieces

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28
Q

What is a characteristic of a karyolytic cell?

A

No nucleus

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29
Q

What are blebs?

A

Cytoskeleton is broken down by proteases, the membrane is looser and not held in place

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30
Q

How can cell death be diagnosed?

A

By testing its function-add dye/fluorescence and if the membrane is defected, the dye will enter. Only dead cells will look coloured

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31
Q

Define oncosis

A

Cell death with swelling, changes that occur in injured cells prior to death

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32
Q

What is necrosis?

A

Morphologic changes that occur after a cell has been dead some time (12-24 hours)

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33
Q

What are the two main types of necrosis?

A

Coagulative

Liquefactive (colliquitive)

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34
Q

What are the two other special types of necrosis?

A

Caseous

Fat necrosis

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35
Q

What happens in coagulative necrosis?

A

Ischaemia of solid organs in which proteins denature and become clotted and clump together

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36
Q

Give an example of an organ that may suffer from coagulative necrosis

A

Kidney

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37
Q

What is a solid organ?

A

Organ with lots of CT support

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38
Q

What happens in liquefactive necrosis?

A

Ischaemia in loose tissues, presence of many neutrophils and enzymes are released

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39
Q

Give an example of an organ likely to suffer from liquefactive necrosis

A

Brain

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40
Q

What does coagulative necrosis look like?

A

Cellular architecture is preserved and the cells have a “ghost outline”

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41
Q

What does liquefactive necrosis look like?

A

Enzymatic digestion of tissues

42
Q

What is caseous necrosis?

A

Contains amorphous (structureless) debris

43
Q

What is caseous necrosis commonly associated with?

A

Tuberculosis

44
Q

What does caseous necrosis look like?

A

Cottage cheese ew

45
Q

Define gangrene

A

Necrosis visible to the naked eye

46
Q

Define infarction

A

Necrosis caused by reduction in arterial blood flow, can result in gangrene

47
Q

Define infarct

A

Area of necrotic tissue which is the result of loss of arterial blood supply

48
Q

What is dry gangrene?

A

Necrosis modified by exposure to air (coagulative necrosis)

49
Q

What is wet gangrene?

A

Necrosis modified by infection (liquefactive necrosis)

50
Q

What is gas gangrene?

A

Wet gangrene where infection is with anaerobic bacteria that produce gas

51
Q

What are the commonest causes of infarction? (2)

A

Thrombosis

Embolism

52
Q

Why are some infarcts white?

A

In solid organs when the end artery is occluded so there is no blood supply

53
Q

Why are some infarcts red?

A

Infarct complicated by haemorrhage - mainly in loose tissue with dual blood supply

54
Q

What do the consequences of infarction depend on?

A

Alternative blood supply
Speed of ischaemia
Tissue involved
O2 content of blood

55
Q

What is ischaemia-reperfusion injury?

A

If blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than if blood flow hadn’t been returned

56
Q

What can cause ischaemia-reperfusion injury?

A

1) increased production of oxygen free radicals with reoxygenation
2) increased number of neutrophils resulting in more inflammation
3) delivery of complement proteins and activation of complement pathway

57
Q

True or false: when membranes are leaky, molecules can leak out as well as in

A

TRUE

58
Q

Which important things can leak out of membranes? (3)

A

1) potassium-can lead to cardiac arrest
2) enzymes
3) myoglobin-blocks glomerulae in kidney and can cause renal failure

59
Q

What is rhabdomyolysis?

A

Lots of skeletal muscle breakdown

60
Q

What is apoptosis?

A

Cell death with shrinkage

61
Q

True or false: apoptosis is the equal and opposite force to mitosis

A

TRUE

62
Q

True or false: lysosomal enzymes are involved in apoptosis

A

FALSE

63
Q

When does apoptosis occur physiologically?

A

In order to maintain steady state
Hormone-controlled involution
Embryogenesis

64
Q

When does apoptosis occur pathologically? (3)

A

1) Cytotoxic T cell killing of virus-infected or neoplastic cells
2) When cells are damaged, particularly with damaged DNA
3) Graft vs host disease

65
Q

What is graft vs host disease?

A

Occurs after bone marrow transplant for leukaemia-sometimes new WBCs recognise the host as foreign therefore graft vs host disease

66
Q

What is budding in apoptosis?

A

Contains parts of organelles and become apoptotic bodies

67
Q

What are the three phases of apoptosis?

A

1) Initiation
2) Execution
3) Degradation and phagocytosis

68
Q

Which two mechanisms trigger initiation and execution of apoptosis and what do both of these result in?

A

Intrinsic and extrinsic

Result in activation of caspases

69
Q

What are caspases?

A

Enzymes that control and mediate apoptosis and cause the cleavage of DNA and proteins of cytoskeleton

70
Q

How is the intrinsic pathway of apoptosis initiated?

A

Triggered most commonly be irreparable DNA damage and withdrawal of growth factors or hormones

71
Q

How is the intrinsic pathway of apoptosis carried out?

A

P53 protein is activated, resulting in outer mitochondrial membrane becoming leaky. Cytochrome C is released from mitochondria and this causes activation of caspases

72
Q

How is the extrinsic pathway of apoptosis initiated?

A

Triggered by cells that are a danger eg. Tumour cells, virus-infected cells

73
Q

How is the extrinsic pathway of apoptosis carried out?

A

One of the signals is TNF-alpha, secreted by T killer cells. This binds to cell membrane receptor (“death receptor”), resulting in activation of caspases

74
Q

Why are apoptotic bodies phagocytosed?

A

Express proteins on their surface which are recognised by phagocytes or neighbouring cells and degradation takes place

75
Q

True or false: the plasma membrane is intact in apoptosis

A

TRUE

76
Q

Where do abnormal cellular accumulations come from? (3)

A

1) Cell’s own metabolism
2) Extracellular space
3) Outer environment

77
Q

What kind of things can accumulate in cells?

A
  • water and electrolytes
  • lipids
  • carbs
  • proteins
  • ‘pigments’
78
Q

When does fluid accumulate in cells?

A

Hydropic swelling when energy supplies are cut off (hypoxia), Na+ and water flood into cells

79
Q

Where is hydropic swelling a particular problem?

A

Brain-compresses and pressure in the skull increases

80
Q

When do lipids accumulate in cells?

A

Steatosis (accumulation of triglycerides)

81
Q

Where is steatosis most common?

A

Liver

82
Q

What are the causes of lipid accumulation in cells? (4)

A

1) Alcohol
2) Diabetes mellitus
3) Obesity
4) Toxins

83
Q

Which is the only organ that can eliminate cholesterol?

A

Liver

84
Q

Complete the sentence:

Cholesterol accumulates in _______ muscle cells and macrophages in _______________ plaques called _____ cells.

A

Smooth
Atherosclerotic
Foam

85
Q

In which conditions do proteins accumulate in cells? (2)

A

1) Alcoholic liver disease (Mallory’s hyaline)

2) alpha-1-antitrypsin deficiency

86
Q

When do pigments accumulate in cells? (2)

A

1) carbon/coal dust/soot (air pollutant)

2) tattoos

87
Q

Give an example of an endogenous pigment

A

Haemosiderin (iron storage molecule)

88
Q

When does haemosiderin form?

A

Systemic or local excess of iron (eg bruise)

89
Q

What is the systemic overload of iron in organs called?

A

Haemosiderosis

90
Q

What is hereditary haemochromatosis?

A

Genetically inherited disorder resulting in increased intestinal absorption of dietary iron

91
Q

What are the symptoms of hereditary haemochromatosis? (3)

A

1) Liver damage
2) Heart dysfunction
3) Multiple endocrine failures, including pancreas

92
Q

What is the treatment for hereditary haemochromatosis?

A

Repeated bleeding

93
Q

What accumulates in jaundice?

A

Bilirubin (breakdown product of heme)

94
Q

What is localised calcification called?

A

Dystrophic

95
Q

What is generalised calcification called?

A

Metastatic

96
Q

True or false: metastatic calcification is more common than dystrophic

A

FALSE - other way round

97
Q

Why does metastatic calcification occur?

A

Hypercalcaemia secondary to disturbances in calcium metabolism

98
Q

What causes hypercalcaemia? (2)

A

1) increased secretion of parathyroid hormone (PTH) resulting in bone resorption
2) destruction of bone tissue

99
Q

Why can germ cells and stem cells continue to replicate?

A

Contain telomerase which maintains the length of telomeres

100
Q

Why can cancer cells replicate multiple times?

A

Produce telomerase