NBME PATHOLOGY EXAM 2025
QUESTIONS AND ANSWERS
Apoptosis: - ANS 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? - ANS 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? - ANS 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withdrawn from a proliferating cell population.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? - ANS BAX and BAK
are pro. Bcl-2 is anti-apoptotic.
How does Bcl-2 function? - ANS It prevents cyt c release by binding to an inhibiting Apaf-1,
which normally INDUCES caspases.
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,What happens if Bcl-2 is overexpressed? - ANS 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? - ANS 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? - ANS 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? - ANS After it crosslinks with FasL, multiple Fas molecules
coalesce. This makes a binding site for a death domain.
Necrosis: - ANS 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: - ANS 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: - ANS 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: - ANS TB, systemic fungi, Nocardia. Tissue maintains a cheese-like
appearance. Tissue is a proteinaceous dead cell mass.
Fatty necrosis: - ANS Enzymatic--Pancreas. Saponification. Released fatty acids interact with
calcium to form soaps. Calc deposits appear dark on staining. Nonenzymatic--breast trauma.
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, Fibroid necrosis: - ANS Occurs in blood vessels. Henoch-Schonlein purpura, Churg-Strauss
syndrome. Malignant hypertension. Accumulation of amorphous, basic proteinaceous
substances resembling fibrin.
Gangrenous necrosis: - ANS Dry (ischemic coagulative) and wet (infection). Common in limbs
and GI tract.
Reversible cell injury with O2: - ANS 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: - ANS nuclear pyknosis, karyolysis and karyorrhexis. Ca2+ influx-->
caspase activation. PM damage. lysosomal rupture. mitochondrial permeability.
Areas of the brain susceptible to ischemia: - ANS 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: - ANS Subendocardium (LV)
Areas of kidney: - ANS Straight segment of the proximal tubule (medulla) and thick ascending
loop (medulla).
Areas of liver: - ANS Area around central vein (zone III)
Areas of colon: - ANS splenish flexure, colon
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QUESTIONS AND ANSWERS
Apoptosis: - ANS 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? - ANS 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? - ANS 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? - ANS BAX and BAK
are pro. Bcl-2 is anti-apoptotic.
How does Bcl-2 function? - ANS It prevents cyt c release by binding to an inhibiting Apaf-1,
which normally INDUCES caspases.
COPYRIGHT © 2025 BRAINBARTER ALL RIGHTS RESERVED 1
,What happens if Bcl-2 is overexpressed? - ANS 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? - ANS 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? - ANS 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? - ANS After it crosslinks with FasL, multiple Fas molecules
coalesce. This makes a binding site for a death domain.
Necrosis: - ANS 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: - ANS 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: - ANS 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: - ANS TB, systemic fungi, Nocardia. Tissue maintains a cheese-like
appearance. Tissue is a proteinaceous dead cell mass.
Fatty necrosis: - ANS Enzymatic--Pancreas. Saponification. Released fatty acids interact with
calcium to form soaps. Calc deposits appear dark on staining. Nonenzymatic--breast trauma.
COPYRIGHT © 2025 BRAINBARTER ALL RIGHTS RESERVED 2
, Fibroid necrosis: - ANS Occurs in blood vessels. Henoch-Schonlein purpura, Churg-Strauss
syndrome. Malignant hypertension. Accumulation of amorphous, basic proteinaceous
substances resembling fibrin.
Gangrenous necrosis: - ANS Dry (ischemic coagulative) and wet (infection). Common in limbs
and GI tract.
Reversible cell injury with O2: - ANS 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: - ANS nuclear pyknosis, karyolysis and karyorrhexis. Ca2+ influx-->
caspase activation. PM damage. lysosomal rupture. mitochondrial permeability.
Areas of the brain susceptible to ischemia: - ANS 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: - ANS Subendocardium (LV)
Areas of kidney: - ANS Straight segment of the proximal tubule (medulla) and thick ascending
loop (medulla).
Areas of liver: - ANS Area around central vein (zone III)
Areas of colon: - ANS splenish flexure, colon
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