Cell injury Flashcards
1
Q
What are the 2 types of cell injury?
A
reversible and irreversible
2
Q
Definition of reversible cell injury
A
cell adapts to changes in environment in order to survive
3
Q
How is reversible injury resolved?
A
once the stimulus is removed, the cell returns to its normal shape and function
4
Q
Irreversible injury definition
A
a permanent change that results from an environmental change
5
Q
What is the consequence of irreversible cell injury?
A
cell death (apoptosis / necrosis)
6
Q
What leads to a cell injury progressing from reversible to irreversible?
A
the cell can no longer survive in the environment in its current state - passes the ‘point of no return’
7
Q
What factors determine whether an injury is reversible or irreversible?
A
Dose intensity (type, duration, severity of injury) and cell susceptibility/adaptability (nutritional status, metabolic needs)
8
Q
Example of cell type affecting injury extent (cardiac vs skeletal muscle)
A
cardiac myocytes are more sensitive than skeletal myocytes and will be injured more when exposed to same low oxygen environment
9
Q
Aetiologies (causes) of cell injury
A
hypoxia, ischaemia, physical agents, chemicals/drugs, infections, immunological reactions, nutritional imbalance, genetic defects
10
Q
Hypoxia definition
A
oxygen deficiency
11
Q
Causes of hypoxia
A
anaemia, respiratory failure
12
Q
How does hypoxia affect cells?
A
disrupts oxidative respiratory process which greatly decreases ATP / cell energy supply
13
Q
How do cells adapt to hypoxia?
A
release energy via anaerobic mechanisms (limited)
14
Q
Ischaemia definition
A
reduction in blood supply to tissue (depletion of oxygen and nutrients)
15
Q
Cause of ischaemia
A
blockage of arterial supply or venous drainage e.g. atherosclerosis
16
Q
Which imposes more severe/rapid damage: hypoxia or ischaemia?
A
Ischaemia
17
Q
Why does ischaemia cause more severe/rapid damage than hypoxia?
A
Ischaemia causes oxygen AND nutrient depletion so anaerobic respiration also stops (no glucose supply)
18
Q
What physical agents can cause cell injury?
A
mechanical trauma, extreme temperatures, ionising radiation, electric shock
19
Q
How can mechanical trauma lead to cell injury?
A
by affecting cell membranes and cell structure
20
Q
How can extreme temperatures (hot/cold) cause cell injury?
A
affects proteins and chemical reactions
21
Q
How can ionising radiation cause cell injury?
A
can lead to DNA damage that is irreparable by the cell. Can lead to cancer
22
Q
How can electric shock cause cell injury?
A
causes burns
23
Q
Which physical agent can cause cell injury that is not immediately apparent?
A
ionising radiation (DNA damage can appear as cancer years down the line)
24
Q
What are the infectious agents that can cause cell injury?
A
bacteria, viruses, fungi, parasites, prions
25
What chemicals/drugs can cause cell injury?
simple chemicals, poisons, occupational hazards, alcohol, smoking, recreational drugs
26
How can simple chemicals (e.g. glucose) cause cell injury?
an excess of the chemical (e.g. glucose) can cause an osmotic disturbance
27
How can poisons (e.g. cyanide) cause cell injury?
cyanide blocks oxidative phosphorylation leading to ATP deprivation
28
Example of an occupational hazard that can cause inflammation
asbestos
29
Examples of immunological reactions that can cause cell injury
anaphylaxis (severe type I hypersensitivity), autoimmune reactions (e.g. type II - haemolytic anaemia, type III - antigen-antibody immune complexes embedded in endothelium)
30
How do immunological reactions cause cell injury?
due to inflammation (complement - membrane attack complexes, clotting, neutrophil products e.g. enzymes, ...)
31
Example of cellular injury that occurs due to inadequate intake of a specific nutrient (cause cell injury)
scurvy, rickets
32
Which nutrient is deficient in scurvy?
vitamin C
33
Which nutrient is deficient in rickets?
vitamin D
34
Example of a disease that occurs due to a generalised inadequate nutrient intake (cause cell injury)
anorexia
35
Examples of diseases that occur due to excess intake of a specific nutrient (leads to cell injury)
hypervitaminosis A/D
36
Example of a disease that occurs due to a generalised excessive nutrient intake (cause cell injury)
obesity
37
What genetic defects can cause cell injury?
sickle cell anaemia, inborn error of metabolism, cancer
38
What are inborn errors of metabolism?
genetic disorders that cause failure of a metabolic pathway due to a lack of enzyme causing accumulation of the substrate
39
Why must individuals of an Afro-Caribbean background be screened for sickle cell anaemia before undergoing general anaesthetic?
low oxygen tension during GA can cause individuals to undergo sickling
40
What cellular processes can be disrupted due to reversible cell injury?
aerobic respiration/ATP synthesis, plasma membrane integrity, enzyme and structural protein synthesis, DNA maintenance
41
What 2 morphological changes can occur during reversible cell injury?
cloudy swelling or fatty change
42
What happens during cloudy swellings?
Lack of energy leads to pumps in the plasma membrane failing. Cells are incapable of maintaining ionic and fluid homeostasis. Leads to influx of Na+ and water, and accumulation of intracellular metabolites. Cells swell
43
What happens during fatty change?
There is a disruption of fatty acid metabolism so triglycerides cannot be released from the cell. Causes accumulation of lipid vacuoles in cytoplasm.
44
Causes of fatty change
toxic and hypoxic injury (alcohol abuse, diabetes, obesity)
45
Which organ is particularly affected by fatty change?
liver (can also occur in heart)
46
What is the macroscopic appearance of a liver that has undergone fatty change?
enlarged and pale liver
47
What happens at the 'point of no return' following reversible fatty change?
cells cannot accumulate any more triglycerides which leads to cirrhosis/fibrosis
48
What reversible changes can occur during cell injury?
swelling of cell and organelles, blebbing
49
What is blebbing?
A process where part of the cell breaks off
50
What changes occur inside the cell at the 'point of no return'?
extreme organelle swelling, violent blebbing (cell damage becomes permanent)
51
What cellular changes occur in irreversible injury?
membrane rupture, dispersal of organelles (prompts inflammation), lysosome breakdown
52
Does necrosis require energy?
no
53
What is necrosis?
cell death
54
Cause of necrosis
irreversible cell injury usually due to pathology
55
How is the cell broken down during necrosis?
lysosomes digest cell and dispersed organelles (due to cell membrane rupture) are removed via phagocytosis by macrophages
56
What type of response occurs in tissue surrounding necrosis?
inflammatory response
57
What are the nuclear changes that occur during necrosis?
pyknosis, karyorrhexis, karyolysis
58
What is a useful microscopic sign that a cell is necrotic?
there is a loss of the blue staining nucleus
59
What happens during pyknosis (stage of necrosis)?
nucleus shrinks and becomes darker staining
60
What is the term used to describe the fragmentation of the nucleus during necrosis?
karyorrhexis
61
What happens during karyolysis?
the blue staining DNA in nucleus is digested by endonucleases and the blue staining fades away
62
What are the cytoplasmic changes that occur during necrosis?
cytoplasm either appears paler due to swelling or more eosinophilic (pink) due to denaturation of cytoplasmic structural and enzyme proteins
63
What are the 3 main types of necrosis?
1. coagulative necrosis
2. liquefactive necrosis (colliquative)
3. caseous necrosis
64
What is the most common type of necrosis?
coagulative necrosis
65
Example of coagulative necrosis
myocardial infarction
66
Infarct definition
localised area of coagulative necrosis
67
What is the microscopical appearance of coagulative necrosis?
eosinophilic cells with no nucleus and a preserved structure (for a few days)
68
Why is the architecture of tissue that has undergone coagulative necrosis preserved for a few days?
enzymes have denatured therefore there is no proteolysis of the dead cells
69
How are the cells broken down in coagulative necrosis?
by lysosomes of leukocytes
70
What is the cause of coagulative necrosis?
ischaemia - (thrombus can cause) blocked blood supply to tissue leading to cell death due to lack of oxygen / nutrients
71
What are the dark spots that appear on a slide of tissue that has undergone coagulative necrosis?
inflammatory cells (leukocytes)
72
What is the gross texture of tissue that has undergone coagulative necrosis?
grossly firm in texture
73
What is the more common term used to describe liquefactive necrosis?
pus
74
Definition of colliquative necrosis
digestion of dead tissues into a liquid viscous state
75
Causes of liquefactive necrosis
focal bacterial or fungal infections (abscess)
76
What is an abscess?
collection of pus
77
What is the gross appearance of liquefactive necrotic tissue?
thick, pale yellow coloured liquid
78
What type of necrosis does CNS necrosis due to hypoxia often manifest as?
liquefactive necrosis (colliquative)
79
What is the gross appearance of caseous necrosis?
friable white appearance (like cheese)
80
Example of infection in which caseous necrosis occurs
tuberculous infection
81
What is the microscopic appearance of caseous necrosis?
granular debris (mass apoptosis) and granuloma-fragmented cells surrounded by inflammatory cells
82
What cells exist in a caseous necrosis granuloma?
chronic inflammatory cells, multinucleated giant cells, fibroblasts
83
What is the name of a form of necrosis that involves both coagulative and liquefactive necrosis?
gangrenous necrosis
84
What is gangrenous necrosis?
coagulative necrosis with superimposed anaerobic bacterial infection - liquefactive necrosis
85
What is the sequalae for gangrenous necrosis?
amputation
86
What is fat necrosis?
focal areas of fat destruction
87
What is the cause of fat necrosis?
acute pancreatitis or trauma may lead to the release of activated pancreatic enzymes which liquefy fat cells
88
What special type of necrosis can be seen in immune reactions in blood vessels?
fibrinoid necrosis
89
What happens during fibrinoid necrosis?
antigen-antibody immune complexes are deposited in artery walls together with fibrin that leaks out of the vessels
90
What is the appearance of fibrinoid necrosis in H&E stain?
bright pink (eosinophilic) and amorphous substance
91
What are the effects of necrosis?
function loss (depends on organ/tissues) and inflammation
92
Why does necrosis cause inflammation?
release of cell contents activates inflammation so that cell remains are then phagocytosed
93
What happens to the necrotic area?
replaced by a scar (undergoes organisation or repair)
94
What happens if the necrotic remains are not removed?
calcium salts may be deposited in necrotic tissue (esp fat necrosis)
95
What part of the cell reveals whether the cell is vital or non vital?
nucleus
96
How may the nuclei of non-vital cells appear?
pyknosis (small and darkly staining), karyorrhexis (nuclei fragmented), karyolysis (nuclear fading)
97
What part of the cell explains how cells have died?
cytoplasm
98
What cell injuries can cause coagulation necrosis (except in CNS where liquefactive necrosis occurs)?
hypoxia or free radicals
99
What type of necrosis occurs due to denatured cytoplasm?
coagulative necrosis (except in CNS)
100
What cell injuries can cause liquefactive necrosis?
strogn acids/alkalis, clostridia, snake venom, neutrophils
101
What happens to cells when they undergo liquefaction necrosis?
hydrolysed
102
What cell injuries cause caseous necrosis?
tuberculosis or some fungi
103
What happens to cells that undergo caseous necrosis?
mass apoptosis (forms granuloma)
104
What happens to cells that undergo fat necrosis?
saponified and Ca deposited
105
What is apoptosis?
genetically programmed cell death
106
Function of apoptosis
has an important physiological role by eliminating unwanted cells
107
When can apoptosis occur?
pathological situations or as part of normal physiology
108
Does apoptosis require energy?
yes
109
Which type of cell death requires energy?
apoptosis (not necrosis)
110
Which type of cell death causes inflammation?
Necrosis (apoptosis does not cause inflammation)
111
What is the appearance of apoptotic cells with H&E?
cells are smaller and more darkly stained
112
What are potential pathological triggers of apoptosis?
hypoxia/ischaemia, viral infection, DNA damage
113
How can a viral infection trigger apoptosis?
cytotoxic T-lymphocytes contain enzymes that can induce apoptosis
114
How can DNA damage trigger apoptosis?
if DNA damage is irreparable, Tp53 gene synthesises the protein p53 which triggers apoptosis
115
Which gene is known as the 'guardian of the genome'?
Tp53 (tumour suppressor gene)
116
What enzymes trigger apoptosis?
caspases
117
What is the physiological role of apoptosis during embryo/fetal development?
deletion of cell populations during embryogenesis
118
What is the physiological role of apoptosis in females during ageing?
hormone change dependent involution of uterus, breasts, ovaries
119
What is the physiological role of apoptosis in proliferating cell populations?
to maintain constant cell numbers (e.g. in epithelium)
120
What are the physiological roles of apoptosis within the immune system?
deletion of inflammatory cells following immune response, deletion of self reactive B and T lymphocytes
121
What diseases can result from excess apoptosis?
degenerative diseases
122
What diseases can result from too little apoptosis?
cancer
123
What are the cellular morphological changes that occur during apoptosis?
cell shrinkage, chromatin condenses and nucleus fragments (becomes darker staining), cytoplasmic blebs form which break off into apoptotic bodies, phagocytosed
124
Why does apoptosis not trigger inflammation (unlike necrosis)?
during apoptosis, the cell contents are still contained within the plasma membrane whereas in necrosis the membrane ruptures
125
What is the difference that occurs in cell size during necrosis compared to apoptosis?
the cell is enlarged in necrosis and reduced in apoptosis
126
What 2 groups of substances can accumulate in cells?
excessive normal cellular constituent or abnormal endogenous/exogenous material
127
Examples of normal cellular constituent that can undergo intracellular accumulation
water, lipid (fatty change), glycogen
128
Examples of abnormal endogenous/exogenous materials that can accumulate intracellularly
carbon, silica, metabolites, cholesterol
129
Where can intracellular accumulation occur?
nucleus or cytoplasm
130
Atherosclerosis definition
accumulation of cholesterol in macrophages and smooth muscle cells in blood vessel walls
131
Where can cholesterol accumulation occur?
in blood vessel walls (atherosclerosis), sites of haemorrhage and necrosis
132
What type of cells are found in areas of cholesterol accumulation?
foam cells
133
What are foam cells?
macrophages that have ingested lipids (large, pale cells)
134
What is amyloid?
a fibrillar protein material deposited due to pathologic processes that lead to increased production of amyloid
135
Where is amyloid deposited?
extracellular location (mostly on basement membrane) in various tissues and organs
136
Examples of tissues and organs where amyloid deposition can occur
kidney and tongue
137
What are the different types of amyloid?
AL (amyloid light chain)
AA (amyloid associated)
AB (beta)
138
Where is AL (amyloid light chain) derived from?
light chain immunoglobulins from plasma cells
139
Where is AA (amyloid associated) derived from?
proteins synthesised in the liver
140
Which disease has AB (beta) deposition?
Alzheimer's disease (deposition in brain)
141
What are the possible stimuli for amyloid deposition?
chronic inflammation, multiple myeloma, ageing, drug abuse
142
What is multiple myeloma?
type of bone marrow cancer caused by malignant plasma cells (produce lots of light chain Ig leading to AL deposition)
143
What stain should be used to identify amyloid?
special stains e.g. congo red has an affinity for amyloid
144
Why is H&E staining not suitable for identifying amyloid?
amyloid has a microscopically pink hyaline appearance so is difficult to identify with H&E
145
What is pathological pigmentation?
Build up of pigmented substances in cytoplasm
146
What are the 2 types of pathological pigmentation?
endogenous and exogenous pigmentation
147
What colour do all endogenous pigmentations appear?
brown
148
What are the different types of endogenous pigmentation?
lipofuscin, melanin, haemosiderin, bilirubin
149
What is lipofuscin?
a type of pigment consisting of cellular lipid breakdown products formed by wear and tear of cells
150
What is localised bruising termed?
haemosiderin
151
Example of a stimulus that increases melanin pigmentation
sun - increases melanocytes' activity resulting in increased melanin production (tan)
152
What are the potential exogenous pathological pigments?
carbon deposition, tattoos, heavy metal salts (e.g. lead), pigmentation associated with IV drug use
153
What is the most common exogenous pathological pigmentation?
carbon deposition
154
Where does carbon deposition occur?
in macrophages in alveoli of lungs
155
Causes of carbon deposition
inhaled soot/smoke (e.g. coal workers can have severe C deposition)
156
What is the name of the black pigment that results due to a large volume of C deposition?
anthracosis
157
What is the name of a group of lung conditions where fibrosis occurs due to severe deposition?
pneumoconiosis
158
What are the 2 types of pathologic calcification?
dystrophic and metastatic calcifications
159
What are dystrophic calcifications?
deposits of calcium phosphate in necrotic tissue. serum calcium is normal
160
What are the serum calcium levels in dystrophic calcification?
normal serum calcium levels
161
Example of disease where dystrophic calcification can occur
valvular heart disease
162
What are metastatic calcifications?
deposits of calcium salts in normal, vital tissue with raised serum calcium levels (excess Ca causes deposition)
163
What is the serum calcium level like in metastatic calcification?
raised serum calcium levels
164
Where does metastatic calcification often occur?
in connective tissue of blood vessels
165
How may metastatic calcification lead to compromised tissue function?
calcium salts in blood vessel walls can affect elasticity
166
What is the term used to describe raised serum calcium?
hypercalcaemia
167
Causes of raised serum calcium
1. increased levels of PTH
2. destruction of bone tissue
3. excess vitamin D
4. renal failure
168
What is the term used to describe increased levels of parathyroid hormone?
hyperparathyroidism
169
What is a potential cause of hyperparathyroidism?
parathyroid gland tumour (benign tumours)
170
How does PTH increase serum calcium?
PTH activates osteoclasts leading to bone resorption (osteoclastogenesis) which releases Ca
171
What are possible causes of bone tissue destruction that can lead to hypercalcaemia?
hyperparathyroidism, leukaemia, malignant metastasis to bone, immobilisation (disuse)
172
How can renal failure result in hypercalcaemia?
renal failure may cause secondary hyperparathyroidism
