Cell Injury And Death Flashcards
(65 cards)
1
Q
Cell injury
A
-it is damage to a cell when a stimuli is so severe that it can’t adapt or adaptations fail
2
Q
Types of injury and outcome
A
- reversible : when stimuli is removed cell reverts to normal
- non-reversible : cell will not recover from damage after injurious agent is removed. Cell undergoes death by necrosis or apoptosis
3
Q
Causes of cell injury
A
1 hypoxia 2 chemical agent 3 physical agents 4 nutritional Imbalance 5 infection 6 immunological causes 7 genetics
4
Q
Causes of hypoxia
A
1 ischemia - reduced blood glue to tissue
2 reduced O2 carrying capacity of blood
3 hypoxemia - reduced O2 in blood
5
Q
List Mechanisms of cell injury
A
1 reduced ATP synthesis
2 reactive oxygen species
3 membrane damage
4 Ca2+ influx
6
Q
Causes of reduced ATP synthesis
A
- hypoxia ( via ischemia )
- membrane damage via Ca2+ which activates membrane degrading enzymes
- via ROS which react with and degrade membrane
7
Q
Effects of reduced ATP synthesis
A
1 Na+/K+ pump no energy to function
- influx of Na and H20 follows sodium , efflux of K+
- cell and ER swelling
- loss of microvilli
2 Increase in anaerobic glycolysis
- reduced glycogen
- increased lactic acid increase pH
- enzymes denatured due to infra pH
- chromatin clumps due to increased pH
3 ribosomes detachment
- reduced protein synthesis
- lipid deposition
8
Q
Use of Na/K pumps
A
Maintain electrolytes balance between cell and extra cellular fluid
9
Q
What causes increase of Ca2+ in a cell
A
1 membrane damage to mito ( via H2O2 ) forms permeability transition pores which release stored Ca2+ into cyto
- reduced function and no ATP for pumps ( via ischemia and peroxide )
2 membrane damage to ER releases stored Ca2+
10
Q
Effects of efflux of Ca2+
A
1 activates enzymes which degrade cell components
- phospholipase degrade membrane lipids
- endonucleases cleave DNA
- protease degrade proteins
- ATPase degrade ATP
11
Q
What causes membrane damage
A
- reactive oxygen species
- enzymes activated by Ca2+
12
Q
Effects of membrane damage
A
1 on mitochondria- reduced ATP synthesis
- permeability transition pores releases Ca2+ into cyto
- mito releases death factors into cyto
2 on lysosome membrane - release digestive enzymes into cyto
3 on plasma - leakage of cellular contents
-loss of osmotic and ionic balance between cell and ecm
13
Q
What causes influx of Free radicals ( reactive O2 species )
A
- transition metals ( Fe and Cu ) can initiate generation of ROS
- produced during normal cell process ( absorption of radiant energy , reduction reactions in metabolism , metabolism of drugs )
14
Q
Effects of free radicals
A
- react with and degrade cellular membranes
- oxidative modification of proteins ( damage active sites and enhance degradation )
- cause lesions on DNA via ds and ss breaks
15
Q
Why are free radicals so reactive
A
-due to unpaired electron in outer shell. Can easily accept or donate electrons
16
Q
How does the body fight against oxidative stress
A
- antioxidants ( deactivate already formed oxidants or prevent formation of them )
- enzymes from peroxisomes degrade them eg glutathione peroxide
- metal transport proteins bind to transition metals and reduce formation of oxidants eg ferritin
17
Q
Microscopic view of reversible damage
A
- cell swelling
- cyto organelles filled with fluid and swelling
- blebb formation
- loss of microvilli
- accumulation of myelin figures
- fatty change
18
Q
What is fatty change and myelin figures and cause
A
- fatty change occurs due to abnormal accumulation of TRIGS In cell from fat stores
- myelin figures are lipid masses from membrane broken down into FA and TRIGs. Can be calcified and form calcium salts
19
Q
Outcome of irreversible damage
A
Death of cell via
1 Necrosis
2 Apoptosis
20
Q
What is Necrosis
A
-Mechanism of cell death in living tissue and always caused by pathological conditions
21
Q
Common causes of necrosis
A
1 ischemia
2 pathogens ( viral , bacterial )
3 toxins
4 inflammation
22
Q
Major outcome of necrosis and significance
A
Plasma membrane is disrupted and cellular contents leak out leading to acute inflammation by the body in the site of necrosis
this response is essential to lay the foundation of healing process
23
Q
When are Morphological changes due to necrosis visible
A
1 not visible immediately ( 1-3 hours )
24
Q
Describe the change in nucleus in necrosis
A
1 starts as normal cell
2 chromatin clumps and nucleus shrinks into pyknotic body
3 karyorrhexis occurs. ( breaking of pyknotic body into smaller fragments )
4 karyolysis occurs ( fragments completely digested by endonucleases )
25
Cytoplasmic changes due to necrosis
1 deeply eosinophilic with H and E stain due to denatured proteins which bind with eosin
2 loss of glycogen particles makes cyto appear homogenous
3 appearance of myelin figures
4 cytoplasm becomes vaculated
5 discontinuous plasma and organelle membrane
6 calcification of FA into chalky deposits
7 membrane blebs
8 disintegration of ER
26
Removal of necrostic tissue and where prominent
```
1 autolysis ( synthesis cells leak enzymes )
2 heterolysis ( done by macrophages)
```
27
2 Types of necrotic tissue and the others
```
1 coagulative
2 liquifactive
3 fat
4 caseous
5 gangrene
6 fibrinoid
```
28
Coagulative necrosis cause ( via removal ) and microscopic appearance
Digestion by autolysis is insufficient so proper digestion occurs but heterolysis
-dead cells have visible outline
29
Common causes and victims of coagulative and major characteristics
- hypoxia and heat
- solid organs ( heart, liver, kidney )
- stages of nuclear digestion visible
30
Mechanism of coagulative
- hypoxia leads to increased anaerobic glycolysis
- increase lactic acid
- denature enzymes
- cell can’t eat itself ( poor autolysis )
-heat denatures proteins
31
What is infarction and causes
- death due to obstruction of blood flow to organ due to rupture, blocking or constriction of blood vessels.
- lead to hypoxia
32
What is ischemia
-reduced blood flow to organ or tissue
33
Macroscopic observations of coagulative
- initial several days looks normal
- area appears mottled ( spotty ) due to seepage of blood from ruptured blood vessels
- blood clears and area looks firm and pale
- area lined by rim of hyperemia in surrounding viable tissue
- area looks hemorrhagic especially
34
What is hemorrhage and hyperemia and causes
- blood loss from circulatory system through internal or external rupture of vessels
- excess blood in tissue due to acute inflammation
35
Hemorrhagic necrosis description and where found
-special type of coagulative where area looks like it’s bleeding Especially at tissue with dual blood supply ( lung infarction or at congested tissue ( torsion of testis ) )
36
Liquefactive necrosis 2 major causes and where prominent
- tissue undergoes autolysis
- where suppurative inflammation takes place via pyogenic bacterial infection
-In lysosome rich tissue
37
Liquefactive due to autolysis where seen and causes
-seen in brain infarction me and acute pancreatitis due to high level of digestive enzymes they make or from glial cells
38
Contributing factors to liquid necrosis in brain
- lack of collagen CT
| - lipid rich content
39
What is suppurative inflammation
This is inflammation where the bodies neutrophil rich exudate fight pyogenic bacteria And there is formation of pus
40
Liquefaction due to heterolysis
-where there is severe bacterial infection and acute suppurative inflammation occurs
41
What is exudate
-mass of cells which seep out of blood vessels
42
Macroscopic and microscopic of liquefactive necrosis
-area is soft and pulp like and has a liquid consistency
- can’t identify outline of dead cells
- numerous neutrophil in pus
43
What is pus description and formation
Has a creamy yellow green color at center surrounded by pyogenic membrane
-formed when neutrophils phagocytize pyogenic bacteria both dying creating it
44
Caseous necrosis description, where prominent , cause and reason for consistency it has
- type of coagulative necrosis, consistency like cottage cheese characterized by yellow crumbling nature of necrotic tissue
- occurs in infection with mycobacterium tuberculosis
- significant tissue damage during bacteria killing
- Consistency do to release of my colic acid from cell wall of mycobacterium
45
Where does fat necrosis occur and types
-at adipose tissue
```
1 enzymatic fat n
2 traumatic ( non-enzymatic fat n )
```
46
Enzymatic fat n where occurs, what happens and what is seen
Seen in acute pancreatitis or other pancreatic injuries at mesenteric and retroperitoneal adipose tissue
- injury to pancreas causing release of phospholipase and lipase into surrounding tissue by assignor cells
- membranes broken into FA wc fuse with Ca and form chalky deposits of calcium salts
47
Traumatic fat n where seen, what happens and what is seen
- seen in high lipid content tissue
- adipose disrupted due to trauma release TAG broken into FA fuse with Ca and chalky white deposits
-undigested TAG form lipid pool and some engulfed by macrophages which fuse and form giant touton bodies surrounding pools
48
Effect of touton bodies and lipid pools
-xanthogranulomatous inflammation - chronic inflammation associated with lipid macrophage collections
49
Fibrinoid necrosis where seen , what happens and what is seen
Seen in immune reactions involving blood vessels
- Characterized by deposition of immune complexes and fibrin
- gives rise to bright pink stain with H and E stain
50
What are immune complexes, where does the fibrin come from and what is an antigen
Antigens + antibodies
- seeps from blood vessels
- foreign pathogen stimulating immune response in body especially release of antibodies
51
Gangrene characteristics and types
- Area of the dead tissue in living person characterized by black discoloration
- wet
- dry
52
Wet gangrene cause, what Is seen cause of black discoloration and bacterial growth
- Area infected by putrefactive and anaerobic bacteria
- Very low oxygen in the tissue facilitates anaerobic bacteria growth
- foul smell due to nitrogenous compounds
- black color due to sulphur deposition
53
Where does wet gangrene develops
-places where anaerobic bacteria could access and should have low O2
54
What does the bacteria of wet gangrene do and treatment
- invades viable tissue and causes septicemia
| - removal of infected body part mandatory
55
When and where is wet common common
- lower limbs of diabetic patients
- after extensive injury eg warfare
- neglected bed sores
- necrosis of intestines due to hernia or vovulus
56
Gas gangrene cause and where seen and characteristics
- type of wet gangrene caused by clostridia organism eg clostridium per-fringes
- seen in deep soft tissue and muscle
- increased production of gas gives rise to crackling sound when pressed
- area black
-common in septic abortions, snake bites and use of black tar heroin from
57
Dry gangrene cause and characteristics
No superadded infection ie no anaerobic bacteria due to O2 presence
- develops due to gradual death tissue supplied with end arteries subjected to low grade long term ischemia
- tissue falls of and no spreading
58
Clinical manifestation of necrosis
- of epithelium : ulcers
- myocardium infarction : heart failure
- cerebral infarction : stroke , neurological defects
- local effects : pain and edema
- acute tubular necrosis of kidney : renal failure
59
What is apoptosis and causes
-physiological cell death which is controlled by gene coded proteins
1 normal organ development
2 to Maintain tissue turnover
3 hormones induced ( involution of mamory glands after breast feeding
4 following cell cycle arrest
60
2 pathways of apoptosis
```
1 intrinsic ( mitochondrial )
2 extrinsic
```
61
What is caspase what they do and types and they functions
- protease which kill the cell by degrading cellular protein
- 8-10 are initiatory caspase ( activate executory caspase )
- 3,6,7 are executory caspase ( they are the ones which degrade cellular protein )
62
How do cells prevent apoptosis
-they receive survival signals which stimulate production of Bcl-2 and Bcl-x ( proteins that prevent leakage of cytochrome c )
63
Mitochondrial pathway
-DNA damage or lack of survival signals or cell cycle arrest will activate stress sensors ( BH3 proteins ) which
1 block anti-apoptosis proteins
2 bind with membrane and create Channels for release of cytochrome c
64
How does cytochrome c initiate death
-it binds with Apaf-1 forming apoptosome which activates initiation caspase and these actively execution caspase
65
Extrinsic pathway
Death signal comes from outside of cell
-cell has trans membrane receptors ( Fas ) to bind to signal ligands ( FasL ) on surface of T cells
-3 more Fas receptors bind together and their cytoplasmic death domains form binding site for adapter called Fadd causing formation of initiator
-active execution
/apoptosis
