Cell Injury and Death Flashcards
1
Q
What are the 4 aspects of disease?
A
- Aetiology
- Pathogenesis
- Molecular and morphological changes
- Functional derangements and clinical manifestations
2
Q
What are the 2 main causes of disease?
A
- Genetic
- Acquired
3
Q
What 3 different genetic causes are there of disease?
A
- Inherited mutations
- Polymorphisms
- Disease associated gene variants
4
Q
What is pathogenesis?
A
The sequence of events of disease - cell response to aetiology
5
Q
What is the basic pathogenesis of cystic fibrosis?
A
Defective gene -> biochemical/morphological events -> formation of cysts etc.
6
Q
What are molecular and morphological changes?
A
Structural alterations
7
Q
What are functional derangements and clinical manifestations?
A
Signs
Symptoms
Progress
8
Q
Lethal and sub-lethal injury are another term for what?
A
Irreversible and reversible injury
9
Q
What causes of injury are there? Example of each
A
- Hypoxia e.g. myocardial ischaemia from coronary atherosclerosis
- Autoimmune e.g. thyroid gland damage from self-directed antibodies
- Infection e.g. bacterial/viral
- Genetic e.g. Duchenne muscular dystrophy
- Physical e.g. uv damage from sunburn
- Chemical e.g. acid damage
- Thermal e.g. excess heat or cold
10
Q
Mechanisms of injury for cell membrane damage
A
- cell mediated lysis
- bacterial toxins
- free radicals
11
Q
Mechanisms of injury for mitochondrial damage -> inadequate aerobic respiration
A
- hypoxia
- cyanide poisoning
12
Q
Mechanisms of injury for ribosome damage -> altered protein synthesis
A
- alcohol in liver cells - alcoholics
- antibiotics in bacteria - antibiotics interfere with ribosomes in bacteria
13
Q
Mechanisms of injury for nuclear damage
A
- viruses - damage nucleus
- radiation - DNA (single/double strand break) (point mutation
- free radicals
14
Q
What are free radicals?
A
Highly reactive unpaired electrons in outer orbit
15
Q
Where are free radicals produced and in response to what?
A
produced in cells in response to:
- radiation
- normal metabolic oxidative reactions
- drug metabolism
16
Q
What do the consequences of cell injury depend on?
A
- the cell
- injurious agent
- both
17
Q
what 3 cell features affect outcome of disease?
A
- specialisation of the cell
- cell state
- regenerative ability
18
Q
what aspects of the specialisation of the cell affect the outcome of disease?
A
- what enzymes the cell has
- specialised organelles
- the more specialised, the more vulnerable
19
Q
what aspects of cell state affect the outcome of disease?
A
- if it has adequate O2, hormones, nutrients, growth factors
- if not enough, more vulnerable
20
Q
what aspects of the regenerative ability of the cell affect the outcome of disease?
A
- damage to populations of permanent cells don’t regenerate
- e.g. head (neurones) can’t regenerate
- e.g. skin can replace
21
Q
what are liable cells?
A
constantly active self-renewal
22
Q
what are examples of liable cells?
A
gastrointestinal mucosa, skin, haematopoietic cells
23
Q
what are stable cells?
A
low level of renewal
24
Q
what are examples of stable cells?
A
liver, renal tubule cells, glial cells of CNS
25
what are permanent cells?
no capacity to replace cells
26
what are examples of permanent cells?
adult neurones, renal glomeruli, retinal epithelial cells
27
what 3 aspects of injury affect outcome of disease?
- type
- exposure type
- severity
28
how does the type of injury affect disease?
different types of injury e.g. ischaemic/toxic/chemical - different cells more susceptible to different types
i.e. heart muscle and ischaemia
29
how does injury exposure time affect disease?
toxin/lack of oxygen
30
how does injury severity affect disease?
hypoxia or anoxia = low or no O2
31
what 4 sites are important in cell injury/death?
mitochondria
plasma membrane
ion channels in cell membranes
cytoskeleton
32
reversible or irreversible? cell swelling
reversible
33
reversible or irreversible? mitochondrial swelling
reversible
34
reversible or irreversible? EPR swelling
reversible
35
reversible or irreversible? ribosomal detachment
reversible
36
reversible or irreversible? myelin figures
reversible
37
reversible or irreversible? loss of microvilli
reversible
38
reversible or irreversible? surface blebs
reversible
39
reversible or irreversible? chromatin clumping
reversible
40
reversible or irreversible? lipid deposition
reversible
41
reversible or irreversible? lysosomal enzyme release
irreversible
42
reversible or irreversible? protein digestion
irreversible
43
reversible or irreversible? loss of basophilia
irreversible
44
reversible or irreversible? membrane disruption
irreversible
45
reversible or irreversible? leakage of enzymes
irreversible
46
reversible or irreversible? pyknosis
irreversible
47
reversible or irreversible? karyorrhexis
irreversible
48
reversible or irreversible? karyolysis
irreversible
49
what is pyknosis?
nuclear shrinkage
50
what is karyolysis?
nuclear dissolution
51
what is karyorrhexis?
nuclear break up
52
what happens during lysozyme rupture?
break down what cell is made of (autodigest)
53
what is protein digestion?
enzyme and structural
54
what happens when the basophilia is lost?
cell less likely to stain with blue basic stain - more likely to stain with red acidic stain
55
how can you tell when someones had a heart attack?
measure cardiac cell enzymes in blood which will be released when cell is damaged
56
what 5 cellular adaptations to stress are there?
```
atrophy
hypertrophy
hyperplasia
metaplasia
dysplasia
```
57
what is atrophy?
cells get smaller
58
what is hypertrophy?
cells get bigger
59
what is hyperplasia?
increase in number of cells
60
what is metaplasia?
cells change appearance - thin and broad.
early cancerous changes
61
what is dysplasia?
cells disorganise
62
what is the mechanism of cell response to reversible injury?
1. transient ischaemia
2. less O2 to cells
3. less aerobic, more anaerobic
4. anaerobic increases cytoplasmic activity
5. ATP generation stops
6. plasma membrane pump swells
7. water is allowed in
8. chromatin clumps
9. pH change
63
what are the microscopic changes when cells are injured?
colour - red staining - more acidic
vacuolation - holes
clumping of chromatin
cells bigger/swollen
64
what is the mechanism of cell response to irreversible injury?
1. continued ischaemia
2. reversible changes
3. irreversible changes
4. cell membrane damage/rupture
5. calcium influx
calcium influx leads to:
- cessation of mitochonrial function (ATP production)
- digestive enzymes triggered (that are Ca2+ dependent), cell skeleton destroyed
= loss of vital cytoplasm/nuclear material
and lysosomal autodigestion triggered (due to membrane damage)
65
what happens if the mitochondria stops phosphorylation?
less ATP -> less Na pump ability
when Na/K pump stops working as well, water follows Na into cell = swelling
66
what causes an increase in phosphofructokinase?
decline in mitochondrial phosphorylation and decrease in ATP
67
what happens when phosphofructokinase increases?
1. increase in anaerobic glycolysis
2. increase in lactate
3. reduction in pH
4. clumping of nuclear chromatin
68
what happens when theres a decline in protein production?
polysomes detach from EPR
69
what happens during early ischaemic injury of kidney tubules?
surface blebs
eosinophilia
swollen cells
70
what happens during necrosis of kidney tubules?
fragmentation of cells
loss of nuclei
leakage of contents
71
what is autolysis?
processing of cell/tissue after you die by digestive enzymes (lysozymes)
72
what is apoptosis?
programmed cell death
73
how does apoptosis work?
Apoptotic cells remain viable and membrane pumps function until a terminal stage in the process
Cell shrinks
Nuclear chromatin condenses
Cell breaks up into apoptotic bodies
Macrophages or neighbouring cells phagocytose apoptotic bodies
Phagocytes recognise apoptotic cells by newly expressed membrane proteins
74
how is apoptosis initiated?
activation of genes for new proteins involved in apoptotic process e.g. endonuclease - causes DNA fragmentation
75
4 examples of physiological apoptosis
embryogenesis
menstrual cycle
breast feeding
immune cell development
76
3 examples of pathological apoptosis
tumours
atrophy
viral illness - e.g. hepatocytes during hepatitis
77
how does fas initiate apoptosis?
Binding of FAS ligand to FAS receptor
78
which cells express FAS ligand?
activated T cells
79
why do T cells express FAS?
to get rid of T cells over time to prevent accumulation of responsive immune cells/autoimmunity
80
what do cytotoxic T cells use FAS for?
use FAS with perforin to kill target cells
81
which cells with immune privilege express FAS ligand?
cornea, testis
82
why do the cornea and testis express FAS?
immune system doesnt recognise - so if immune system comes into contact then apoptose infiltrating lymphocytes
83
when is FAS turned off?
during pregnancy
84
what is tumour counter-attack?
over expression of FAS ligand by tumours to kill the cells that would kill the tumour
85
what is neoplasia?
formation of new, abnormal tissue
86
which oncogenes turn off apoptosis?
bcl-2
87
what are the microscopic changes of necrosis from irreversible injury?
```
Nuclear
pyknosis
karyorrhexis
karyolysis
Increased eosinophilia of cytoplasm
```
88
what are the ultrastructural changes of necrosis from irreversible injury?
high amplitude mitochondrial swelling
membrane defects
lysosomal membrane rupture
nuclear condensation, fragmentation, dissolution
89
what 5 types of necrosis are there?
1. coagulative
2. liquifactive
3. caseous
4. fat
5. gangrene
90
what is coagulative necrosis?
- firm tissue
- becomes denser
- looks paler/dry under microscope
- seen in infarction and ischaemia
- denied O2
- not so much trauma/toxins
91
what is liquifactive necrosis?
- liquid viscous mass from bacterial/fungal infections
- cell completely digested by hydrolytic enzymes
- soft area with pus/fluid
- dead leukocytes = creamy yellow pus
- associated with abscesses
- seen in the nervous system
92
what is caseous necrosis?
- cheese-like
- soft, white mass
- TB, syphillis, some fungi
93
what is fat necrosis?
- action upon fat by digestive enzymes
- lipase releases fatty acids from triglycerides and calcium = soaps
- white chalky deposits from calcium
- e.g. trauma of pancreas/acute pancreatitis
94
what is gangrene necrosis?
- ischaemia/infection
- thrombosis or clostridium perfringens
- risk with diabetes/smoking
- dry, wet or gas forms
95
what type of necrosis is a splenic infarction likely to be?
coagulative necrosis
96
what type of necrosis is a stroke likely to be?
liquifactive necrosis
97
what type of necrosis is a liver abscess likely to be?
liquifactive necrosis
98
what type of necrosis is TB likely to be?
caseous necrosis
99
what type of necrosis is intestine-thrombosis likely to be?
gangrene
100
what is the mechanism of calcium influx?
1. injurious agent
2. Ca2+ released from ER/other vacuoles
3. cytosolic Ca2+ levels increase
4. phospholipase, protease, ATPase and endonuclease released
phospholipase -> phospholipid
protease -> membrane cytoskeleton
ATPase -> reduce ATP
endonuclease -> chop chromosomes
101
what are the results of necrosis?
end of function
cellular enzyme release e.g. cardiac enzymes after MI
inflammatory response
102
how can you tell the difference between apoptosis/necrosis?
run DNA
