1
Q
2 state of cell in response to stress?
A
Homeostasis
|
- Adaptation
- Injury
2
Q
What is adaptation of cells in response to injury?
A
Excess physiologic or pathological stress may force the cell to a new steady state- Adaptation
3
Q
How injury happens?
A
Too much stress exceeds the cells adaptive capacity- injury
4
Q
Reversibility of cell injury
A
- Reversible
2. Irreversible
5
Q
Reversibility of cell injury depends on??
A
- Severity
2. duration
6
Q
The principle adaptive response are?
A
- Hypertrophy
- Hyperplasia
- Atrophy
- Metaplasia
7
Q
Cell death results from?
A
- Ishemia ( lack of blood flow )
- Infection
- Toxin
- Immune reaction
- Hypoxemia
8
Q
Illustrate the relationship between normal, adapted and reversible and irreversibly injured cells by the response of to different type of stress
A
- Hypertension or stenotic valve - hypertrophy
- If. Increase demand is not relieve or if myocardium is subjected to reduce blood flow(ischemia) then the muscle cells may undergo cell injury
- Reversibly injured if the stress is mild
9
Q
What is and Example of physiologic adaptation?
A
It is usually represent responses of cells to normal stimulation by hormones or endogenous chemical medicators.
Eg- the hormone-induced enlargement of the breast and uterus during pregnancy
10
Q
What is pathologic adaptation?
A
Pathologic adaptations are responses to the stress that allow cells to modulate their structure and function and thus escape injury.
11
Q
What is hypertrophy?
A
It is an increase in the size of cells resulting in the increase size of organ.
12
Q
Types of hypertrophy?
A
- physiologic
- pathologic
13
Q
How the enlargement of uterus occurs?
A
The massive physiologic enlargement of the uterus during pregnancy occurs as a result of
- estrogen-stimulated smooth muscle hypertrophy
- smooth muscle hyperplasia
14
Q
Where only hypertrophy occurs?
A
- striated muscle cells in skeletal muscle and heart because they have limited Capacity to divide
15
Q
Weightlifter undergo which process?
A
Hypertrophy
16
Q
Example of pathologic cellular hypertrophy?
A
Cardiac enlargement that occurs with hypertension or aortic valve disease.
17
Q
Mechanism during cardiac hypertrophy?
A
It involves at least two types of signals
- mechanical triggers-stretch
- tropic triggers-activation of alpha adrenergic receptors
These stimuli turn on signal transduction pathways
That lead to the induction of a number of a genes
Which in turn stimulate synthesis of numerous cellular proteins (growth factors & structural proteins)
Synthesis of more protein and myofilaments
Improve performance
Balance between demand and cell functional capacity
18
Q
What is cell injury?
A
Cell injury result when cells are stressed so severely that no longer able to adapt or cells are exposed to inherently agents or suffer from intrinsic abnormalities.
19
Q
Common causes of cell injury?
A
- Hypoxia
- Physical agents
- Chemical agents
- Infections
- Immunological cause- autoimmunity
- Nutritional imbalance
- Genetic problem
20
Q
What is hypoxia?
A
Reduce amount of oxygen in the tissue
21
Q
3 causes of hypoxia?
A
- Ischaemia
- Hypoxemia
- Decreased oxygen carrying capacity of the blood
22
Q
What is ischaemia?
Give an examples
A
Reduce blood flow. It can be arterial or venous blood flow.
Ex: a patient developed coronary arteriosclerosis.(artery that supply to the muscle of the heart). Lumen of the coronary artery reduce.reduce arterial blood flow. Therefore results ischaemia.
23
Q
Why ischaemia results from reduce venous outflow ?
A
Ex : if the venous outflow is decrease, blood will accumulate in capillaries and results in decrease in arterial outflow as well.
24
Q
What is hypoxemia?
A
Reduce amount of oxygen in blood .
25
How hypoxemia occurs?
PiO2-pressure of oxygen in inspired air
PAO2- pressure of oxygen in alveolar
PaO2- pressure of oxygen in blood
SaO2- pressure of xylem in haemoglobin
Hypoxemia is PaO2 and SaO2 reduced
26
Causes of hypoxemia?
1. Decreased inspired air- high altitude,
2. Hypoventilation- accumulation of carbon dioxide- decreased PaO2
3. Ventilation defect- respiratory distress syndrome-lack of surfactant- collapse of the distal airways- no sufficient gas exchange
4. Perfusion defect- lung does not have sufficient blood supply
27
Decreased oxygen carrying capacity of the blood causes?
1. Anaemia- reduce amount of haemoglobin
2. Increased breakdown of RBC- haemolysis disease
3. Sequestration of RBC in spleen.
28
Mechanism of cell injury
1. ATP depletion
2. mitochondrial damage- leakage of proapoptotic molecule
3. Ca2+ entry- increased mitochondria permeability and activating some enzymes
4. Reactive oxygen species- damage lipid, protein, DNA
5. Membrane damage- cell membrane, lysosomal membrane
6. Misfolded protein and DNA damage
29
ATP depletion
Common cause of cell injury was hypoxia due to ischaemia. In hypoxia, due to lack of oxygen, ETC cannot function properly, therefore reduce amount of ATP
Reduce ATP
1. Anaerobic respiration (glycolysis)-lactic acid produce- lower the pH and causes chromatin clumping
2. Problem in different pumps. Ex: Na-K Atpase pump disfunction and cause cell swelling, ER swelling, loss of microvilli
3. Detachment of ribosome- reduce amount of protein synthesis
30
Mitochondrial damage
In the inner membrane, ATP are generated via ETC and oxidative phosphorylation. Whenever mitochondrial damage
1. ATP production get reduce,
2. Formation of Mitochondria Permeability Transition Pore- permeability of mitochondria membrane increase abnormally, and membrane potential is lost and wont be able to produce ATP
3. when mitochondria is damage , protein presents between inner and outer membrane of mitochondria they may leak out of mitochondria and come to the cytosol and stimulates certain enzymes and that can results in apoptosis.
31
How Increase cytosolic calcium happened?
To prevent cell injury calcium level in the cytosol is kept extremely low i.e less than 0.1 micromol compare to 1.3 millimol level of calcium outside the cells. The calcium levels inside the cells is kept low by sequestering calcium inside the mitochondria and ER .
When cell is injured, those calcium inside the mitochondria and ER get released. And also when the cell get severely injured there is pump failure and calcium from outside get inside the cells ( influx of calcium)
32
What are the results of increase of cytosolic calcium levels?
1. Increase Mitochondrial Permeability Transition Pore and results in cell injury.
2. Activating different types of enzymes
33
What are the different types of enzymes that are activated when calcium level inside the cells increased?
1. ATPase
2. Phospholipase
3. Protease
4. Endonuclease
34
What cause the mitochondrial damage?
1. Increase cytosolic calcium level.
2. R.O.S
3. Hypoxia
35
what is Reactive oxygen species?
It is oxygen derived free radicals
36
What is free radicals? And its characteristics.
Special type of molecule that has an unpaired molecule on their outer orbit.
They are very active and unstable.
They can be autocatalytic which willl results in chain reaction
37
5 Causes of free radicals generation
1. The normal oxidation and reduction reaction of normal metabolism.
Eg: partial reduction of oxygen : superoxide anion O2-, H2O2, OH-
2. Absorption of radiant energy
3. Rapid burst of ROS during inflammation
4. Metabolism of exogenous chemicals or drugs CCl4-> CCl3
5. Transition metals: iron and copper can produce free radicals
38
Antioxidants vitamins
A, C, E
39
Antioxidants for superoxide anion?
Superoxide dis u tase
40
Antioxidant for hydrogen peroxide?
Catalase
41
Antioxidant for OH-?
Glutathione peroxidase
42
What is Fenton reaction?
H2O2 + Fe 2+ -> Fe3+ + OH + OH-
All iron in our body exist in ferric form, so the ferric had to be converted to ferrous by superoxide anion.
43
Mechanism of cell injury by free radicals
They can oxidase
1. Lipids oxidation
2. Proteins oxidation
3. DNA damage
44
Common cause of membrane damage ??
1. Hypoxia
2. Increase calcium in cytosol - activated certain enzymes- protease and phospholipase
3. Bacterial toxin
4. Viral protein
5. Lyric component
6. ROS
45
Cell injury via misfolded protein and DNA damage.
Abnormal folding of protein cannot function properly
Mutation in DNA
46
What is reversible cell injury?
If an injured cells can return to the normalcy after the injurious agent or stimuli is removed it is known as reversible cell injury.
47
What is irreversible cell injury?
If the injury is extensive or persistent, the injured cells may not returned to the normalcy after the removal of the injurious stimuli and eventually the cel will die, it is known as irreversible cell injury.
48
What is the Point of no return?
The point when a cell was a reversibly damage and now become irreversibly damage and will die.
This point is still uncertain.
49
Hallmark of reversible cell injury?
1. Cellular swelling
2. Fatty change- presence of some lipids particle of cytoplasm. This is seen in cells that are either involved in fat metabolism or dependent on fat metabolism. Eg- liver hepatocytes and cardiac myocardium.
50
Morphology of reversible cell injury?
Very difficult to see
1. Pale appearance
2. Swelling
3. Weight of organ will be increased
51
Ultra structural finding of reversible cell injury?
1. Mitochondrial swelling
2. Presence of amorphous substance on the mitochondria
3. ER swelling
5. nuclear change
52
Two phenomenon of irreversible cell injury
1. Inability to reverse mitochondria damage
| 2. Profound disfunction in membrane
53
Types of irreversible cell injury?
1. Necrosis
| 2. Apoptosis
54
What is necrosis?
Spectrum of morphological changes that follow cell death in living tissue due to progressive degradative action of enzymes on lethally injured cell.
55
What is autolysis??
If the enzymes responsible for necrosis derived from damage cells itself then it is known autolysis.
56
What is heterolysis?
When the enzymes that responsible for necrosis come from inflammatory cells which came to the site of injury to give protection it Is known as heterolysis
57
Morphology of necrosis?
CYTOPLASMIC FINDING
1. Increase eosinophilia in cytoplasm because there is denaturation of protein and eosin can bind strongly to those denaturated protein.
2. Moth-eaten appearance of cytoplasm : enzymatic degradation which cause the formation of vacuoles inside the cells of cytoplasm .
3. Glassy and homogenous appearance of cytoplasm .
NUCLEAR FINDING
1. Nuclear material of cells become shrink and condense into a basophillic pyknotic mass.
2. Karyorrhexis- fragmentation of the pyknotic nucleus
3. Karyolysis- nucleus fades away
58
Types of necrosis?
1. Coagulation necrosis
2. Liquifactive necrosis
3. Gangrenous necrosis
4. Caseous necrosis
5. Fat necrosis
6. Fibrinoid necrosis
59
What is coagulation necrosis?
In this type of necrosis, cells are death but the outline and the architecture of the cells are preserves at least for few days. The reasons are the main Cause of cell injury via denaturation of protein. During the denaturation of protein not only the structural protein getting denaturated but also different enzymes. So, no enzymes remains to digest the cells. So the outline are preserved.
60
Example of coagulative necrosis?
Eg : ischaemia injury in all organs except brain will results in coagulative necrosis.
61
What is liquefaction necrosis?
Here the cells are get severely damage not by denaturation of protein but by enzymatic degradation which digest the entire area and make it liquid.
62
Example of liquefactive necrosis ?
Eg: abscess
hypoxemia in brain. The microglial cells in brain contain lots of enzymes.
63
What is gangrenous necrosis?
Gangrenous terms is usually used mainly for lower limb when there is decrease of blood supply in the lower limb.
Sometimes there is bacterial infection superimposed on the gangrenous necrosis.
Normally gangrenous necrosis is a coagulative necrosis but when there is bacterial infection superimposed, the harmful agent released by the bacteria and the enzymes that is released by the inflammatory cells that came to help the effected part, all this thing results in the liquefactive part.
64
What is wet gangrene?
When there is liquefactive necrosis we call it wet gangrene.
65
What is caseous gangrene?
Caseous means cheese like.
The name case from the fact that this type of necrosis there is white friable area. Caseous necrosis is usually seen in tuberculosis.
66
where is fat necrosis found? explain
Acute pancreatitis
Pancreases contains lipase but the lipase is not released inside the pancrease. via the pancreatic duct they go to the intestine and help in fat digestion.
When there is acute pancreatitis those lipase get released inside the pancrease or around the pancrease and it results in fat necrosis.
Sometimes the lipase they breakdown triglycerides into fatty acid and when calcium binds to fatty acid it results into fat saponification and results is chalky white appearance of those area.
67
What is fibrinoid necrosis?
Fibrinoid means like fibrin
It is usually seen in blood vessel during some immunological diseases. Antigen and antibody complexes get deposited in the blood vessels and results in cell injury and then the fibrin leaks out of the blood vessels and it gives out the pink appearance of the surrounding of blood vessels under H&E stain as there is fibrin deposition.
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