Cell injury, death & adaptation Flashcards
1
Q
4 mechanisms of adaptation to reversible injury / stress
A
Hypertrophy, Hyperplasia, Atrophy, Metaplasia
2
Q
Cellular injury resulting from decreased oxygen
A
Ischemia
3
Q
Molecule with unpaired electron in outer orbit
Highly reactive
A
Free radical
4
Q
Highly reactive molecules which contain oxygen atoms
A
Reactive oxygen species
5
Q
ROS are produced normally during these 2 processes
A
Cellular respiration
Leukocytes during inflammation (respiratory burst)
6
Q
During the red-ox reactions of mitochondrial respiration, sequential reduction of O2 to H2O2 can result in the occasional “lost” electron, which can form this
A
Superoxide
Lost e- is added to oxygen to form O2-
7
Q
Enzyme that forms superoxide radical from oxygen atom
A
Phagocyte/NADPH oxidase
8
Q
Enzyme that forms hydrogen peroxide from superoxide radical
A
Superoxide dismutase
9
Q
Enzyme that forms hypochlorite from hydrogen peroxide
A
Myeloperoxidase
10
Q
What is the Fenton reaction?
A
Hydrogen peroxide is converted to OH- (hydroxyl) in the presence of Fe2+
11
Q
Hydrogen peroxide is converted to hydroxyl OH- in the presence of this
A
Transition metals (Cu and Fe)
12
Q
2 ions whose cytosolic levels increase during membrane damage
A
Ca2+ and Na+
13
Q
Increased phospholipid degradation may occur when phosphatases are activated by increase cytosolic levels of this
A
Calcium
14
Q
Lysosome membrane damage can result in these 2 things
A
Autolysis and/or necrosis
15
Q
Glycolytic and citric acid cycle enzymes are found in this part of the mitochondria
A
Core
16
Q
Respiratory chain enzymes are found in this part of the mitochondria
A
Inner membrane
17
Q
ATP generation occurs in this part of the mitochondria
A
Intermembrane space
18
Q
Porin proteins selectively permit small molecules to pass and are found in this part of the mitochondria
A
Outer membrane
19
Q
Increased cytosolic calcium leads to this
A
Enzyme activation
Phospholipidases cause membrane damage
Proteases degrade structural proteins and others
20
Q
2 mechanisms of mitochondrial damage
A
Increased cytosolic calcium leads to enzyme activation (phospholipidases, proteases)
Lack of oxygen results in ROS
21
Q
ATP depletion as a result of mitochondrial damage leads to apoptosis or necrosis?
A
Necrosis
22
Q
Decreased oxidative phosphorylation as a result of mitochondrial damage leads to this
A
Increased glycolysis, increased lactic acid, protein dysfunction
23
Q
Leakage of mitochondrial proteins like cytochrome C during mitochondria damage leads to this
A
Apoptosis
24
Q
Leakage of cytochrome C into cytosol signals cell damage, and activates this
A
Caspase enzyme pathway
(DNase activation, protease activation, programmed cell death)
25
This activates the caspase enzyme pathway during mitochondrial damage
Leakage of cytochrome C into cytosol
26
Incomplete oxidative phosphorylation during mitochondrial damage produces these
Free radicals
27
DNA damage is often repaired with this pathway
p53 pathway
28
During the p53 pathway of DNA damage repair, the cell cycle is arrested in this phase
G1
29
What happens if the p53 pathway of DNA damage repair is unsuccesful?
Apoptosis occurs; mediated through bcl-2/Bax/Bak pathway
30
Are normal cytosolic levels of calcium high or low?
Very low due to pumps and membranes
31
Disturbance of calcium homeostasis has these 2 effects
Influx into mitochondria (swelling, decreased ATP generation)
Inappropriate enzyme activation (endonucleases, proteases, phospholipases, ATPase)
32
3 intracellular accumulations that are signs of damage/degeneration
Water, Fat, Lipofuscin
33
2 extracellular accumulations that are signs of damage/degeneration
Hyaline material, Calcium deposition
34
Accumulation of intracellular lipid
Sign of reversible injury
Occurs mostly in cells involved in lipid metabolism (liver)
Steatosis
35
Lipid is _______ so it does not dissolve in cytoplasm
Hydrophobic
36
Excess lipid is morphologically seen as these
Droplets
37
What produces vacuolization of cytoplasm?
Excess lipid, which is hydrophobic and does not dissolve in cytoplasm, so instead is seen as droplets
38
Golden-brown intracellular indigestible material made of lipid and protein
“Wear and tear” pigment
Gradually accumulates as cells age
Mostly seen in post-mitotic cells (liver, heart, neurons)
Lipofuscin
39
What is lipofuscin?
Golden-brown intracellular indigestible material made of lipid and protein
40
Lipofuscin is mostly seen in this type of cell
Post-mitotic cells (liver, heart, neurons)
41
Any material that appears dense, amorphous, and intensely eosinophilic
Also intracellular amorphous pink deposits
Hyaline
42
Vascular hyaline may be due to long-term ______
Hypertension
43
What is hyaline?
Any material that appears dense, amorphous, and intensely eosinophilic
44
Damaged proteins deposited in the kidney glomerulus in diabetes
Hyaline
45
Calcium deposits may form in these two pathological categories
Dystrophic calcification
Metastatic calcification
46
Category of pathological calcium deposition:
Calcium deposits in abnormal tissue, usually necrotic
Dystrophic calcification
47
Category of pathological calcium deposition:
Calcium precipitates in tissues due to abnormally high serum concentrations
Metastatic calcification
48
Occurs when cell swells due to increased cytoplasmic water content
H2O mostly in ER cisternae
Number of organelles does not increase, just water content
Morphology shows lighter staining
Occurs due to decreased ability to maintain ion concentrations, especially Na+
Hydropic swelling
49
Morphology of hydropic swelling will appear this color of staining
Lighter staining / pale
50
When Na/K ATPase is dysfunctional, it fails to pump Na ____ of cell
Out
51
What causes hydropic swelling?
Decreased ability to maintain ion concentrations (leakiness, pump failure)
52
Is hydropic swelling a sign of reversible or irreversible injury?
Reversible
If injury ceases (O supply restored, toxin removed, nutrients given), ATPase function is restored and water balance is restored
53
Cellular adaptation involving increased cell size
E.g. muscle cell increases number of contractile elements
Hypertrophy
54
Define hypertrophy
Cellular adaptation involving Increased cell size
55
Cellular adaptation involving increased cell number
E.g. high altitude living leads to increased number of RBCs
Hyperplasia
56
Define hyperplasia
Cellular adaptation involving increased cell number
57
Chronic skin disorder characterized by the presence of hard, extremely itchy bumps known as nodules
Example of hyperplasia
Prurigo Nodularis (Picker's nodule)
58
Cellular adaptation involving decreased cell size and/or function
E.g. uterine muscle shrinks after pregnancy
Atrophy
59
Define atrophy
Cellular adaptation involving decreased cell size and/or function
60
Uterine muscle shrinking after pregnancy is this kind of cellular adaptation
Atrophy
61
Cellular adaptation involving a change in cell type; change of one phenotype of another as a response to irritation/stress
New cell type is more able to handle stress
Metaplasia
62
Metaplasia example:
Squamous epithelium changes to this if increased acid is present in esophagus
Glandular epithelium
63
Metaplasia example:
Glandular epithelium changes to this in bronchus after prolonged exposure to smoke
Squamous epithelium
This change can lead to squamous cancer in the lungs
64
Type of cell death that induces cell fragmentation which elicits inflammatory response (WBCs)
Necrosis
65
Necrosis is cell death which induces cell _______ which elicits inflammatory response (WBCs)
Cell fragmentation
66
Class form of necrosis due to ischemia (aka infarction)
All tissues except CNS undergo this type when infarcted
Lack of blood supply and delayed ability to dissolve cell
Coagulative necrosis
67
All tissues except ____ will undergo coagulative necrosis when infarcted
CNS
68
Type of necrosis where morphological cell outlines remain intact for a period
Nucleus is absent or faint/eosinophilic
Coagulative necrosis
69
Morphology of nucleus in coagulative necrosis
Nucleus is absent or faint/eosinophilic
70
Type of necrosis that occurs when rate of dissolution greatly exceeds rate of repair
Dead tissue becomes digested by proteolytic enzymes
Typical necrosis in bacterial infections (e.g. abscess), results in viscous yellow fluid (pus)
Also seen in CNS infarction
Liquefactive necrosis
71
When does coagulative necrosis occur?
All tissues except CNS will undergo coagulative necrosis when infarcted
72
When does liquefactive necrosis occur?
Occurs when rate of dissolution greatly exceeds rate of repair
73
Viscous yellow fluid (pus) is distinctive of this type of necrosis
Liquefactive necrosis
74
Typical necrosis in bacterial infections (e.g. abscess)
Liquefactive necrosis
75
Liquefactive necrosis is typical in this type of infection
Bacterial infections (e.g. abscess)
76
Type of necrosis involving ischemic necrosis of several tissue planes
Gangrenous necrosis
77
Common sites of gangrenous necrosis
Limb/digit, Penile, Bowel
78
When does gangrenous necrosis occur?
Ischemic necrosis of several tissue planes
79
Type of gangrenous necrosis involving loss of blood supply resulting in dried tissue planes
Dry gangrene
80
Type of gangrenous necrosis involving superimposed bacterial infection resulting in liquefaction
Wet gangrene
81
Type of necrosis where cells are fragmented resulting in particulate, crumbly appearance
Tuberculosis is typical example
Caseous necrosis
82
Tuberculosis involves this type of necrosis
Caseous necrosis
83
In tuberculosis, the center of the granuloma is filled with this
Caseous necrosis
84
In tuberculosis, caseous necrosis is surrounded by this
Granulomatous inflammation (macrophages, giant cells, fibrotic wall)
85
What is characteristic of caseous necrosis?
Necrotic cells are fragmented resulting in particulate, crumbly appearance
86
Type of necrosis involving enzymatic digestion of lipid resulting in saponification
Typical example is pancreatitis
Fat necrosis
87
What is fat necrosis?
enzymatic digestion of lipid resulting in saponification
88
Condition which releases pancreatic lipase and is an example of fat necrosis
Pancreatitis
89
Pancreatitis is an example of this type of necrosis
Fat necrosis
90
Pancreatic lipase is normally in this intracellular location
Membrane bound vesicles
Cellular damage releases lipase, which digests peripancreatic fat. Triglycerides are digested to release fatty acids, which combine with calcium and form insoluble calcium salts.
91
In fat necrosis in pancreatitis, cellular damage releases lipase from membrane bound vesicles. It then digests peripancreatic fat, and triglycerides are digested to release fatty acids.
These fatty acids then combine with an ion to form these
Combine with calcium to form insoluble calcium salts
92
Morphology of fat necrosis
Fat lobules become white and firm
Saponified fat does not dissolve in processing (remains on histology slide)
93
Type of necrosis of vascular wall resulting in leakage of plasma proteins
These deposit in wall and is seen in certain types of vasculitis
Fibrinoid necrosis
94
What is fibrinoid necrosis?
Necrosis of vascular wall resulting in leakage of plasma proteins
95
Type of necrosis seen in certain types of vasculitis
Fibrinoid necrosis
96
Morphology of apoptotic cells
Cell shrinks (dense eosinophilic cytoplasm)
Chromatin condenses at periphery
Nucleus fragments and form apoptotic bodies (phagocytes apoptotic bodies but no inflammation)
97
2 pathways of apoptosis
Mitochondrial and extrinsic
98
Cytochrome C is released into the cytoplasm during mitochondrial damage, and then binds to and activates this
Caspase 9
pathway to apoptotic death
99
Caspase 9 is activated by this
Cytochrome c (which is released into the cytoplasm during mitochondrial damage)
100
Mitochondrial pathway of apoptosis is inhibited by this
Bcl2 protein
101
Bcl2 protein inhibits this
Mitochondrial pathway of apoptosis
102
Apoptosis pathway involving the release of cytochrome C into cytoplasm, which binds and activates caspase 9
Mitochondrial
103
Apoptosis pathway where molecules bind death receptors on cell surface, leading to caspase 8 activation
Extrinsic
104
During the extrinsic pathway of apoptosis, molecules bind death receptors on cell surface and activate this
Caspase 8
105
Fas binds Fas ligand, leading to apoptotic death of auto-reactive T cells, is an example of this apoptosis pathway
Extrinsic
106
Apoptosis enzyme activated in the extrinsic pathway
Caspase 8
107
Apoptosis enzyme activated in the mitochondrial pathway
Caspase 9
108
Caspase 8 is activated in this apoptosis pathway
Extrinsic
109
Caspase 9 is activated in this apoptosis pathway
Mitochondrial
110
Both apoptosis pathways (mitochondrial and extrinsic) converge as a common execution phase pathway with these 3 effects
Nucleus dissolved via DNAases
Cytoplasmic blebs --> apoptotic bodies
Apoptotic bodies removed by phagocytes
111
Pro-apoptotic forces in healthy cells that are inhibited by growth factor signaling (bcl) mediators
BAX and BAK
112
Levels of BAX, BAK, and bcl-2 in healthy cells
Pro-apoptotic forces (BAX and BAK) inhibited by growth factor signaling (bcl) mediators
113
Levels of BAX, BAK, and bcl-2 in cells with lack of pro-growth signaling
Balance shifted to BAX/BAK; increased release of BAX/BAK
Decreased bcl-2
114
Increased release of BAX/BAK during intrinsic apoptosis form this
Form membrane channels in mitochondria, leading to release of cytochrome C
115
BAX/BAK form membrane channels in mitochondrion, releasing this
cytochrome C
116
Process by which a cell digests parts of itself
Used in states of deprivation
Cell constituents delivered to lysosomes --> autophagosome
Recycles nutrients, organelles, etc.
Defective/dysregulation in various disease states (neoplasia, neurodegenerative diseases)
Autophagy
117
In autophagy, cell constituents are delivered to these
Lysosomes --> autophagosome
118
This process is defective/dysregulation in various disease states such as neoplasia and neurodegenerative diseases
Autophagy
