Cell Injury Flashcards
(109 cards)
1
Q
What does the degree of cell injury depend on? (3)
A
- type of injury
- severity of injury
- type of tissue
2
Q
What is hypoxia and what can it cause?
A
Deficiency in the amount of oxygen reaching tissues
Can caused cell injury
3
Q
What kind of things can cause cell injury? (9)
A
Hypoxia Toxin Physical agents Radiation Chemical agents and drugs Micro-organisms Immune mechanisms Dietary insufficiencies and deficiencies/diet excess Genetic (in born errors of metabolism)
4
Q
Give some examples of the physical agents that might cause cell injury (4)
A
Direct trauma
Extreme temps
Changes in pressure
Electric currents
5
Q
What is the difference between hypoxia and ischaemia? Which is worse?
A
Hypoxia is a deficiency in the amount of oxygen reaching tissue but ischaemia is a deficiency in the blood supply to tissue
Ischaemia is worse
6
Q
Name and describe the 4 types of hypoxia
A
- Hypoxaemic hypoxia (is arterial content of oxygen is low)
- Anaemic hypoxia (decreased ability of haemoglobin to carry oxygen)
- Ischaemic hypoxia (interruption to blood supply)
- Histiocytic hypoxia (inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes)
7
Q
Give a cause of Hypoxaemic hypoxia
A
Reduced inspired pO2 at altitude
Reduced absorption secondary to lung disease
8
Q
Give a cause of anaemic hypoxia
A
Anaemia
CO poisoning
9
Q
Give a cause of ischaemic hypoxia
A
Blockage of blood vessel
Heart failure
10
Q
Give a cause of histiocytic hypoxia
A
Cyanide poisoning
11
Q
The degree of damage caused by hypoxia varies in different tissues, how long can neurones and fibroblasts survive before they become damaged?
A
Neurone-few minutes
Fibroblasts-few hrs
12
Q
How does the immune system damage the body’s cells?
A
Hypersensitivity reactions (host tissue is injured secondary to an overly vigorous immune reaction)
Autoimmune reactions (failure to distinguish self from foreign)
13
Q
Give an example of a condition caused by hypersensitive reactions, when the immune system damages the body’s cells
A
Urticaria (hives)
14
Q
Give an example of an autoimmune reaction, in which the immune system causes damage to the body’s cells
A
Grave’s disease of thryoid
15
Q
Which cellular components are most susceptible to injury? (4)
A
Membranes (plasma/organellar)
Nucleus (DNA)
Proteins (structural/enzymes)
Mitochondria (oxidative phosphorylation)
16
Q
What is happening at a molecular level in hypoxia?
A
- oxygen levels are decreased
- oxidative phosphorylation in mitochondria reduces
- less ATP is produced (levels reach 5-10% of norm), causes many things:
1) reduce in Na+/K+ ATPase = influx of Ca2+, H2O and Na+, efflux of K+ =cellular swelling, blebbing, myelin figures appear etc
2) rate of glycolysis increases (anaerobic respiration)=pH is lowered + glycogen stores decrease
3) other effect- detachments of ribosomes=decrease in protein synthesis=lipid deposition
17
Q
What happens as result of prolonged hypoxia?
A
Irreversible results!
Increased cytosolic Ca2+ (due to lack of Na+ pump action)
Ca2+ inappropriately activates multiple enzymes:
1)ATPase=decreased ATP
2)phospholipase=decreased phospholipids
3)protease=disruption of membrane and cytoskeletal proteins
4)endonucleases=nuclear chromatin damage
18
Q
Why do you often see the same result in cells in non hypoxia situations? Ie extreme cold- frostbite, free radicals
A
Often membranes can be damaged by extreme temps which allows for the influx of water and Ca2+ and causes the same issues
Free radicals cause damage to membranes also
19
Q
What are free radicals?
A
Reactive oxygen species
Single unpaired electrons
V. Unstable configuration
React with other molecules to stabilise themselves but produce free radicals in the process
20
Q
Name the 3 types of free radicals that are of particular biological significance in cells
A
Hydroxyl (most dangerous) OH
O2- (superoxide)
H2O2 (hydrogen peroxide)
21
Q
Give some examples of chemical agents and drugs that can cause cell injury (9)
A
Glucose/salt in hypertonic solutions Oxygen in high conc Poisons Insecticides Herbicides Asbestos Alcohol Illicit drugs Therapeutic drugs
22
Q
Give a summary of hypoxia cell injury (14 steps)
A
1)cell is deprived of oxygen
2)Mitochondrial ATP production stops.
3)The ATP-driven Na+ K+ ATPase pumps runs down.
4)Sodium and water seep into the cell.
5)The cell swells, and the plasma membrane is stretched.
6)Glycolysis enables the cell to limp on for a while (anaerobic respiration)
7)The cell initiates a heat-shock (stress) response, which
will probably not be able to cope if the hypoxia persists.
8)The pH drops as cells produce energy by glycolysis and lactic acid
accumulates.
9)Calcium enters the cell. (Voltage changes across membrane due to abnormal movement of ions)
10)Calcium activates enzymes which damage cell and organelles
11)The ER and other organelles swell. 12) Enzymes leak out of lysosomes and these enzymes attack cytoplasmic components.
13)All cell membranes are damaged and start to show blebbing.
14)At some point the cell dies, possibly killed by the burst of a bleb.
23
Q
What is a free radical?
A
Something that has an unpaired electron- high energy
24
Q
When are free radicals produced? (4)
A
Chemical and radiation injury
Ischaemia-repercussion injury
Cellular aging
High oxygen concentration
25
What in particular do free radicals attack within the cell?
The cell membranes causing lipid peroxidation (oxidation of lipids- being degraded)
26
What is the system that the body has to prevent injury from free radicals?
Anti-oxidant system
27
When is a tissue said to be in oxidative stress?
When there is a build up of free radicals
28
What 3 things does the anti-oxidant system consist of?
Enzymes
Free radical scavengers
Storage proteins
29
Give examples of enzymes in the anti-oxidative system
Superoxide dismutase (SOD): O2- -> H2O2
Catalase: H2O2->O2 + H20
Peroxidases: H2O2->O2 + H2O
30
Give examples of free radical scavengers
Vitamin A
Vitamin C
Vitamin E
Glutathione
31
The anti-oxidative system has storage proteins, what are these?
These are proteins that sequester transition metals in the extracellular matrix.
32
What mechanism can a cell use to repair injury to proteins within cells?
Heat shock proteins
33
What do heat shock proteins do? Give an example
Mend other proteins
Bind to and guide them through the process of refolding/repair
Also called unfoldases or chaperonins
Ubiquitous
34
What cell morphology would you see in hypoxia under a light microscope?
- Cytoplasmic change
- Nuclear changes
- Abnormal cellular accumulation
35
Describe the appearance of a cell injured during hypoxia under a light microscope
Pale pink and swollen- membranes aren't working so well and so water and Na+ gets in
36
Describe what you might see in a dead cell during hypoxia under a light microscope
cytoplasm goes pink- it is deeply stained as proteins have coagulated and clumped, therefore have picked up eosin stain strongly
There are nuclear changes also:
Pyknosis-Nucleus shrinks and becomes very dark
Karyorrhexis- nucleus breaks up (follows pyknosis)
Karyolysis- complete dissolution of nuclei (follows karyorrhexis)
37
Name the 3 types of nuclear changes one might observe when looking down a light microscope at a dead cell after hypoxia
Pyknosis- shrinking and darkening
Karyrrhexis- breaks up
Karyolysis- disappears
38
Under an electron microscope it is possible to view both reversible and irreversible cellular changes that occur during hypoxia. Describe some of the reversible changes that are visible (4)
- swelling of cell and organelles (due to Na+/K+ pump failure)
- blebbing (occurs as a result of swelling)
- clumped chromatin (due to reduced pH)
- ribosome separation from ER (due to failure of energy-dependent process of maintaining ribosomes in correct position)
39
Under an electron microscope it is possible to view both reversible and irreversible cellular changes that occur during hypoxia. Describe some of the irreversible changes that are visible (7)
- increased cell swelling
- nuclear changes (pyknosis, karyorrhexis, karyolysis)
- swelling and rupture of lysosomes (reflects membrane damage)
- membrane defects
- appearance of myelin figures 9which are damaged membranes)
- lysis (rupture) of ER due to membrane defects
- amorphous densities of swollen mitochondria
40
Define oncosis
Cell death with swelling, the spectrum of changes that occur prior to death in cells injured by hypoxia and some other agents
41
Define apoptosis
Cell death with shrinkage, cell death induced by a regulated intracellular program where a cell activates enzymes that degrade its own nuclear DNA and proteins
42
Define necrosis
In a living organism the morphologic changes that occur after a cell has been dead some time (eg 24 hrs)
**NB: necrosis is an appearance and not a process- it is NOT a type of cell death
43
Why do you get blebbing during oncosis?
The cytoskeleton is being broken down by proteases (triggered by Ca2+ influx, cell swells because membrane is no longer held tightly in shape
44
How is necrotic tissue removed?
By enzymatic degradation and phagocytosis by white cells
45
What is dystrophic calcification?
Necrotic tissue that calcified having been left by white blood cells
46
What are the two main types of necrosis? Give a brief description of the types
Coagulation- solid tissues (a lot of Connective tissue support) and liquifactive - loose tissues (little c.t), can happen in presence of many neutrophils (in areas of inflammation due to chemicals from immune cells)
47
When a cell is dying its proteins can undergo one of 2 things, name the two processes that might happen and what kind of necrosis is seen as a result
Denaturation (and resulting proteins coagulate)= coagulative necrosis
Autolysis (proteins undergo dissolution by the cells own enzymes)= liquifactive necrosis
48
What are the two less common types of necrosis?
Caseous (structureless debris- bot uniform ghost outlines though) - can look like cheese
associated with infection (especially TB)
fat necrosis (collections of fat)
49
What does coagulative necrosis look like?
- coagulation of proteins- dark staining
| - ghost outlines
50
What does liquefactive necrosis look like?
Very little left
Proteins and everything else has been all but dissolved
(Often looks like a hole)
51
Define the term gangrene
Necrosis visible to the naked eye
52
Define infarction
Necrosis caused by reduction in arterial blood flow (can lead to hypoxia )
A cause of necrosis
Can result in gangrene
53
Define the term 'infarct'
An area of necrotic tissue which is the result of loss of arterial blood supply
An area of ischaemic necrosis
54
What is the difference between wet and dry gangrene? Which type does gas gangrene come under?
Dry- necrosis modified by exposure to air (coagulative necrosis)
Wet- necrosis modified by infection (liquefactive necrosis)
Gas gangrene is a type of wet gangrene
55
Define the term gas gangrene
wet gangrene where the tissue has become infected with anaerobic bacteria that produce visible and palpable bubbles of gas within the tissues.
(bacteria spread quickly into blood supply)
Very dangerous!
56
What are the two types of infarction? What do they refer to?
Red and white
Indicated how much haemorrhage there is into the infarct
57
When might a white (anaemic) infarct occur?
In solid organs after conclusions of 'end' arteries
Often wedge shaped
Coagulative necrosis
58
When might a red (haemorrhagic) infarct occur?
Where there is extensive haemorrhage into dead tissue
Loose tissue- often in tissues with a dual blood supply- there is a bleed into the infarct because the vessels aren't well supported
59
Many molecules are released by injured, dying and dead cells as their membranes lose integrity, what are the consequences of this release? (3)
*the consequences may not necessarily be bad*
- cause local irritation and inflammation
- general toxic effects on body
- can appear high concentrations in the blood and can be measured- aid diagnosis
60
Give an example of a molecule released during cell injury/death (3)
- potassium
- enzymes (can indicate organ involved and extent, Timing and evolution of the tissue damage)
- myoglobin (releases form dead myocardium and striated muscle)
61
What are the commonest causes of infarctions?
Thrombosis- blood clot within vessel
Embolism- lodging of an embolus (a blockage-causing piece of material, inside a blood vessel)
Putting external pressure on tissue- restricting blood flow
62
What does the severity of infarction depend upon?
- alternative blood supply
- speed of ischeamia
- tissue involved
- oxygen content of the blood
63
What is ischaemia-repercussion injury?
Reperfusion (reoxygenation) injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen (anoxia, hypoxia).
Only occurs if the tissue is not yet necrotic
64
What are the possible causes of an ischaemia-reperfusion injury?
- increased production of oxygen free radicals
- increased number of neutrophils resulting in more inflammation and increased tissue injury (can cause necrosis)
- delivery of complement proteins and activation of the complement pathway
65
What ion build up can tumour lysis syndrome cause?
Hyperkalaemia
66
What is rhabdomyolysis? What is a sign of this?
condition in which damaged skeletal muscle breaks down rapidly
Happens during massive trauma/extreme exercise/extreme conditions
-The urine may be dark, often described as "tea-colored", due to the presence of myoglobin.
67
When might apoptosis occur?
When there is damage affecting the cell's DNA (irreversible damage)
68
Describe the appearance of a cell going through apoptosis under a light microscope
Shrunken and appear intensely eosinophilic, there is chromatin condensation, pyknosis (non-random, internucleosomal cleavage of DNA) and karyorrhexis are seen.
69
Describe the appearance of a cell undergoing apoptosis under an electron microscope
Budding of apoptotic bodies (which will be removed by macrophage phagocytosis)
70
What are the 3 key stages of apoptosis?
Initiation
Execution
Degradation/phagocytosis
71
When might apoptosis occur physiologically?
- maintain steady state
- hormone controlled involuted now (eg women in menopause- smaller ovaries, hormones stopped)
- embryogenesis (formation of limbs and fingers)
72
When does apoptosis occur pathologically?
- cytotoxic T cell killing of virus-infected or neoplastic cells
- when cell has damage
- graft versus host disease
73
Initiation and execution of apoptosis is triggered by two mechanisms, name those mechanism
Intrinsic and extrinsic
74
How is the intrinsic pathway in apoptosis initiated?
Initiating signals from within the cell
75
What is a trigger for the intrinsic pathway of apoptosis?
- irreparable DNA damage
| - withdrawal of growth factors or hormone (like in ovaries of menopausal women)
76
How is the apoptotic intrinsic pathway carried out?
- p53 is activated
- outer mitochondrial membrane becomes leaky
- cytochrome C is released
- causes activation of caspases (family of protease enzyme)
77
How is the apoptotic extrinsic pathway initiated?
By extracellular signal
78
Why would the apoptotic extrinsic pathway be triggered?
Cells that are a danger eg tumour cells, virus infected cells
79
How is the apoptotic extrinsic pathway carried out- use TNF alpha as an example
- TNF alpha secreted by T killer cells
- bind to cell membrane receptors (death receptor)
- results in activation of caspases
80
How are apoptotic bodies phagocytosed?
By phagocytes or neighbouring cells, because they can recognise the proteins expressed on the apoptotic body's membrane
81
What are the difference between oncosis/necrosis and apoptosis, in terms of pattern of cells involved?
Oncosis- contiguous groups of cells
| Apoptosis-single cells
82
What are the difference between oncosis/necrosis and apoptosis, in terms of cell size?
Oncosis- enlarged
| Apoptosis- reduced
83
What are the difference between oncosis/necrosis and apoptosis, in terms of the plasma membrane?
Oncosis- disrupted, early lysis , blebbing
| Apoptosis- in tact, budding
84
What are the difference between oncosis/necrosis and apoptosis, in terms of cellular contents?
Oncosis- enzymatic digestion, leak out of cell
| Apoptosis- intact, realised in apoptotic bodies
85
What are the difference between oncosis/necrosis and apoptosis, in terms of adjacent inflammation?
Oncosis- frequent
| Apoptosis- none
86
What are the difference between oncosis/necrosis and apoptosis, in terms of physiological or pathological role?
Oncosis- invariably pathologic
| Apoptosis- often physiologic- means of elimination unwanted cells, may be pathology after some form of cell injury
87
What do abnormal cellular accumulations derive from?
- cell's own metabolism
- the extracellular space (spilled blood eg)
- the outer environment (dust eg)
88
What are the 5 main groups of intracellular accumulations?
- water and electrolytes
- lipid (triglycerides and cholesterol)
- proteins (eg Mallory' hyaline, alpha-1 antitrypsin)
- 'pigments' (exogenous and endogenous)
- carbohydrates
89
What is the term used to describe local pathological calcification?
Dystrophic calcification
90
What is the term used to describe general calcification?
Metastic calcification
91
Where might dystrophic calcification occur? (4)
- In areas of dying tissue
- Artherosclerotic plaques
- In aging or damaged heart valves
- Tuberculous lymph nodes
92
Why does dystrophic calcification occur?
Local change/disturbance causes the formation of hydroxyapatite crystals (which are mineral forms of Ca2+)
93
Why does metastatic calcification occur?
Hypercalcaemia secondary to disturbances in calcium metabolism
(Hydroxyapatite crystals are deposited in normal tissues throughout the body)
94
What causes hypercalcaemia?
- Increased secretion of parathyroid hormone (PTH) resulting in bone reabsorption
- destruction of bone tissue (eg being immobile for long periods of time)
95
What is steatosis?
Accumulation of triglycerides (often seen in the liver- fatty liver)
96
What is fluid accumulating in cells called?
Hydropic swelling
97
Why does hydropic swelling occur? And where might this be a particular issue?
Loss of blood supply leads to decreased oxygen tension inside cell and results in ATP depletion. There is also loss of oxidative phosphorylation causing decreased ATP generation and failure of Na+K+ pump. This leads to increased intracellular sodium and water along with increased extracellular potassium, leading to cellular swelling.
Problem in brain
98
Why are there very few proteins in injured cells?
Because there is a reduced level of ATP meaning ribosome are no longer held onto the ER and as a result there is little protein production within injured cells
99
When does cholesterol accumulate in the cells?
When the liver is not functioning properly, (can only be eliminated by the liver).
100
Cholesterol can often accumulate in smooth muscle cells and macrophages in artherosclerotic plaques, what does this form?
Foam cells
101
What are foam cells?
Fat filled macrophages:
Foam cells are formed when the body sends macrophages to the location of a fatty deposit on the blood vessel walls. The macrophage surrounds the fatty material in an attempt to destroy it. The cell becomes filled with lipids (fats). The lipids surrounded by the macrophage give it a "foamy" appearance.
102
What occurs when there is cholesterol build up in macrophages of the skin and tendons with people with hereditary hyperlipidaemias?
xanthomas
| Yellow swellings-look like blisters
103
What is Mallory's hyaline? What is a cause of this?
Damaged keratin filaments- clumped together
Alcoholic liver disease
104
Briefly describe what is mans to have a alpha1-antitrypsin deficiency, what is one possible outcome of this particular deficiency?
-Liver produces incorrectly folded a1-antitrypsin protein
-Cannot be packages in ER
-accumulates in ER
Systemic deficiency
Can lead to proteases in the lungs acting unchecked resulting in emphysema
(**under a microscope you would see a lot of pink proteins)
105
Give some examples of pigments accumulating in the cells (2)
Carbon/coal dust soot
| Tattooing ink
106
You can get accumulation of endogenous pigments- for example haemosiderin, why might this accumulate?
Because there is a systemic/local excess of iron eg bruise- where blood leaks into tissues and haemosiderin is formed due to excess of iron
107
What is hereditary haemochromatosis?
- Inherited
- results in increases intestinal absorption of dietary iron
- iron is deposited around body, causing inflammation and scarring
- patients often have golden colour to skin
- treatment:repeated bleeding
- symptoms: liver damage, heart dysfunction, multiple endocrine failures
108
What is the cause of jaundice?
- Accumulation of bilirubin (bright yellow)
- excreted in bile
- if bile flow is obstructed or overwhelmed, bilirubin in blood rises=jaundice
109
What are the mechanisms of intracellular accumulations?q
- abnormal metabolism
- alteration in protein folding and transport
- deficiency of critical enzymes
- inability to degrade phagocytosed particles
