4 Cell injury, aging, and death Flashcards
(74 cards)
1
Q
tissue hypoxia
A
- lack of oxygen
- causes power failure in cell
- often caused by ischemia
- may be caused by heart failure, lung disease, RBC disorders
2
Q
ischemia
A
- disrupts blood supply to a tissue> allows metab wastes to accumulate + deprives cell of nutrients for glycolysis>lactic acidosis
- most common cause of cell injury
- chronic sublethal ischemia usually results in atrophy
- injures cells faster than hypoxia alone
- results in think skin, muscle wasting, hair loss
- can be due to chronic nutrient starvation
3
Q
why does hypoxia cause cell injury
A
oxygen is needed to make ATP
4
Q
how does hypoxia work
A
1 lack of O means no ATP produced
2 w/o ATP, waste accumulates inside cell
3 w/o ATP, Na cannot pump out of cell
4 accumulation of Na in cell, causes water to move in
5 accumulation of Na causes hydropic swelling, which cause 0 protein synth
5
Q
3 ways cells respond to environmental changes or injury
A
1 reversible cell injury
2 adaptation
3 apoptosis/necrosis
6
Q
reversible cell injury
A
when change is mild or short lived, the cell may withstand assault + return to normal
7
Q
which cell response to change/injury is reversible and irreversible?
A
reversible cell injury + adaptation are reversible.
cell death aka apoptosis or necrosis are irreversible
8
Q
reversible cell injury
A
- results in cell swelling + accumulation of excess substances in cell
- changes affect dysfunction in ATP, normal metab functions, or metab enzymes
-once acute stress is removed, the cell returns to its preinjury state
9
Q
hydropic swelling aka oncosis
A
- accumulation of water in cell
- usually due to malfunction in Na-K pumps which is dependent on ATP
- characterized by large pale cytoplasm, dilates E.R., + swole mitochondria
10
Q
intracellular accumulations categories
A
1 excessive amt of normal intracellular substances like fat
2 accum of abnormal substances produced by cell bc faulty metab or synth
3 accum of pigments/particles that cell is unable to degrade
11
Q
normal intracellular substances that tend to accumulate
A
lipid, glycogen, carb, proteins
12
Q
accum of fat/lipid in liver is associated w…
A
excessive intake of alcohol
13
Q
2 ways the cell limits accum of abnormal intracellular protein
A
1 chaperone proteins attempt to refold abnormal proteins into its correct shape
2 ubiquitin-proteasome system that digest targeted proteins into fragments
14
Q
atrophy
A
when cells shrink and reduce their differentiated functions in response to a variety of normal and injurious factors
15
Q
6 general causes of atrophy
A
1 disuse 2 denervation 3 ischemia 4 nutrient starvation 5 interruption of endocrine signals 6 persistent cell injury
16
Q
common form of atrophy that is a result from reduction of functional deman
A
disuse atrophy
ex) immobilization fr bed rest or casting. on resumption of activity, the tissue returns to its normal size
17
Q
atrophy that results fr persistent cell injury is most commonly related to…
A
chronic inflammation + infection
18
Q
2 pathways for protein degradation
A
1 ubiquitin-proteasome systm (degrades to small fragments) 2 autophagy (lysosomes fuse w intracellular structures leading to hydrolytic degradation of components)
19
Q
hypertrophy
A
increase in cell mass accompanies by an augmented functional capacity
- response to increased physiologic or pathophysiologic demands
- subsides when increased demand is removed but may not return to normal
20
Q
cellular enlargements results primarily from…
A
a net increase in cellular proteins content
21
Q
organ enlargement may result of…
A
hypertrophy (increase in cell size) and hyperplasia (increase in cell number)
22
Q
examples of hypertrophy and hyperplasia in muscle cells
A
hypertrophy- increase in skeletal muscle mass fr exercise
hyperplasia - division of satellite cells (muscle stem cells)
23
Q
example of physiologic hypertrophy
A
breast + uterus due to trophic hormones
24
Q
hyperplasia
A
increase in number of cells
- cells that are capable of mitotis division generally increase their functional capacity
- may also result fr persistent cell injury
25
an increase in RBC in response to high altitude or liver enlargement in response to drug detox are examples of
demand-induced hyperplasia
26
increase in division of endometrial/uterine cells in response to estrogen is an example of...
trophic hormone induced hyperplasia
27
dysregulation of hormones or growth factors can result in...
pathologic hyperplasia
ex thyroid or prostate enlargement
28
examples of hyperplasia due to chronic irritation of epithelial cells
corns + calluses
29
metaplasia
replacement of one differentiated cell type w another
-most often occurs as adaptation to persistent injury w replacement of cell type that can better tolerate injurious stimulation
- fully reversible when injurious stimuli is removed
- may become cancerous
30
5 types of adaptive cellular response
```
1 atrophy (shrink)
2 hypertrophy (enlargen)
3 hyperplasia (inc in number)
4 metaplasia (conversion of one cell type to another)
5 dysplasia (disorderly growth)
```
31
common cell type conversion in metaplasia
glandular epithelium to squamous epithelium
32
dysplasia
disorganized appearance of cells bc of abnormal variations in size, shape, + arrangement
- occurs more frequently in hyperplastic squamous epithelium
- may occur in intestinal mucosa
- significant pot'l to become cancerous; usually regarded as preneoplastic lesions
33
carcinoma in situ
severe dysplasia that involves entire thickness of epithelium
34
necrosis vs apoptosis
- both are irreversible cell injury
- necrosis is usually cell rupture. spilling of contents into ECF, + inflammation; due to ischemia or toxic injury
- apoptosis usually dont rupture, usually ingested w minimal disruption w/o inflammation; due to injury that doesnt directly kill but triggers intracellular cascades that activate cell suicide, requires adequate ATP
35
morphological changes in necrotic cells
- pyknotic (shrunken nucleus)
- karyolysis (degraded nucleus)
- swollen cell vol
- dispersed ribosome
- disrupted plasma + organelle membranes
36
critical event in necrosis cell death
disruption of permeability barrier of plasma membrane
37
manifestations that indicate necrosis
- inflammation
- malaise
- fever
- inc heart rate
- inc WBC count
- loss of appetite
38
presence of specific cellular proteins in the blood is used as an indicator of...
the location + extent of necrosis cell death
ex) inc in amylase in serum indicates pancreatic damage
ex) inc in kinase or cardiac troponin indicates myocardial damage
39
4 types of tissue necrosis
1 coagulative
2 liquefactive
3 fat
4 caseous
*they differ primarily in type of tissue affected
40
which type of tissue necrosis is most common?
coagulative necrosis
41
cascading manifestations of coagulative necrosis
*manifestations of coagulative necrosis are the same regardless of the cause of cell death
1 ischemic cellular injury
2 loss of plasma membrane's ability to maintain electrochem gradients
3 influx of Ca ions + mitochondrial dysfunctions
4 degradation of plasma membranes + nuclear structures
42
coagulative necrosis
- area of coagulative necrosis is composed of denatures proteins + is relatively solid
- then slowly dissolved by proteolytic enzymes
- general tissue architecture is preserved for long time (weeks) (unlike liquefactive necrosis)
43
liquefactive necrosis
- dissolution of dead cells occurs v quickly
- a liquefied area of lysosomal enzymes + dissolved tissue nay result to form an abscess or cyst
- may be seen in brain (rich in degradative enzymes + little supportive tissue)
- may result fr bacterial infections that triggers localized collection of WBC (phagocytic WBC contain potent degradative enzymes that digest dead cells + produce liquid debris)
44
fat necrosis
death of adipose tissue
| -usually results fr trauma or pancreatitis
45
fat necrosis process
1 release of activated digestive enzymes fr pancreas or injured tissue
2 enzymes attack cell membrane of fat cells, cause release of stored triglycerides
3 pancreatic lipase can hydrolyze the triglycerides to free fatty acids + glycerol, which precipitate as Ca soaps
-fat necrosis appears as chalky white area of tissue
46
caseous necrosis
characteristic of lung tissue damaged by tuberculosis
- area of dead lung tissue are white, solf, fragile resembling clumpy cheese
- dead cells are walled off fr rest of lung tissue by inflammatory WBC
- in center, dead cells lose their cellular structure but are not totally degraded
- necrotic may persist indefinitely
47
gangrene
term used to describe cell death involving large area of tissue
-usually results fr interruption of major blood supply to body part
48
types of gangrene and their type of necrosis
dry gangrene is coagulative necrosis
wet gangrene is liquefactive necrosis
gas gangrene infection of necrotic tissue by clostridium
49
in contrast to necrosis, apoptosis is...
tidy and does not elicit inflammation.
| it is usually a normal physiologic process that regulate normal system function
50
necrosis and apoptosis portion of tissue death after a myocardial infarction (heart attack)
20% necrosis
| 80% apoptosis
51
when the rate of apoptosis is ___ than the rate of cell replacement, tissue/organ function may be impaired
GREATER
52
EXTRINSIC SIGNALS that cause apoptosis
- may be triggered by withdrawal of "survival" signals that normally suppress apoptotic pathways
- -if contacts/signals are removed, cell death cascade is activated
- extracellular signals (like Fas ligand) that bind to the cell + trigger the death cascade thru activation of death receptors
53
P53
protein that governs an INTRINSIC apoptosis pathway
- TUMOR SUPPRESSOR GENE
- normally low amt but inc in response to severe cellular DNA damage
- high levels cause apoptosis
54
caspases
family of enzymes that are the main components of proteolytic cascade that degrades key intracellular structures leading to cell death.
-proenzymes that are activated in a cascade
55
```
type of tissue necrosis for each organ:
1 heart
2 brain
3 lung
4 pancreas
```
1 heart -COAGULATIVE
2 brain -LIQUEFACTIVE
3 lung -CASEOUS
4 pancreas -FAT
56
anaerobic respiration
- due to hypoxia
- pyruvate end products fr glycolysis are converted into LACTATE
- lactate released in bloodstream results in LACTIC ACIDOSIS
- as pH falls, cellular proteins + enzymes become more dysfunctional
57
reperfusion injury
most cellular damage occurs after the blood supply to tissues has been restored
58
3 components of ischemia-reperfusion
1 Ca overload fr blood
2 formation of free radicals
3 subsequent inflammation
59
free radicals
reactive O molecules bc of unpaired electrons on outer orbital
- they steal H atoms + form abnormal bonds
- damage cell membrane, denature proteins, disrupt cell chromosomes
ex superoxide (O2 -), peroxide (H2O2), hydroxyl radicals (OH-)
60
why can't ischemic cells tolerate Ca overflow?
depleted ATP means they are unable to control ion flux across the cell membrane
-accumulation of Ca may trigger apoptosis or activate enzymes that degrade lipids in the membrane
61
when is ischemic injury nonreversible?
cell death occurs when plasma, mitochondrial, + lysosomal membranes are critically damaged.
62
what causes cell injury via nutrient deficiency?
- poor intake
- altered absorption
- impaired distribution by circulatory systm
- inefficient cellular uptake
63
what causes cell injury via nutrient excess?
BMI > 27kg/m2: health risk
| BMI > 30kg/m2: obesity
64
infectious + immunologic cell injury
DIRECT: bacteria/virus itself cause virus
INDIRECT: added injury may occur indirectly by triggering body's immune response
65
examples of DIRECT infectious/immunologic cell injury
- clostridium perfrinogens produce enzymes that eat meat and cause gangrene
- microbes that secrete exotoxins + attack nervous system
- endotoxins are in gram neg like e.coli
66
chem injury
-toxic chem or poisons can cause cellular injury both DIRECTLY or by BECOMING METABOLIZED INTO REACTIVE CHEMS by the body
67
physical/mechanical injury
- extreme temp
- abrupt changes in atmospheric pressure
- mech deformation
- electricity
- IONIZING RADIATION (breaks chem bonds)
68
extreme temp cell injury
COLD: vasoconstriction, less flow due to inc viscosity
HEAT: vasodilation, more flow due to dec in viscosity (more fluid)
69
mechanisms of radiation-induced injury
- heat
- radiolysis
- free radicals
70
order of radiation-induced injury
radiant energy either cause
1a direct hit on DNA
2a DNA damage that causes
3a genetic mutations + apoptosis
or 1b ionization (which can also caught DNA damage)
2b free radical damage cell structure
3 acute cell destruction + necrosis
71
first manifestation of most form of reversible cell injury....
hydropic swelling
72
any injury that results in loss of ATP will also result in...
hydropic swelling
73
intracellular accumulation that leads to cellular injury
- toxicity
- immune response
- taking up cellular space
74
fas ligand
binds to receptors to activate caspase and apoptosis
