Cell Death Flashcards
1
Q
The morphologic hallmark of cell death is ______, which occurs via:
______
______
_______
A
loss of the nucleus
Nuclear condensation (pyknosis)
*Fragmentation (karyorrhexis)
*Dissolution (karyolysis),
2
Q
The two mechanisms of cell death are _________ and _____
A
NECROSIS and APOPTOSIS.
3
Q
NECROSIS
-is the death of groups of cells, often accompanied by _____
A
an inflammatory infiltrate
4
Q
Necrosis is Due to _______ process
A
some underlying pathologic
5
Q
Necrosis can be physiologic
T/F
A
F
6
Q
Necrosis is Divided into several types based on gross features
GROSS PATTERNS OF NECROSIS
List all 6
A
coagulative necrosis
-Liquefactive necrosis
-Caseous necrosis
-Gangrenous necrosis
-Fat necrosis
-Fibrinoid necrosis
7
Q
In Coagulative Necrosis
There is preservation of the _____
A
structural outline of dead cells
8
Q
In coagulative necrosis, the Necrotic tissue remains firm cell shape and organ structure are preserved by ________ , but the _____ disappears
A
coagulation of proteins
nucleus
9
Q
Coagulative necrosis is Characteristic of ischemic infarction of any organ except the _____.
A
brain
10
Q
In Coagulative necrosis, Area of infarcted tissue is often ____-shaped (pointing to ______) and ___.
A
wedge
focus of vascular occlusion
pale
11
Q
Liquefative Necrosis
-necrotic degradation of tissue that (softens or hardens?) and becomes ____.
A
Softens
liquefied
12
Q
Mechanism of Liquefative Necrosis
It is caused by the release of ______ by necrotic cells and/or the release of ______ by ______ entering the tissue.
A
lysosomal enzymes
hydrolytic enzymes
Neutrophils
13
Q
Examples of where Liquefative Necrosis occurs
________ infarction
__________
_______
A
Central nervous system
Abscess in a bacterial infection
Pancreatitis of the pancreas parenchyma
14
Q
Caseous Necrosis
-variant of _____ necrosis
-__cellular, ——-like (caseous) material is present on gross examination
-(hard or Soft?) and ___ necrotic tissue with “_______-like” appearance
-Combination of _____ and _____ necrosis
A
coagulation
A
cheese
Soft
friable
cottage cheese
coagulative and liquefactive
15
Q
Caseous Necrosis
Characteristic of granulomatous inflammation due to ———- or ____infection
A
tuberculous or fungal
16
Q
Gangrenous Necrosis
- ______ necrosis that resembles _____ tissue (dry gangrene)
-If ________ occurs, then _____ necrosis ensues (wet gangrene)
A
Coagulative
mummified
superimposed infection of dead tissues
liquefactive
17
Q
Dry Gangrene is Characteristic of ischemia of______ and ____
A
lower limb and GI tract
18
Q
Fat Necrosis
-Necrotic adipose tissue with _____ appearance due to deposition of _____
-Characteristic of trauma to fat (e.g., breast) and _____-mediated damage of ____ fat
A
chalky-white
calcium
pancreatitis
peripancreatic
19
Q
In Fat necrosis
_______ released by trauma (e.g., to breast) or _____ [e.g., pancreatitis) join with calcium via a process called ____.
A
Fatty acids
lipase
saponification
20
Q
Fibrinoid Necrosis
-Necrotic damage to _____
A
blood vessel wall
21
Q
In Fibrinoid Necrosis
Leaking of proteins (including fibrin) into vessel wall results in _______ staining of the wall microscopically
-Characteristic of malignant ____ and ______
A
bright pink
hypertension
Vasculitis
22
Q
APOPTOSIS
-programmed, _____-mediated cell death
-Examples include:
*_______ during menstrual cycle
*Removal of cells during _____
*CD8 + T cell-mediated killing of _____
A
enzyme
Endometrial shedding
embryogenesis
virally infected cells
23
Q
Apoptosis is not Energy (ATP)-dependent
T/F
A
F
It is
24
Q
Morphology of APOPTOSIS
-Dying cell ____, leading cytoplasm to become more ____
-Nucleus _____ (____) and _____ (_____).
-Apoptotic bodies fall from the cell and are removed by ______
A
shrinks
eosinophilic
condenses; pyknosis
Fragments; karyorrhexis
macrophages
25
apoptosis is not followed by inflammation
T/F
T
26
Mention the ways of Activation of caspases
1)__________ pathway
2)________ pathway
3)__________ pathway
Intrinsic mitochondrial
Extrinsic receptor-ligand
Cytotoxic CD8+ Tcell-mediated
27
Activation of caspases
1) Intrinsic mitochondrial pathway
-Cellular injury, DNA damage, or loss of hormonal stimulation leads to activation of ___ which leads to ________ which leads to ________
p53
inactivation of BCL-2
activation of BAX/BAK genes
28
BCL-2 is ________ gene
antiapoptotic
29
BAX/BAK genes are ______ genes
apoptotic
30
Activation of caspases
In Intrinsic mitochondrial pathway
Lack of BCL-2 allows _____ to leak from the _______ into the cytoplasm and activate caspases.-capsases activate enzymes like _____ and _____
cytochrome c
mitochondrial matrix
proteases and endonucleases
31
Activation of caspases
Extrinsic receptor-ligand pathway
-____ ligand binds _____ receptor (____) on the target cell, activating caspases (e.g., negative selection of thymocytes in thymus).
OR
-__________ binds ____ receptor on the target cell, activating caspases.
FAS
FAS death
CD95
Tumor necrosis factor (TNF)
TNF
32
Activation of caspases
Cytotoxic CD8+ Tcell-mediated pathway
- _____ secreted by CD8+ T cell creates _______ of target cell,
-_______ from CD8+ T cell enters ____ and activates caspases.
Perforins
pores in membrane
Granzyme
pores
33
CD8+ T cell is responsible for killing of ______ cells
virally infected
34
(T/F) The major types of necrosis are
16. Fibrinoid necrosis
17. Liquefactive necrosis
18. Caseous necrosis
19. Gangrenous necrosis
20. Fat necrosis
T
T
T
T
T
35
(T/F) Apoptosis in health can be seen in
21. Autoreactive response of T cells
22. Involution of gonads
23. Irradiation
24. During embryogenesis
25. Cytotoxic anticancer drugs
T
T
T
T
T
36
Apoptosis may be physiologic
T/F
T
37
Necrosis results from ____ of intracellular _____ and ________ of the irreversibly injured cell.
denaturation; proteins
enzymatic digestion
38
In necrosis
The enzymes are released from the dying cell’s ______ as well as the _____ of ___________
lysosomes
lysosomes
adjacent white blood cells.
39
In necrosis
The dying cell loses its membrane integrity and cellular contents spill
into surrounding tissues causing ______.
• These changes may take _____ to be morphologically visible, however,
certain chemicals released from the injured cell may be ________ e.g. M.I. & cardiac specific enzymes
inflammation
hours
detectable in
body fluids
40
Morphology in necrosis
•Increased ______ (the ___ colour of the cytoplasm). This is due to _______ which binds _________.
•Increased _______ appearance due to the loss of ________.
•_______ cytoplasm due to ________ cytoplasmic organelles.
•Myelin figures: from dead cell or organellar membranes. The myelin
figures may be ______ by ______ or degraded into _______ which may become ________ leading to the
_________
eosinophilia; pink; loss of cytoplasmic RNA; hematoxylin
glassy; glycogen particles
Vacuolated; enzyme digested
phagocytosed; other cells; fatty acids; calcified; calcification of dead cells
41
Steps of nuclear changes:
Karyolysis: _____ chromatin resulting from loss of ____ as a result of enzymatic degradation by ______
Pyknosis: nuclear _____ and increased _______. Also seen in ______
Karyorrhexis: ________ of the nucleus
Fading; DNA; endonucleases
Shrinkage; basophilia; apoptosis
Fragmentation
42
1.Coagulative necrosis
2.Liquefactive necrosis e.g. ____
3.Gangrenous necrosis e.g. _______
4.Caseous necrosis e.g. ____
5.Fat necrosis e.g. _______,_____
6.Fibrinoid necrosis e.g. ______
C.N.S.
Foot gangrene
TB
pancreatitis, breast
blood vessels
43
Coagulative necrosis
•Affected tissue are ( loose or firm?) because the injury denatures the ____ and prevents _____ of dead cells..
•The dead cell is eventually _____ by ______ or digestion from _____ enzymes
Firm; enzymes; proteolysis
cleared; phagocytosis; leukocytic
44
Most common type of necrosis is ______
Coagulative
45
An area of localised coagulative necrosis is called an _____.
infarct
46
Coagulative necrosis
•Microscopically, the cells retain their outlines, however the ______ and ______ are lost (‘ ______/_____ appearance).
The affected cells are ______ and more ______ than usual.
cytoplasmic and nuclear details
Tombstone’/’Ghost’
swollen; eosinophilic
47
In coagulative necrosis, microspically, the cells retain their outlines
T/F
T
48
In Liquefactive necrosis
•Also caused by ischaemic injury, bacterial/fungal infections. Microbes
stimulate the accumulation of _____ and subsequent release of _____ enzymes
•The cellular hydrolytic enzymes play a dominant role in the digestion of the affected cells creating _____ material.
•Examples are ______(CVA/”stroke”) and ______ cavities.
leukocytes
Cellular hydrolytic ; semi-fluid
brain infarcts
abscess (pus)
49
In Gangrenous necrosis
Commonly used in clinical practice.
•Usually results from _______ on a tissue
which has _________ ( ________ necrosis).
The bacterial infection leads to (more or less?) ______ necrosis (_______). Why?
•
Examples: __________, ________
superimposed bacterial infection
lost its blood supply
coagulative necrosis
More ; liquefactive
Wet gangrene
diabetic foot gangrene; frostbite gangrene
50
In caseous necrosis
_____-like
•Characteristically found in _____ infections.
Morphology:
•Grossly: ( soft or hard?) , (amorphous or granular?), _____ color .
Cheese; Tuberculous
Soft ; granular; yellowish
51
In caseous necrosis
Morphology:
Microscopically: characteristic ______ (____ cells, ______ cells and peripheral cuff of ______) with ____ area of necrosis
granuloma
Epithelioid
Giant
lymphocytes
Central
52
In Fat necrosis
•Refers to focal areas of ____
•Pancreatitis: release of _____ from pancreatic _____ cells liquefy the
_______ of adipocytes in the _____. The released fatty acids can combine with ____ to form areas of ______ (______ visible areas)
fat destruction.
lipases; acinar cells; membranes; peritoneum
calcium; saponification
chalk-white
53
Fat necrosis is a clinical term
T/F
T
54
In Fat necrosis
•
Traumatic fat necrosis (breast): seen with loss of ______ to breast adipose tissue resulting in the death of the adipocytes and their digestion by
________. May mimic a _______.
blood supply
macrophages
carcinoma
55
Fibrinoid necrosis
Seen in immune reactions involving ______
blood vessels.
56
In fibrinoid necrosis
Deposition of ____ complexes on the _________ leading to activation of immune reactions against the wall components. E.g. is ____________ with ________.
Ab-Ag (Antibody- Antigen)
blood vessel walls
eosinophilic granulomatosis
polyangitis
57
Apoptosis is __________
Literally _____
programmed cell death.
suicide
58
Apoptosis
May be physiologic e.g.
• ______
• Involution of hormone dependent tissues after hormone withdrawal e.g. shedding of ______, reduction in _____ at the end of ______
• Involution of the _____ at an early age
• Elimination of ______ lymphocytes either before or after maturation to prevent damage to body tissues
• Death of cells which have served their function e.g. _______ after inflammation.
Embryogenesis
endometrial lining
breast size; breast feeding
thymus
self-reactive
leukocytes
59
The absence of necessary stimulatory signals induces ______
apoptosis
60
Apoptosis
Pathologic conditions:
• DNA damage via _____ etc. Damaged DNA may lead to _____
• Accumulation of misfolded proteins leads to _______ which results in activation of apoptosis
• Certain viral infections e.g. Adenovirus, HIV. Cytotoxic T-lymphocytes which are
specific for viral infected cells induce apoptosis in these cells. There may be
significant resulting tissue damage.
• Obstruction of ducts in parenchymal organs e.g. _____,_____
radiation; carcinogenesis
ER stress
salivary glands, pancreas.
61
Morphological changes in apoptosis
1. Cell _____
2. _____ condensation under the nuclear membrane. The nucleus may be ____.
3.Formation of cytoplasmic ____ and ___
4. _________ of apoptotic bodies
shrinkage
Chromatin; fragmented
blebs; apoptotic bodies
Phagocytosis
62
Mechanism of apoptosis
Central is the activation of ____
• There are two steps in apoptosis:
•________ phase
•_______ phase
• There are two pathways in apoptosis
•_______ (_______) pathway
• ________ (________) pathway
caspases
Initiation; Execution
Intrinsic; mitochondrial
Extrinsic; death receptor-mediated
63
There are two steps in apoptosis:
• Initiation phase: _______ become _____
• Execution phase:_____ trigger the ______ of cellular components
Caspases ; active
Caspases
degradation
64
Intrinsic pathway: Anti and Pro apoptotic proteins
These are proteins which _______ or _______ the process of apoptosis in the cell.
•The concentration of these proteins is tightly regulated by the cell.
•In a viable cell, ______s lead to production of anti-apoptotic proteins e.g. BCL2, BCL-XL, MCL1. Anti-apoptotic proteins maintain the _____ of the _____ thus preventing leakage of apoptosis inducing proteins e.g. _____
promote or antagonise
growth factor
integrity; mitochondrial membrane
cytochrome c.
65
Intrinsic pathway: Anti and Pro apoptotic proteins
However when a cell is injured or deprived of survival signals, _______ proteins are inhibited while _____ proteins (e.g. BAX, BAK) are activated.
Pro-apoptotic proteins create a channel in the __________ leading to leakage of
________ from the ________ which activates the caspases.
anti-apoptotic
pro-apoptotic
outer mitochondrial membrane
cytochrome c
membranous space
66
Sensors:___-only proteins e.g.___,___, BIM, Puma. They sense ____ levels and regulate ___________ proteins
BH3
BAD, BID
cellular stress
anti-&prp-apoptotic
67
Intrinsic Pathway( initiation phase)
• Also known as the ______ pathway because of the key role of the _____ in the process.
• Cell injury results in permeability of the _________ release of pro-apoptotic proteins such as _____ . This results in
activation of _______ leading to the onset of apoptosis.
Mitochondrial; mitochondria
mitochondrial membrane
cytochrome c
caspase 9
68
_________ is the major mechanism for apoptosis in all mammalian cells.
Intrinsic Pathway
69
Extrinsic pathway( initiation phase)
Also called the ________ pathway.
Activated following binding to the ______ on the plasma membrane and they have a ______ domain ( ____ domain) which delivers apoptotic signals that activate ________.
• This mechanism is seen in ________ cell activity (kills virus infected and tumour cells) as well as on ___-cells that recognise self-antigens (eliminate self-reactive lymphocytes).
death receptor-mediated
death receptors
cytoplasmic; death
caspase 8
cytotoxic T-
T
70
The extrinsic pathway initiation phase
This pathway can be inhibited by a protein called _____ (produced by
certain viruses e.g. _______ and _____)
FLIP
Herpes virus and normal cells
71
Execution phase
Both the intrinsic and extrinsic initiator pathways converge on the
same execution phase.
•
Activated caspase-8 (extrinsic pathway) and caspase 9 (intrinsic
pathway) now activate caspases 3 & 6.
•
Activated caspases 3 & 6:
•
Activate DNAase which cleaves DNA
•
Degrade structural components of the nuclear matrix leading to nuclear
fragmentation
B
72
Both the intrinsic and extrinsic initiator pathways converge on the same execution phase.
T/F
T
73
Execution phase
Activated ______ (extrinsic pathway) and _______ (intrinsic pathway) now activate _________ which does 2 things:
1)Activate ______ which cleaves ____
2)Degrade structural components of the _______ leading to ______
caspase-8; caspase 9
caspases 3 & 6
DNAase; DNA
nuclear matrix
nuclear fragmentation
74
Overview of biochemical features of apoptosis
1. Activation of caspases: Caspases exist as _______. Functionally divided into 2: initiator (____) and executioner (____).
2.DNA & protein breakdown – this involves the action of ____ and ____ endonucleases which cleave DNA.
3.Membrane ______ and recognition by ________ – the plasma membrane phospholipid orientation changes so that it is easily recognized by phagocytes. These phospholipids are easily recognized by ______ staining (immunohistochemistry)
inactive proenzymes; 8 , 9; 3 , 6
Ca and Mg
alteration; phagocytes
Annexin V
75
______ activity is the basis for detection of cell death by cytochemical techniqies
Endonuclease
76
CPC correlations: examples of apoptosis
1. Deprivation of ______: e.g. hormones, antigens (lymphocytes), nerve growth factor (nerves). Occurs via the _____ pathway
2.DNA damage: this causes accumulation of ___ protein which in cases of excessive damage activates the _____ pathway of apoptosis.
3.Protein ____: Seen in _____ diseases e.g.
Alzheimer’s, cystic fibrosis, Alpha1 antitrypsin disease. These proteins accumulate in the cytosol and lead to apoptosis.
growth factors; intrinsic
p53; intrinsic
misfolding; neurodegenerative
77
In the absence of p53 (________ syndrome), accumulation of damaged DNA may lead to _______
Li Fraumeni
cancer
78
More examples of apoptosis
4. Extrinsic pathway (___): ____ on T cells bind ___ on neighboring lymphocytes leading to destruction of T lymphocytes that _______
• 5. Cytotoxic T-lymphocytes: recognise foreign ___ on the surface of
infected cells. The T-cells secrete _____ which forms _____ in the membrane of the infected cells. The T-cell now secretes _____ through the pores into the affected cell which activate ———.
Fas/FasL
FasL; Fas; recognize self-antigen.
Ag; perforin; pores ; granzymes
caspases
79
Dysregulated apoptosis
1) Defective apoptosis and increased cell survival.
a.In cells with _____ mutation, there is accumulation of damaged DNA which leads to cancer.
b.When self reactive lymphocytes are not eliminated, they may cause ______
2.Increased apoptosis and excessive cell death
a. ______ diseases e.g. Alzheimer’s, Parkinsons.
b.Death of ______ cells
c. ______ diseases (myocardial infarction
TP53; autoimmune disorders
Neurodegenerative
virus infected
Ischaemic
80
Necroptosis
Resembles both necrosis and apoptosis
•Sometimes called _______
•(does or Does not?) involve caspase activation
•Examples: Steatohepatitis, acute __\\\, back-up defense for _______ microbes e.g. CMV
programmed necrosis
Does NOT
pancreatitis
apoptosis evading
81
Autophagy
Cell eats ______
its own contents.
82
Differences between Necrosis and apoptosis
Cells size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation
Swelling; shrinkage
Pyknosis,karyorrhexis,karyolysis ;Fragmentation into nucleosome-size fragments
Disrupted; intact(orientation of lipids is altered tho)
Enzymatic digestion so it may leak out
of cell; Intact , it may be released in
apoptotic bodies
Frequent; NO
83
Differences between Necrosis and apoptosis
Physiologic or pathologic role?
Invariably pathologic (culmination
of irreversible cell injury)
Often physiologic, means of
eliminating unwanted cells; may
be pathologic after some forms of
cell injury, especially DNA damage
84
Apoptosis eliminates cells that are injured beyond repair (with or without?) eliciting a host reaction
Without
85
The presence of _____ is therefore a marker for cells undergoing apoptosis
active caspases
86
Autophagy involves sequestration of cellular organelles into
cytoplasmic ________(_____) that fuse
with ______ and digest enclosed material.
Autophagic vacuoles
Autophagosomes
lysosomes
87
Autophagy is an adaptive response that is enhanced during _______, allowing the cell to _______ to survive.
nutrient deprivation
cannibalize itself
88
Dysregulation of autophagy occurs in many disease states,including cancer, inflammatory bowel diseases, and neurodegenerative disorders.
T/F
T
89
Autophagy plays a role in host defense
against certain microbes.
T/F
T
90
Too much ROS is known as ____
Oxidative stress
91
______ is responsible for cell death in a living body
Autolysis
92
Cell death caused by autolysis is produced by _______
Endogenous enzymes
93
Liquefaction in liquefactive necrosis of the brain is mediated by _______ cells
Liquefaction in liquefactive necrosis in an abscess is mediated by _______ cells
Microglial cells
Neutrophils
