Cell Injury Flashcards
1
Q
what are the two kinds of cell injury
A
reversible and irreversible
2
Q
describe reversible cell injury
A
cells will adapt to the changes in environment and returns to normal once stimulus is removed
3
Q
describe irreversible cell injury
A
permanent and leads to cell death
4
Q
what does cell injury mean for the body
A
there will be disease
5
Q
what is cell stress
A
cell injury
6
Q
what impacts how the cell stress impacts the cell
A
dose intensity and the cell vulnerability - some cells are more sensitive to change than others
7
Q
what can cell adaptation involve
A
change in cell metabolism or change in cell structure
8
Q
what is the point of no return for cell injury
A
this is when reversible injury persists for a period of time and no matter how the cell tries to adapt there will be a point where the cell cannot exist in the new environment
9
Q
what can happen if cell injury is irreversible
A
cell death
10
Q
what determines if injury will be reversible or irreversible
A
the type, duration and severity of the injury
the susceptibiilty and adaptability of the cell like nutritional status, metabolic needs and cardiac versus skeletal muscle
11
Q
what is the term used for the causes of cell injury
A
aetiology
12
Q
what are the causes of cell injury
A
hypoxia
physical agents
chemicals/drugs
infections
immunological reactions
nutritional imbalance
genetic defects
13
Q
what is hypoxia
A
decreased oxygen supply
14
Q
describe hypoxia and how it leads to cell death
A
this is oxygen deficiency and causes anaemia and respiratory failure
it disrupts the oxidative respiratory processes in cells to decrease ATP production
however cells can release energy via anaerobic mechanisms but is this limited
15
Q
what happens to cells when there is hypoxia
A
their supply of energy is greatly diminished
16
Q
what is ischaemia
A
the reduction in blood supply to tissues and is caused by blockage of arterial supply or venous drainage like atherosclerosis
it means there is a decrease in oxygen and nutrient supply to the tissue like glucose
17
Q
is ischaemia or hypoxia worse for cells
A
ischaemia as it is more severe and rapid to damage the cells than hypoxia and the anaerobic energy release will also be stopped
18
Q
what are some physical agents
A
heat electricity and radiation
19
Q
describe how mechanical trauma impacts cells
A
it affects their structure and cell membranes
20
Q
describe how extremes of temperature affect cells
A
they affect proteins and chemical reactions
21
Q
how does ionising radiation impact cells
A
damages DNA
22
Q
how does electric shock affect cells
A
it burns them
23
Q
is the damage from radiation immediately apparent
A
no the damage can occur years down the line from the exposure
24
Q
what is the common form of ulceration
A
traumatic ulcer of the lip
25
what are some infectious agents that can injure cells
bacteria
viruses
fungi
parasites
prions
26
do infectious agents damage cells through the same basic pathway
no they have a variety of different mechanisms that bring about the damage
27
what is an example of a simple host chemical that can cause damage to the body
glucose - when in excess it can affect many different organ systems
28
what is a poison that injures cells
cyanide blocks oxidative phosphorylation
29
what are occupational hazards that can injure cells
asbestos can cause inflammation
30
what do chemicals and drugs to do damage cells
they disrupt cell membranes and proteins
31
how does glucose cause damage in excess
it leads to osmotic disturbances
32
what are some immunological reactions that can damage cells
anaphylaxis
auto immunity
inflammation
33
summarise anaphylaxis
closure of airways due to type 1 hypersensitivity mediated by IgE immunoglobin
34
summarise how autoimmunity affects the cells in the body
type 2 hypersensitivity where antibodies are directed toward host antigens
type 3 hypersensitivity where there is formation of antigen antibody complexes can cause damage to cells
35
summarise inflammation and cell injury
inflammation from complement, clotting and the products of neutrophils can damage cells
36
what can too little nutrient intake lead to
either generalised deficiency or specific nutrient deficiency can affect the body
37
what is generalised nutrient deficiency associated with
anorexia
38
what is specific nutrient defiency associated with
scurvy and rickets
39
what can lead to excessive nutrient imbalance
hypervitaminosis where people are taking too much vitamin A or D
or obesity
40
what is HbS
sickled haemoglobin
41
describe how genetic defects can affect cells
there are some big changes in genetic makeup or more subtle changes that can lead to effects on cells - to do with DNA
42
give examples for genetic defects and their impacts on cell health
sickle cell anaemia can lead to clotting in blood vessels.
people with the trait develop sickling when exposied to low oxygen tension like whenunder general anaesthesia
inborn errors of metabolism can cause cell injury such as through the lack of an enzyme which can cuase build up of the enzyme substrate
43
what is disrupted in cells during reversible injury
- aerobic respiration and ATP synthesis due to mitochondrial damage
- plasma membrane integrity
- enzyme and structural protein synthesis
- DNA maintenance
44
what can the cells look like if there has been reversible injury
there can be cloudy swelling or fatty change
45
what leads to the cloudy swelling appearance of cells when there is reversible injury
the cells are incapable of maintaining ionic and fluid homeostasis whcih leads to failure of energy dependent ion pumps in the cell membrane
there is loss of ATP so the energy dependent sodium pump will influx sodium and water, which combined with build up of intracellular metabolites leads to swelling
46
is cloudy swelling an irreversible damage to cells
no it can be reversed
47
what does this image show
cloudy swelling in kidney tubules due to reversible cell injury
48
what causes the fatty change effect seen in some cells with reversible injury
accumulation of lipid vacuoles in the cytoplasm caused by the disruption of fatty acid metabolism so that triglycerides cannot be released from the cell, especially in the liver.
49
in what type of reversible cell injury does fatty change occur
toxic and hypoxic injury like in alcohol abuse, diabetes and obesity.
50
what can the liver look like when the cells undergo fatty change due to alcohol abuse
can become enlarged and pale due to the accumulation of lipid droplets in the cells
51
what is the main cause of fatty change
alcohol abuse
52
what are some reversible changes that can happen to injured cells
- dilation of organelles
- ribosome disaggregation
- blebbing
53
what happens at the point of no return in cell injury
mitochondrial high amplitude swelling
mitochondrial matrix densities
violent blebbing
54
what are examples of irreversible changes that occur in the cell following the point of no return
- membrane rupture, dispersal of organelles
- breakdown of lysosomes
- activation of inflammatory response
55
what is blebbing
this is when bits of the cell breaks off from the cytoskeleton
56
why does cell necrosis lead to inflammation
because the cell will burst and release its constituents into the surrounding space which recruits immune cells like macrophages to arrive and remove them by phagocytosis
57
what occurs in necrosis and what is it
cell death that usually occurs due to pathology.
occurs when there is irreversible cell injury, and intracellular protein denaturation and lysosomal digestion of the cell
disrupted cell membrane leaks the cell contents to trigger an inflammatory response
58
when can histopathological changes occur after necrosis
not necessarily immediately, they could take some time to appear
59
why are lysosomes released during necrosis
to digest the cell
60
what are the three stages to nuclear changes in necrosis
- pyknosis
- karyorrhexis
- karyolysis
61
what is pyknosis
this is when the nucleus shrinks and the nucleus will stain darker here
62
what is karyorrhexis
this is when the nucleus breaks up and fragments are produced
63
what is karyolysis
this is when the blue staining DNA in the nucleus is digested by endonucleases and the blue staining fades away
64
what is the end result of the nuclear changes that occur during necrosis
loss of the blue staining nucleus, which is a useful sign to show that the cell is necrotic
65
what happens to the cytoplasm during necrosis
the cytoplasm appears paler and swollen, and becomes more pink due to an increase in eosphinophilicness, this occurs due to denaturation of both cytoplasmic structural proteins and enzymes
66
what happens to the colour of the cytoplasm during necrosis
becomes paler and more pink (eosinophilic)
67
what makes a dead cell obvious
lack of nucleus
68
what are the types of necrosis
- coagulative necrosis
- liquefactive necrosis
- caseous necrosis
- fibrinoid necrosis
69
describe coagualative necrosis
- no proteolysis of the dead cells due to denaturation of enzymes
- the architecture of tissues is preserved for some days, but there is no nucleus
- firm in texture
- cells are digested by lysosomes of leukocytes
70
why is the architecture of the tissue preserved for a few days during coagulative necrosis
this is because the enzymes are denatured so there isnt any proteolysis
71
what are the dark dots on histological imaging of coagulative necrotic tissue
inflammatory cells
72
what is an infarction
localised area of coagulative necrosis
73
describe liquefactive necrosis
this is when there is digestion of dead tissues which mean the tissue is in a liquid viscous state
caused by focal bacteria or fungal infections and leads to an abscess
the necrotic material is thick and pale yellow in colour
74
what is the necrotic material produced from liquefactive necrosis
pus
75
what is an abscess
an accumulation of pus
76
what does the necrosis of the CNS as a result of hypoxia usually manifest as
liquefactive necrosis
77
what is colliquative necrosis
this is the liquefactive necrosis that causes pus production
78
what makes up pus
a mixture of tissue and pathogens
79
describe caseous necrosis
this is mostly seen in tuberculosis infections and causes the tissue to have a friable white appearance resembling cheese
microscopically it appears as granuloma fragmented cells and granular debris surrounded by apoptosis
80
where is there granular debris in caseous necrosis
mass apoptosis
81
what makes up the lesion in caseous necrosis
masses of granulation tissue made up of chronic inflammatory cells and multinucleated giant cells and fibroblasts
82
what is the appearance of caseous necrotic material
firm and crumbly lesion that looks like cheese
83
what is gangrenous necrosis
- occurs when blood supply to a limb is restricted and it will undergo coagulative necrosis
- also used when a limb undergoes liquefactive due to extensive bacterial infection - degradative enzymes due to infection causes the "wet gangrene".
- two pathways linked to this name then
84
describe fat necrosis
this is when focal areas of fat are destroyed. the fat cells may be liquified by activated pancreatic enzymes like in acute pancreatitis
can laed to calcium salts being deposited within them
85
describe fibrinoid necrosis
this is a special type of necrosis seen in immune reactions in blood vessels
antibody antigen complexes are deposited in artery walls together with fibrin that leaks out of the vessels
bright pink and amorphous substances in H&E
86
what type of necrosis is often seen in blood vessels
fibrinoid necrosis
87
what are the effects of necrosis
- functional and it depends on the organ and tissue and how severe it was
- inflammation
- release of cell contents to activate inflammation which are then phagocytosed
- the necrotic areas is replaced by a scar and if the remains are not removed then calcium salts may be deposited in the necrotic tissue
88
when may calcium salts be deposited in necrotic tissue
if the cell remains are not removed by phagocytosis
89
what does a denatured cytoplasm indicate
coagulative necrosis caused from hypoxia and free radicals
90
what does a hydrolysed cytoplasm indicate
liquefaction necrosis caused by strong acids, snake venom, clostridia and neutrophils
91
what does mass apoptosis indicate
caseous necrosis from fungi or tuburculosis
92
what does saponified cytoplasm indicate
enzymatic fat necrosis by lipase
93
what does exposure to free radicals lead to
coagulation necrosis
94
what does acute pancreatitis lead to
enzymatic fat necrosis
95
what is apoptosis
this is genetically programmed cell death and orderly elimination of unwanted cells.
it can occur in pathological situations and requires energy.
there are distinct pathways involved but it does not cause inflammation
there is a different morphology compared to necrosis
96
does necrosis use energy
no
97
does apoptosis use energy
yes
98
what necrosis cause inflammation
yes
99
does apoptosis cause inflammation
no
100
what colour do cells stain as they undergo apoptosis
dark stain
101
what are some pathological triggers of apoptosis
- hypoxia or ischaemia
- viral infection
- dna damage
102
why does hypoxia/ischaemia lead to apoptosis
there is protein misfolding and the cell will undergo apoptosis
103
why does viral infection lead to apoptosis
cytotoxic t lymphocytes contain enzymes which can then induce apoptosis
104
why does dna damage cause apoptosis
p53 will activate caspases to trigger apoptosis
the cell contents are degraded by enzymes activated by the cell
105
what is p53
guardian of the genome
106
what are the physiological roles of apoptosis
- deletion of cell populations during embryogenesis
- hormone change dependent involution from the uterus breast and ovary
- cell deletion in proliferating cell populations to maintain the constant number of cells
- deletion of inflammatory cells after inflammation
- deletion of self reactive lymphocytes in the thymus
107
what does too much apoptosis lead to
degenerative diseases
108
what does too little apoptosis lead to
cancer
109
describe the morphology of apoptosis
- cell will shrink
- chromatin will condense to package the nucleus
- cell membrane remains intact with the formation of cytoplasmic blebs
- blebs break off to form apoptotic bodies
- cell phagocytosed by there is no widespread inflammation
110
why is there no inflammation in apoptosis
the fragments of the apoptotic cell are encased in the cell membrane and this does not cause inflammation this way
the cell is taken up by phagocytosis
111
describe the cell size in necrosis vs apoptosis
enlarged and swelling in necrosis
reduced from shrinkage in apoptosis
112
describe the nucleus in necrosis vs in apoptosis
in necrosis it undergoes pyknosis, karyorrhexis and karyolysis
in apoptosis there is fragmentation into nucleosome size fragments
113
describe the cell membrane in necrotic vs apoptotic cells
disrupted in necrotic, intact with altered lipid orientation in apoptotic
114
describe the cellular contents in necrotic vs apoptotic cells
enzymatic digestion that could leak out of the cell during necrosis, could be released in apoptotic bodies but otherwise intact in apoptosis
115
is there adjacent inflammation in necrosis or in apoptosis
frequently seen in necrosis
116
is the role of necrosis pathologic or physiologic
invariably pathologic due to a culmination of irreversible cell injury
117
is the role of apoptosis pathological or physiological
often it is physiological as a means of eliminating unwanted cells, but it may be pathologic after some forms of cell injury, especially DNA damage
118
what is intracellular accumulation
this is the accumulation of abnormal substances in cells
119
what are some forms of intracellular accumulation
- excessive normal cellular constituent
- abnormal endogenous / exogenous material
120
what are some normal cellular constitutents that can accumulate
water
lipids in fatty change
glycogen
121
what are some abnormal contents that can accumulate in cells
carbon
silica
metabolites
cholesterol
122
is accumulation in cells always permanent
no it can be temporary depending if it is cytoplasmic or nuclear
123
why does atherosclerosis occur
due to lipid deposition in the walls of blood vessels
cholesterol accumulation in macrophages and smooth muscle cells in blood vessel walls
124
where is cholesterol accumulation found
in atherosclerosis and at sites of haemorrhage and necrosis
125
why do macrophages get called foam cells at sites of cholesterol accumulation
they look like foam due to large size and pale colour, and when there are many packed together they look like foamy bubbles
126
why does cholesterol appear as empty spaces on stainings
it disappears when you prepare the slides
127
what is amyloid
a fibrillar protein material that is deposited as a result of pathologic processes
128
why is there a lot of amyloid found at sites of pathology
it is deposited as a result of pathologic processes to its production is increased when there is infection.
it is deposited in extracellular location mostly on the basement membrane, in various tissues and organs
the proteins can be produced by the body de novo or due to infection, inflammation or malignancy
129
where is amyloid often found in the body
the kidney heart liver and on the tongue
130
what are the types of amyloidosis
AL
AA
Abeta
AF
SSA
131
what is AL
primary amyloidosis, caused by disorder of the plasma cells produced too many immunoglobins.
amyloid light chain that is derived from light chain immunoglobins is the abnormal protein that will then deposit around organs
132
what is AA
asecondary amyloidosis, due to infection or inflammation. produces amyloid A which deposits.
myloid associated which is derived from proteins synthesised in the liver
133
what is Abeta amyloid associated with
alzheimers disease
134
what is the stimulus for amyloid deposition
chronic inflammation
multile myeloma
ageing
drug abuse
135
describe the histological appearance of amyloid
pink hyaline appearance that is difficult to identify with H&E so congo red staining is used instead
this is due to the beta pleated sheets in amyloid proteins, which stain pink or red depending on the staining used.
136
how can amyloid impact the kidney
affects the structure of the glomerulus and thickens the walls of the tubules which compromises the function of the kidney
137
describe pathological pigmentation
occurs due to a build up of pigmented substances in the cytoplasm
there is endogenous and exogenous pigmentation
138
describe endogenous pigmentation
occurs due to lipfuscin cellular lipid breakdown products such as:
- melanin
- haemosiderin localised bruising
- bilirubin
all appear brown
139
why are bruises different colours
due to the breakdown of red blood cells
140
when are melanocytes more active
when we are out in the sun
141
describe exogenous pathological pigmentation
carbon deposition is the most common
- in macrophages there is alveoli of the lungs
- black pigment suggests anthracosis
- inhaled soot or smoke
- can be severe in coal workers
142
what are other examples of exogenous pigmentation aside from carbon
tattoos
heavy metal salts like lead
pigmentation associated with intravascular drug use
143
what is pneumoconiosis
fibrosis in the lungs due to carbon build up
144
why is there pigmentation in people who inject recreational drugs
it is not sterile and often foreign objects can be injected alongside the drug
145
what are the two kinds of pathological calcification
dystrophic and metastatic
146
describe dystrophic calcification
this is when there are deposits of calcium phosphate in necrotic tissue
the levels of serum calcium are normal in this kind
147
what is an example of dystrophic calcification
valvular heart disease - calcification of valves
148
describe metastatic calcification
deposits of calcium salts in normal, vital tissue with raised serum calcium levels
often seen in connective tissues of blood vessels
can compromise the function of tissue
149
which type of calcification leads to increased calcium levels
metastatic
150
what can cause hypercalcaemia
- increased PTH due to a tumour in the gland
- destruction of bone tissue
- excessive vitamin D
- renal failure
151
what can cause destruction of bone tissue
leukemia
metastasis to bone
immobilisation
152
what is the cause of secondary hyperparathyroidism
renal failure
153
after how many days does the nucleus disapear from a cell when it is undergoing necrosis
1-2 days
154
what does the breakdown of lysosomes during necrosis lead to
- digestion of cells
- includes those produced from neutrophils in the inflammatory response
155
why does hypoxia cause apoptosis
leads to the formation of abnormal proteins due to misfolding
156
what happens in amyloidosis
the removal mechanism for abnormally formed proteins is impaired
amyloid proteins will build up on the organs and eventually damage them
157
where can lipofuscin be seen
surrounding the nucleus, seen in the liver and heart of ageing patients and patients with severe malnutrition or cachexia
158
how can intravascalar drug use cause pigmentation
- soot and foreign particles that enter the skin when the drug is cooked and enter via the needle
- post inflammaotry pigmentation around old needle sites
159
what is AF
familial amyloidosis that occurs due to inherited mutations causing mutated proteins being produced from the liver
160
what is SSA
senile systematic amyloidosis, deposits transthyretin protein which aggregates and deposits in the heart of older men
161
what is amyloidosis
deposition of abnormal proteins in the body that can go onto multiple organs and lead to organ failure
