Cellular response to stress Flashcards
1
Q
define pathology
A
the structural, biochemical and functional changes in cells, tissues and organs that underlie diseases
2
Q
what is the meaning of aetiology
A
the cause of the injury or disease
eg isit, genetic, infection or physical harm etc
3
Q
list some points in the checklist of potential aetiologies of injury or disease
A
- genetic (chromosomal anomaly)
- congenital (e.g. down’s syndrome)
- neoplastic (tumour)
- infective (eg virus)
- immune (eg arthritis)
- toxic (eg toxic reaction to medicine)
- vascular (eg hypertensive or diabetes)
- iatrogenic (clinician caused it, e.g. surgery gone bad)
- idiopathic (don’t know the aetiology)
- traumatic (e.g. blunt trauma)
4
Q
what is the etiologic agent
A
the causative agent
5
Q
how do you determine the pathogenesis
A
what is the sequence of events in the cells and tissues in response to the etiologic agent (causative agent) from the initial event to the final manifestation of the disease
6
Q
what can stress to normal cell homeostasis lead to
A
adaptation
7
Q
what can injurious stimulus to normal cell homeostasis lead to
A
cell injury
8
Q
what can also lead to cell injury
A
inability of adapted cell to adapt
9
Q
what can a mild transient of cell injury lead to
A
reversible injury
10
Q
give an example to mild transient to cell injury
A
minor burn which can heal
11
Q
what can severe, progressive cell injury lead to
A
irreversible injury
12
Q
give an example of a irreversible injury
A
broken bone to heal to the same extent
13
Q
what can irreversible injury lead to
A
cell death e.g.
- necrosis
or
- apoptosis
14
Q
give an example to adaptation
A
hyperplasia
15
Q
what is hyperplasia
A
increase number of cells due to adaptation to change
16
Q
name and give examples of hyperplasia
A
- physiological (eg puberty) vs pathological (eg virus-wart)
- hormonal hyperplasia at puberty
17
Q
give an example of a what hyperplasia can respond to
A
viral infections ie papillomavirus
18
Q
what is hypertrophy
A
increase in size of the cells, not the amount, in response to stress
19
Q
give an example of what hypertrophy will respond to
A
hypertension, causes heart cells to increase to pump more blood but can cause a heart attack/myocardial infarction
20
Q
what can happen when cells become too large to handle a large blood supply
A
tissue damage
21
Q
what is atrophy
A
decrease in cell size and number
22
Q
what types of atrophy are there
A
- physiological vs pathological
& - embryogenesis = physiological
23
Q
list things that can cause atrophy
A
- decreased workload
- deinervation
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation (lose hormones)
- pressure (tumour may obstruct blood supply to organ or tissue)
24
Q
what can an atrophy cause to the brain
A
- big sulci and giri become larger
25
what is metaplasia
stem cells differentiate to a different lineage i.e. columnar epithelium to squamous epithelium (which can handle more stress)
e.g. smoking changes lung cells
26
when is hypertrophy no longer useful
cell injury & cell death
27
quote what happens due to cell injury & cell death
injury occurs when cells are stressed so severely that they are no longer able to adapt or when cells are exposed to an intrinsically damaging agent (e.g. virus) or suffer from intrinsic (genetic change in cell or from smoking) abnormalities
28
list the causes of cell injury
- oxygen deprivation: (hypoxia) decreased blood low ischemia
- physical agents: hot/cold, trauma
- chemical agents/drugs: medication side effects
- infectious agents: bacteria, fungi, virus
- immunologic reactions: (autoimmune disease) SLE, RA
- genetic abnormalities: chromosome defect or an external agent e.g. smoking or UV
- nutritional imbalances: not enough calcium effects bones etc
29
describe the necrosis pathway
- normal cell
- damage
- irreversible injury
(e.g. sodium and potassium pump breaks down) causes swelling to the cell
myelin figure (breakdown of cell wall & nuclear membrane & lipid rafts formed)
swelling of endoplasmic reticulum and mitochondria (no water balance)
membrane blebs
& can lead to
- progressive injury to cell which can cause
breakdown of plasma membrane, organelles and nucleus
which results in leakage of contents of cell, organelles spill out and become degraded
- cell inflammation causes the presence of neutrophils associated with necrosis
30
what is always a result from pathologic insult
necrosis
31
list the steps that lead to necrosis
- cell swelling (can't maintain cell volume)
- plasma membrane blebs initially
- myelin figures - derived from damaged cell membrane and damaged cells nearby e.g. from lysosomes which attracts neutrophils and macrophages to clean up the area of necrosis
- nucelus damage DNA fragmentation
- breakdown of cell membrane
- leakage of cellular constituents - lysozymes, proteins, enzymes
- attract neutrophils/macrophages
32
list the patterns of tissue necrosis
- coagulative
- liquefactive
- gangrenous
- caseous
- fat
- fibrinoid
33
describe an example of coagulative necrosis
ischemia of kidney results in coagulative necrosis where this injury results in denaturing of proteins and enzymes, the tissue remains firm and structurally intact for several days
34
what does the area of necrotic change look like in coagulative necrosis
hard and firm
35
which types of organs does coagulative necrosis happen to
firm organs such as
| liver, spleen and heart
36
describe how liquefactive necrosis occurs
in contrast to coagulative necrosis, the cellular enzymes liquify the tissue resulting in a liquid/viscous mass also know as pus
37
what tissue does liquefactive necrosis occur on and on which type of tissue
central nervous system
| breakdown of the soft tissue in the CNS from infarcts
38
what does gangrenous necrosis usually describe the necrosis of
peripheral limbs following ischemia
39
which type of people is gangrenous necrosis seen in
diabetics (if not controlled, which leads to peripheral vascular nervous system)
40
what does gangrenous necrosis have a similar pattern to
coagulative necrosis
41
what is gangrene feet a mixture of
apoptosis and necrosis
42
describe caseous necrosis
necrosis surrounded by an inflammatory cell border, giving rise to a granuloma
43
which patients typically have caseous necrosis
TB patients
44
what resemblance does caseous necrosis have
cheese like
45
describe where caseous necrosis occurs, which causes TB
an infection at the apex of the lungs which is furthest away from oxygen
a sharp border of granular tissue (scarring) forms which protects the rest of the lungs from infection
46
what is fat necrosis associated with and how does it happen
associated with the pancreas
| with pancreatic lipases that then liquefy cells in the abdomen
47
what is fatty necrosis the accumulation of
calcium deposits with lipids
48
what are fibrinoid necrosis associated with and how does it occur
associated with blood vessels (blood constriction o vessels)
| where immune complexes (antibodies & antigens) attach to fibrin that has leaked from arterial walls
49
what is fibrinoid necrosis seen in
nephritis with SLE
50
give an example of fibrinoid necrosis
lupus, is a systemic disease
it gets autoimmune complexes, binding to the endothelial cells in the blood vessels, initiating a wound healing reaction which creates fibrosis of collagen fibres which results in restriction of the vessels aka fibrinoid
51
what occurs from the mechanism of cell injury
depletion of ATP (from decrease of oxygen supply) by 5-10% is trouble
52
what is the mechanism of depletion of ATP associated with
chemical or hypoxia stress (depletion of oxygen)
| eg in diabetes, hypertension, glaucoma and ARMD
53
list the mechanism of cell injury
1. decrease activity of NaKaTPase pump (sodium potassium)
2. glycolysis - anaerobic - lactic acid (increase = more acid)
3. CaATPase pump falls (calcium pump which pumps calcium out of the cell)
4. structural proteins not synthesised/loss of ribosomes
5. protein misfolding (can't undergo cell replication/protein synthesis)
6. mitochondrial and lysosomal membranes damaged and cell passes to necrosis (cell becomes injured and theres a risk of death, so proteins are misfolding, mitochondria is dislodged & lysosomes breakdown)
54
list the effect that damage to the mitochondrion by ischemia has
- decreased oxidative phosphorylation which leads to
- decreased ATP which leads to
- decreased sodium pump (so pumps the sodium out), increased anaerobic glycolysis (increase in glycogen reduced from decreased ATP and oxygen) and a detachment of ribosomes
- the decrease in the sodium pump leads to, an influx of calcium (as calcium pump breaks), water and intracellular sodium, which leads to
- swelling of endoplasmic reticulum, cellular swelling and loss of microvilli blebs (breakdown of cell membrane)
- an increase of anaerobic glycolysis lead to, decreased glycogen, increased lactic acid and decreased pH
- the decrease of pH leads to clumping of nuclear chromatin so the DNA becomes denatured
- the detachment of ribosomes leads to decreased protein synthesis as ATP prevents the attachment to the endoplasmic reticulum
- the decrease in protein synthesis leads to, increased lipid deposition so the lipids become clumped and broken down as there is no structural cytoskeleton
55
what happens when the calcium ATPase pump breaks down
there is an influx of calcium
56
what are high levels of intracellular calcium to the cell
toxic
57
what do high levels of calcium activate
a lot of enzymes and increased mitochondrial transition
58
what is calcium normally stored in
the endoplasmic reticulum and mitochondria
59
what happens when theres a excess of intracellular calcium
further cell damage occurs
60
what do the activation of cellular enzymes lead to
- phospholipase
- protease
- endo-nuclease
- ATPase
61
what does phospholipase do
breaks down the cell
62
what does protease do
breaks down protons
63
what does end-nuclease do
breaks down DNA
64
what happens to the ATPase with the activation of cellular enzymes
will be deactivated
65
what does phospholipase lead to
a decrease of phospholipids
66
what does a decrease od phospholipids lead to
membrane damage
67
what does protease lead to
disruption of membrane and cytoskeletal proteins
68
what does disruption of membrane and cytoskeletal proteins lead to
membrane damage
69
what does end-nuclease lead to
nuclear damage
70
what does the deactivated ATPase lead to
increased mitochondrial permeability transition
71
describe reactive oxygen species ROC
free radicals ROC are oxygen species with a single unpaired electron in a outer orbit
72
what do free radicals ROC damage
phospholipids
proteins
carbohydrates
nucleic acids
73
what do free radical ROC electrons do
find other electrons in cells to pair up with e.g. can go into the nucleus of a lipid cell to grab an electron which destroys everything in the process
74
cells usually have a low level of ROS, but what is the reason for its increase
owing to stress, the imbalance is high then so called 'oxidative stress' occurs and cell damage/necrosis ensues
75
what can blue light reaching the macula cause
damage to the retina & free radicals causing ARMD
76
what is the formation of ARMD the accumulation of
reactive oxygen species
77
what does incomplete reduction of oxygen and inflammation, radiation, chemicals, reperfusion, injury lead to in a mitochondria cell which generates reactive oxygen species
Superoxide -an anion which has a lone electron, is an enzyme called superoxdimutase which converts the superoxide anion into hydrogen peroxide (which is toxic) which undresses the fenton reaction with the iron catalyst which produced hydroxyl free radical electron which can pair up with an amino acid, lipid, anything
78
list the pathological effects in steps of ROS cell injury and death when ROS reacts with fatty acids
- oxidation leads to
- generation of lipid peroxidases leads to
- disruption of plasma membrane organelles
79
list the pathological effects in steps of ROS cell injury and death when ROS reacts with proteins
- oxidation leads to
| - loss of enzymatic activity, abnormal folding
80
list the pathological effects in steps of ROS cell injury and death when ROS reacts with DNA
- oxidation leads to
| - mutations, breaks
81
how does removal of free radicals via the antioxidant methods work
the SOD (super oxide) in the mitochondria converts oxygen into hydrogen peroxide (h202)
- glutathione peroxidase (in mitochondria) converts the hydroxyl anion into hydrogen peroxide into water and oxygen
- catalase (in peroxisomes) converts hydrogen peroxide into water and oxygen
82
what is apoptosis
programmed cell death
83
how does apoptosis occur
- specific enzymes degrade their own nuclear DNA which initiates cell death
84
what is the condition of the cell membrane of an apoptotic cell
it remains intact
| even though it breaks down into small apoptitic bodies, we don't get spewing out of the entire cell content
85
what are apoptitic cells phagocytosed by
macrophages
eg osteoclasts within bones
microglial within retina
86
how does apoptosis in pathologic conditions occur with DNA damage
radiation triggers cell death e.g. high exposure to radiation
87
how does apoptosis in pathologic conditions occur with accumulation of misfolded proteins owing to genetic mutation trigger
triggers cell death
| can be inherited or from trauma e.g. UV or radiation
88
how does apoptosis in pathologic conditions occur with viral infections
trigger cell death to prevent further spread of virus (altruism)
so the tissue remains healthy but the viral cell becomes apoptitic to prevent spread
89
what are the two methods of apoptosis
intrinsic
| & extrinsic
90
how does the intrinsic method of apoptosis occur
mitochondria damage
release of cytochrome-c
initiates caspases (enzyme which breaks down nucleic acids into fragments)
cell death by endonucleases cleaving DNA
91
what are caspases
enzyme which breaks down nucleic acids into fragments
92
how does the extrinsic method of apoptosis occur
expression of Fas and TNF receptors recognised by T-cells
| that then induce apoptosis via caspases and endonucleases
93
which method of apoptosis is less common
extrinsic
