Lecture 2 - Cell Injury And Cell Death Flashcards

1
Q

What are the general cell responses to injury?

A

Cell adapts to the injury
Injured cell repairs if damage is reversible
Cell dies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens when the heart becomes damaged?

A

Myocytes have to work harder
Adaptation - Cardiac myocytes hypertrophy
Ventricular hypertrophy
More O2 for bigger cells needed
Hypoxia
Myocardial infarction/arrhythmia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 2 types of causes to cell injury?

A

Environmental
Non-environmental

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are some environmental causes of cell injury?

A

HYPOXIA
TOXINS
Immune mediated
Physical agents
Infection
Nutritional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are some non-environmental causes of cell injury?

A

Genetics
Ageing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is hypoxia?

A

Oxygen deprivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the 4 different causes of hypoxia

A

Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histiotoxic hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Hypoxaemic hypoxia?

A

Arterial content of oxygen is low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Anaemic hypoxia??

A

Haemoglobin has a reduced ability to carry oxygen (Anaemic or CO poisoning etc…)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Ischaemic hypoxia?

A

Interruption to blood supply

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Histiotoxic hypoxia?

A

Inability to utilise oxygen due to disabled oxidative phosphorylation enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What may be a cause of Histiotoxic hypoxia?

A

Cyanide poisoning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How quickly are neurones affected by hypoxia?

A

Affected after a few minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some immune mediated cases of hypoxia and what type of reactions are they?

A

Hypersensitivity reactions (anaphylaxis in allergy)

Autoimmune reactions (Graves disease of the thyroid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are hypersensitivity reactions?

A

Excessive immune response to non self antigens causing injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is an autoimmune reaction?

A

Immune system over reacts to a self antigens causing tissue damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do most mechanisms of cell injury lead to which causes damage?

A

Lack of ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the 2 main mechanisms of cell injury?

A

Depletion of ATP
Oxidative stress (free radicals)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 6 mechanisms of cell injury?

A

Depletion of ATP
Oxidative stress (free radicals)
Direct mitochondrial damage
Direct membrane damage
Disruption to calcium homeostasis
Direct damage to DNA and proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does Hypoxia result in ATP depletion?

A

Less O2
Less oxidative phosphorylation
Less ATP synthesised by mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the 3 ways reduced ATP affects the cell?

A

Affects pH
Calcium homeostasis of cells lost (calcium influx)
Protein synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does reduced ATP lead to pH being affected?

A

Increased anaerobic respiration
Increased lactic acid build up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does reduced ATP cause calcium influx into cells?

A

ATP sensitive Na+/K+ pumps affected
Na+ and water enter cell
Calcium also enters the cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does reduced cell ATP lead to protein synthesis being affected?

A

Ribosomes detach from ER
Reduced protein synthesis
Causes abnormal protein build up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does calcium influx cause irreversible cell damage?

A

Calcium activates enzymes like
ATPases
Phospholipases
Proteases
Endonucleases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Why is activation of phopholipases by excess calcium bad?

A

Breaks down membranes which can lead to cell contents leaking out

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the affect of activating proteases by excess calcium?

A

Cleaves proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the affect of activating endonucleases by excess calcium?

A

Breaks down DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Where are Free radicals generated?

A

The ETC
Ischaemic-repercussion injury
Cellular ageing
Antimicrobial killing by phagocytosis (respiratory burst)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are some examples of free radicals/ROS?

A

Hydroxyl
Superoxide O2-
Hydrogen peroxide H2O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the 3 ways which free radicals cause damage?

A

Lipids
Proteins
DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How do free radicals damage lipids?

A

LIPID PEROXIDATION
Unsaturated fatty acids get attacked producing more free radicals causing a chain reaction

Damages membranes causing calcium influx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How do free radicals damage proteins?

A

Causes cross linking (disulphide bonds)
Oxidation of protein is
Cleaving proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How do free radicals damage DNA?

A

Single or double stranded breaks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How do free radicals damage DNA?

A

Single or double stranded breaks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How does the body control number of free radicals?

A

Antioxidants
Transport proteins
Enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are some examples of antioxidants?

A

Vitamins C and E (Vit C regenerates reduced Vit E)
GSH
Abscorbic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What a re one transport proteins which help control free radicals?

A

Iron binds to transferrin
Copper binds to ceruloplasmin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is Wilsons disease?

A

Improper copper metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are some enzymes which control free radicals in the body?

A

Superoxide dismutase (SODs)
GSH peroxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the function of heat shock proteins?

A

Help deal with free radical damage
Help repair and refold damaged proteins or label them for degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are some indications that injured cells are reversibly injured?

A

Swelling
Clumped chromatin
Ribosome dispersion
Cytoplasmic blebs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are some indications that cells have been damaged irreversibly?

A

Membrane defects
Nuclear changes
Lysis of ER
Lysosome rupture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Why do cells swell?

A

Failure of Na/K+ pump

44
Q

Why does chromatin clump?

A

Reduced pH

45
Q

What is apoptosis?

A

Individual programmed cell death

46
Q

Is apoptosis pathological or physiological?

A

Can be both

47
Q

What does physiological mean?

A

Normal

48
Q

What happens to the size of cells in apoptosis?

A

Cells shrink
NO INFLAMMATION

49
Q

What are the enzymes which induce apoptosis?

A

Caspases

50
Q

What are the 2 pathways for apoptosis?

A

Intrinsic (mitochondrial)
Extrinsic (death receptor)

51
Q

How does intrinsic/mitochondrial apoptosis work?

A

Mitochondria release cytochrome C

Activates caspase enzymes

Caspase induces apoptosis

52
Q

How does extrinsic/death receptor apoptosis work?

A

Death receptor released by T killer cells

Death receptors bind to cell membrane activating caspase

53
Q

What is the Definiton of necrosis?

A

The morphological changes that occur after a cell has been dead some time (12-24hrs)

54
Q

What happens tot cell size in necrosis?

A

Cells swell

55
Q

What happens to the nuclei of cells in necrosis?

A

Pyknosis (shrinkage)
Karyorrhexis (fragmentation)
Karyolysis (dissolution)

56
Q

Is Necrosis Physiological or Pathological?

A

ALWAYS PATHOLOGICAL

57
Q

What are the different types of necrosis?

A

Coagulative (Main type)
Liquefactive (Main type)
Caseous
Fat necrosis
Fibrinoid

58
Q

What type of organs does coagulative necrosis affect?

A

Solid organs

59
Q

What is the definition of coagulative necrosis?

How does this appear histologically?

A

Proteins denature and coagulate

Retains ghost outline of cells and tissue architecture

60
Q

What tissue does liquefactive necrosis affect?
How is architecture affected?
Why does Liquefactive necrosis happen?

A

Loose tissue
COMPLETE LOSS OF ARCHITECTURE
Proteins broken down by enzymes

61
Q

What is Caseous necrosis and what does it indicate?

A

Seen in LUNG
Indicates TB
Cheese like

What type of giant cell is seen with this infection?
Langhans giant cell

62
Q

What is fat necrosis?

A

Direct trauma to fatty areas

63
Q

Compare how the DNA is cleaved in apoptosis Vs Necrosis:

A

Apoptosis = DNA cleaved neatly between nucleosomes

Necrosis = DNA randomly cleaved

64
Q

Is there inflammation in Necrosis?

A

Yes
None in Apoptosis

65
Q

What are the 3 important molecules released by injured cells which can be measured in the blood?

A

Potassium
Enzymes
Myoglobin

66
Q

Why excess potassium bad?

A

Cardiotoxic
Too much K+ stops the heart

67
Q

What cells relase K+?
When do cells release K+?

A

All cells when undergoing necrosis

68
Q

What enzymes are tested for in the liver function test?

What proteins are tested for in the liver function test?

A

AST/ALT
Aspartate Transaminase and Alanine Transaminase

Bilirubin and Albumin

69
Q

What enzymes are released into the blood following a myocardial infarction?

A

Troponin

Troponin I and Troponin T

70
Q

What enzymes are released into the blood in pancreatitis?

A

Amylase

71
Q

When is myoglobin released into the blood?

A

When skeletal muscle is damaged
Prolonged intense exercise

72
Q

Why is myoglobin in the blood a problem?

A

Myoglobin = TOXIC TO KIDNEYS

73
Q

What is characteristic of Rhabdomyolysis?

A

Dark brown tea coloured urine

74
Q

How do falls in the elderly lead to Rhabdomyolysis getting myoglobin into the blood?

A

Blood flow restricted on area that’s been fallen on
Ischaemic Hypoxia of skeletal muscle

75
Q

Why do Intracellular accumulations occur in cell injury?

A

Struggle to remove due to deranged metabolism

76
Q

What are the 3 types of accumulation?

A

Normal cel accumulations
Abnormal accumulations
Pigment

77
Q

Features of abnormal cellular accumulations:

A

Reversible or permanent
Harmful
Toxic

78
Q

Cerebral oedema is what type of accumulation?

A

Normal accumulation
Water

79
Q

What is cerbral oedema?

A

Hypoxia cell injury of neurones
Less ATP
ATP sensitive Na+ pump affected
Na+ enters cell with water
Brain swells

80
Q

Why is cerebral oedema so dangerous?

A

Brain is in skull so as it swells it has no where to go

81
Q

How does the brain get further damaged in cerebral oedema?

A

Brain compressed on skull
Blood supply cut out (Ischaemic hypoxia)
Liquefactive necrosis

82
Q

What is an example of an abnormal cell component accumulation?

A

Fatty liver disease
Liver cell injured
Fat accumulates

83
Q

What is Gangrene?

A

When necrosis is visible to the naked eye

BUT its NOT a type of necrosis

84
Q

What is an infarction?

A

Infarction is NOT a type of necrosis!! But it is a cause of necrosis

It causes necrosis by reduction in arterial blood flow/loss of blood suppply (ischaemic hypoxia normally the cause of necrosis)

Might be due to an embolism for example

85
Q

What is Ischaemia?

A

Inadequate blood supply to tissue

86
Q

What can Ischaemia cause?

A

Infarction
Which could in turn cause gangrene

87
Q

What are the 2 types of gangrene?

A

Dry and Wet

88
Q

What is Dry gangrene?

A

Necrotic area exposed to air

89
Q

What type of necrosis is dry gangrene?

A

Coagulative necrosis

90
Q

What is wet gangrene?

A

Necrosis caused by infection

91
Q

What type of necrosis causes wet gangrene?

A

Liquefactive necrosis

92
Q

Give some examples of dry gangrene and their appearance:

A

Gangrenous toes
Umbilical cord of new born (physiological)

Leaf like appearance

93
Q

What is gas gangrene and when does it usually happen?

A

Road traffic accidents (skin scrapped across dirty surface)

Infected with anaerobic bacteria

94
Q

What is a white infarct?

A

White in colour due to no haemorrhage

95
Q

What is a red infarct?

A

Red in colour due to haemorrhage

96
Q

Where do white infarcts usually happen?

A

Solid organs (spleen/kidney/heart)

Tissues loose blood flow

97
Q

Where do red infarcts usually happen?

A

In organs with a dual blood supply

98
Q

How does a red infarct happen?

A

Haemorrhaging into dead tissues usually from capillaries

99
Q

What is pathological calcification?

A

Abnormal deposition of calcium within tissues

100
Q

What is localised (dystrophic) pathological calcification?

A

Calcium migrates to dead tissues
Calcium metabolism s normal

101
Q

What is generalised (metastatic calcification?

A

Deposition in other wise normal tissue

Metabolic error causing high levels of circulating calcium

102
Q

How does excess alcohol cause liver disease?

A

Ethanol = toxin
Decreased NAD:NADH ratio
Increased fatty acid synthesis
Fat accumulates

103
Q

What is alcoholic hepatitis?

A

Florid inflammation of the liver

104
Q

What is released by hepatocytes in liver disease?

A

ALT and AST

105
Q

Once liver has undergone cirrhosis, is the damage reversible?

A

NO IRREVERSIBLY INJURED

106
Q

What are the complications of liver disease?

A

Bleeding
Encephalopathy
Ascites

107
Q

What is Encephalopathy?

A

Confusion due to toxins accumulating which would normally be removed by the liver

108
Q

Why does Ascites occur with liver disease?

A

Less protein synthesis in liver (less albumin) means plasma oncotic pressure is lower so less tissue fluid drawn back into blood