,Apoptosis: - CORRECT ANSWERS-Programmed cell death. REQUIRES ATP. Can
occur via the intrinsic or extrinsic pathways, both of which involve activation of cytosolic
caspases which mediate cellular breakdown. ***Unlike necrosis, apoptosis does not
involve significant inflammation. Involves eosinophilic cytoplasm, cell shrinkage,
pyknosis and basophilia, membrane blebbing and karyorrhexis, and formation of
apoptotic bodies which are phagocytosed. **DNA laddering is a sensitive indicator of
apoptosis** Occurs because during karyorrhexis endonucleases yield 180bp fragments.
Radiation therapy does what? - CORRECT ANSWERS-Causes apoptosis of cancer
cells because it causes formation of free radicals which lead to dsDNA breakage.
rapidly dividing cells like skin and GI mucosa are highly susceptible to radiation-induced
apoptosis.
Intrinsic pathway of apoptosis: what is its general purpose / when does it occur? -
CORRECT ANSWERS-It's involved in tissue remodeling in embryogenesis. Often
occurs when a regulating factor is withdrawn from a proliferating cell population. For
example, low IL-2 after completion of an immunological reaction causes apoptosis of
proliferating effector cells. Also occurs in response to injury from radiation, toxins,
hypoxia,etc. Changes in proportions of pro- and anti-apoptotic factors leads to an
increase in mitochondrial permeability and cyt c release.
BAK, BAX, Bcl-2: Which of these are pro- and which are anti-apoptotic? - CORRECT
ANSWERS-BAX and BAK are pro. Bcl-2 is anti-apoptotic.
How does Bcl-2 function? - CORRECT ANSWERS-It prevents cyt c release by binding
to an inhibiting Apaf-1, which normally INDUCES caspases.
What happens if Bcl-2 is overexpressed? - CORRECT ANSWERS-This occurs in
follicular lymphoma. Apaf-1 is over-inhibited which leads to tumorigenesis because of
lowered caspase activation.
Extrinsic pathway of apoptosis: 2 basic pathways? - CORRECT ANSWERS-1. Ligand
receptor interactions. FasL binding to Fas (CD95). 2. Immune cell-->cytotoxic T-cell
release of perforin and granzyme B.
Where is Fas-FasL interaction required? - CORRECT ANSWERS-In thymic medullary
negative selection. Mutations in Fas increases the numbers of circulating self-reactive
lymphocytes due to failure of clonal deletion. **Defective fas-fasL interactions is the
basis of autoimmune disorders**
How does Fas initiate cell death? - CORRECT ANSWERS-After it crosslinks with FasL,
multiple Fas molecules coalesce. This makes a binding site for a death domain.
, Necrosis: - CORRECT ANSWERS-Exogenous injury causes enzymatic degradation
and protein denaturation of a cell. IC components extravasate. **There's an
inflammatory process unlike apoptosis**
Coagulative necrosis occurs in the: - CORRECT ANSWERS-Caused by ischemia or
infarction typically. heart, liver, kidney. Occurs in tissues supplied by end arteries. High
cytoplasmic binding of acidophilic dye. Proteins denature first followed by enzymatic
degradation.
Liquefactive necrosis occurs in the: - CORRECT ANSWERS-brain, bacterial abscess
and pleural effusion. Occurs in CNS because of high fat content there. Unlike coag
necrosis, enzymatic degradation due to release of lysosomal enzymes occurs first.
Caseous necrosis: - CORRECT ANSWERS-TB, systemic fungi, Nocardia. Tissue
maintains a cheese-like appearance. Tissue is a proteinaceous dead cell mass.
Fatty necrosis: - CORRECT ANSWERS-Enzymatic--Pancreas. Saponification.
Released fatty acids interact with calcium to form soaps. Calc deposits appear dark on
staining. Nonenzymatic--breast trauma.
Fibroid necrosis: - CORRECT ANSWERS-Occurs in blood vessels. Henoch-Schonlein
purpura, Churg-Strauss syndrome. Malignant hypertension. Accumulation of
amorphous, basic proteinaceous substances resembling fibrin.
Gangrenous necrosis: - CORRECT ANSWERS-Dry (ischemic coagulative) and wet
(infection). Common in limbs and GI tract.
Reversible cell injury with O2: - CORRECT ANSWERS-low ATP synthesis, cellular
swelling because with no ATP there's impaired Na/K pump. Nuclear chromatin
clumping. Low glycogen. Fatty change. Ribosomal detachment (low protein synthesis).
Irreversible cell injury: - CORRECT ANSWERS-nuclear pyknosis, karyolysis and
karyorrhexis. Ca2+ influx--> caspase activation. PM damage. lysosomal rupture.
mitochondrial permeability.
Areas of the brain susceptible to ischemia: - CORRECT ANSWERS-ACA / MCA / PCA
boundary areas. The watershed areas, or border zones, receive dual blood supply from
most distal branches of two arteries. However, systemic hypoperfusion may cause
ischemia in these areas. **Hypoxic ischemic encephalopathy affects pyramidal cells of
the hippocampus and Purkinjie cells of the cerebellum.
Areas of heart: - CORRECT ANSWERS-Subendocardium (LV)
Areas of kidney: - CORRECT ANSWERS-Straight segment of the proximal tubule
(medulla) and thick ascending loop (medulla).
occur via the intrinsic or extrinsic pathways, both of which involve activation of cytosolic
caspases which mediate cellular breakdown. ***Unlike necrosis, apoptosis does not
involve significant inflammation. Involves eosinophilic cytoplasm, cell shrinkage,
pyknosis and basophilia, membrane blebbing and karyorrhexis, and formation of
apoptotic bodies which are phagocytosed. **DNA laddering is a sensitive indicator of
apoptosis** Occurs because during karyorrhexis endonucleases yield 180bp fragments.
Radiation therapy does what? - CORRECT ANSWERS-Causes apoptosis of cancer
cells because it causes formation of free radicals which lead to dsDNA breakage.
rapidly dividing cells like skin and GI mucosa are highly susceptible to radiation-induced
apoptosis.
Intrinsic pathway of apoptosis: what is its general purpose / when does it occur? -
CORRECT ANSWERS-It's involved in tissue remodeling in embryogenesis. Often
occurs when a regulating factor is withdrawn from a proliferating cell population. For
example, low IL-2 after completion of an immunological reaction causes apoptosis of
proliferating effector cells. Also occurs in response to injury from radiation, toxins,
hypoxia,etc. Changes in proportions of pro- and anti-apoptotic factors leads to an
increase in mitochondrial permeability and cyt c release.
BAK, BAX, Bcl-2: Which of these are pro- and which are anti-apoptotic? - CORRECT
ANSWERS-BAX and BAK are pro. Bcl-2 is anti-apoptotic.
How does Bcl-2 function? - CORRECT ANSWERS-It prevents cyt c release by binding
to an inhibiting Apaf-1, which normally INDUCES caspases.
What happens if Bcl-2 is overexpressed? - CORRECT ANSWERS-This occurs in
follicular lymphoma. Apaf-1 is over-inhibited which leads to tumorigenesis because of
lowered caspase activation.
Extrinsic pathway of apoptosis: 2 basic pathways? - CORRECT ANSWERS-1. Ligand
receptor interactions. FasL binding to Fas (CD95). 2. Immune cell-->cytotoxic T-cell
release of perforin and granzyme B.
Where is Fas-FasL interaction required? - CORRECT ANSWERS-In thymic medullary
negative selection. Mutations in Fas increases the numbers of circulating self-reactive
lymphocytes due to failure of clonal deletion. **Defective fas-fasL interactions is the
basis of autoimmune disorders**
How does Fas initiate cell death? - CORRECT ANSWERS-After it crosslinks with FasL,
multiple Fas molecules coalesce. This makes a binding site for a death domain.
, Necrosis: - CORRECT ANSWERS-Exogenous injury causes enzymatic degradation
and protein denaturation of a cell. IC components extravasate. **There's an
inflammatory process unlike apoptosis**
Coagulative necrosis occurs in the: - CORRECT ANSWERS-Caused by ischemia or
infarction typically. heart, liver, kidney. Occurs in tissues supplied by end arteries. High
cytoplasmic binding of acidophilic dye. Proteins denature first followed by enzymatic
degradation.
Liquefactive necrosis occurs in the: - CORRECT ANSWERS-brain, bacterial abscess
and pleural effusion. Occurs in CNS because of high fat content there. Unlike coag
necrosis, enzymatic degradation due to release of lysosomal enzymes occurs first.
Caseous necrosis: - CORRECT ANSWERS-TB, systemic fungi, Nocardia. Tissue
maintains a cheese-like appearance. Tissue is a proteinaceous dead cell mass.
Fatty necrosis: - CORRECT ANSWERS-Enzymatic--Pancreas. Saponification.
Released fatty acids interact with calcium to form soaps. Calc deposits appear dark on
staining. Nonenzymatic--breast trauma.
Fibroid necrosis: - CORRECT ANSWERS-Occurs in blood vessels. Henoch-Schonlein
purpura, Churg-Strauss syndrome. Malignant hypertension. Accumulation of
amorphous, basic proteinaceous substances resembling fibrin.
Gangrenous necrosis: - CORRECT ANSWERS-Dry (ischemic coagulative) and wet
(infection). Common in limbs and GI tract.
Reversible cell injury with O2: - CORRECT ANSWERS-low ATP synthesis, cellular
swelling because with no ATP there's impaired Na/K pump. Nuclear chromatin
clumping. Low glycogen. Fatty change. Ribosomal detachment (low protein synthesis).
Irreversible cell injury: - CORRECT ANSWERS-nuclear pyknosis, karyolysis and
karyorrhexis. Ca2+ influx--> caspase activation. PM damage. lysosomal rupture.
mitochondrial permeability.
Areas of the brain susceptible to ischemia: - CORRECT ANSWERS-ACA / MCA / PCA
boundary areas. The watershed areas, or border zones, receive dual blood supply from
most distal branches of two arteries. However, systemic hypoperfusion may cause
ischemia in these areas. **Hypoxic ischemic encephalopathy affects pyramidal cells of
the hippocampus and Purkinjie cells of the cerebellum.
Areas of heart: - CORRECT ANSWERS-Subendocardium (LV)
Areas of kidney: - CORRECT ANSWERS-Straight segment of the proximal tubule
(medulla) and thick ascending loop (medulla).
