Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – The Genome
Stem: A newborn shows lactic acidosis and multi-organ
dysfunction shortly after birth. Genetic testing reveals a
pathogenic mutation that impairs pyruvate dehydrogenase
complex activity. Which cellular consequence best explains
the infant’s lactic acidosis?
A. Increased flux through the TCA cycle generating excess
acetyl-CoA
B. Accumulation of pyruvate with increased conversion to
lactate by lactate dehydrogenase
C. Enhanced oxidative phosphorylation with elevated ATP
production
D. Upregulation of gluconeogenesis consuming lactate
Correct Answer: B
,Rationale (correct): Pyruvate dehydrogenase deficiency blocks
conversion of pyruvate to acetyl-CoA, causing pyruvate
accumulation and increased reduction to lactate by lactate
dehydrogenase, producing lactic acidosis. This reflects a direct
metabolic consequence of an enzyme defect encoded in the
nuclear genome.
Rationale (A): Increased TCA flux would lower pyruvate levels,
not cause lactic acidosis; it is inconsistent with PDH deficiency.
Rationale (C): Oxidative phosphorylation is impaired indirectly
due to substrate shortage; ATP is not typically elevated.
Rationale (D): Gluconeogenesis consumes lactate in the Cori
cycle but is not the primary response to PDH deficiency in
neonates.
Teaching Point: PDH defects cause pyruvate buildup and lactic
acidosis via increased lactate formation.
2. Chapter Reference – The Genome
Stem: A patient’s tumor has a point mutation in a DNA
mismatch repair gene leading to microsatellite instability.
Which cellular process is most directly compromised by
this mutation?
A. Base excision repair of oxidized bases
B. Proofreading by DNA polymerase during replication
C. Post-replicative correction of mismatches between
daughter and template strands
D. Nonhomologous end joining of double-strand breaks
,Correct Answer: C
Rationale (correct): Mismatch repair proteins recognize and
correct mismatches that escape DNA polymerase proofreading
after replication; loss leads to microsatellite instability.
Rationale (A): Base excision repair handles small base lesions
(e.g., oxidized bases), not replication mismatches.
Rationale (B): Proofreading is performed by polymerase 3′→5′
exonuclease activity during replication, upstream of mismatch
repair.
Rationale (D): Nonhomologous end joining repairs double-
strand breaks, unrelated to microsatellite instability.
Teaching Point: Mismatch repair fixes replication errors; its loss
causes microsatellite instability.
3. Chapter Reference – Cellular Housekeeping
Stem: A neuron accumulates aggregated, ubiquitinated
proteins in the cytoplasm due to impaired proteasome
function. Which intracellular degradation pathway is
primarily affected?
A. Autophagy–lysosomal degradation of organelles
B. Ubiquitin–proteasome system for short-lived and
misfolded proteins
C. Endosome–plasma membrane recycling pathway
D. Mitochondrial mitophagy
Correct Answer: B
, Rationale (correct): The ubiquitin–proteasome system targets
many short-lived and misfolded proteins for proteasomal
degradation; impairment leads to ubiquitinated protein
aggregates.
Rationale (A): Autophagy-lysosomal systems handle bulk
degradation, long-lived proteins, and organelles rather than the
proteasome’s primary substrates.
Rationale (C): Endosome recycling manages membrane
proteins, not cytosolic misfolded proteins.
Rationale (D): Mitophagy specifically degrades mitochondria,
not general ubiquitinated cytosolic proteins.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded proteins; its failure causes toxic aggregates.
4. Chapter Reference – Cellular Housekeeping
Stem: A patient with α1-antitrypsin (A1AT) Z variant
accumulates A1AT polymers in hepatocyte endoplasmic
reticulum (ER). Which stress response is activated and
contributes to hepatocyte injury?
A. Unfolded protein response (UPR) leading to decreased
protein synthesis and possible apoptosis
B. Enhanced mitochondrial biogenesis to sequester
misfolded proteins
C. Increased proteasomal activity without transcriptional
changes
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – The Genome
Stem: A newborn shows lactic acidosis and multi-organ
dysfunction shortly after birth. Genetic testing reveals a
pathogenic mutation that impairs pyruvate dehydrogenase
complex activity. Which cellular consequence best explains
the infant’s lactic acidosis?
A. Increased flux through the TCA cycle generating excess
acetyl-CoA
B. Accumulation of pyruvate with increased conversion to
lactate by lactate dehydrogenase
C. Enhanced oxidative phosphorylation with elevated ATP
production
D. Upregulation of gluconeogenesis consuming lactate
Correct Answer: B
,Rationale (correct): Pyruvate dehydrogenase deficiency blocks
conversion of pyruvate to acetyl-CoA, causing pyruvate
accumulation and increased reduction to lactate by lactate
dehydrogenase, producing lactic acidosis. This reflects a direct
metabolic consequence of an enzyme defect encoded in the
nuclear genome.
Rationale (A): Increased TCA flux would lower pyruvate levels,
not cause lactic acidosis; it is inconsistent with PDH deficiency.
Rationale (C): Oxidative phosphorylation is impaired indirectly
due to substrate shortage; ATP is not typically elevated.
Rationale (D): Gluconeogenesis consumes lactate in the Cori
cycle but is not the primary response to PDH deficiency in
neonates.
Teaching Point: PDH defects cause pyruvate buildup and lactic
acidosis via increased lactate formation.
2. Chapter Reference – The Genome
Stem: A patient’s tumor has a point mutation in a DNA
mismatch repair gene leading to microsatellite instability.
Which cellular process is most directly compromised by
this mutation?
A. Base excision repair of oxidized bases
B. Proofreading by DNA polymerase during replication
C. Post-replicative correction of mismatches between
daughter and template strands
D. Nonhomologous end joining of double-strand breaks
,Correct Answer: C
Rationale (correct): Mismatch repair proteins recognize and
correct mismatches that escape DNA polymerase proofreading
after replication; loss leads to microsatellite instability.
Rationale (A): Base excision repair handles small base lesions
(e.g., oxidized bases), not replication mismatches.
Rationale (B): Proofreading is performed by polymerase 3′→5′
exonuclease activity during replication, upstream of mismatch
repair.
Rationale (D): Nonhomologous end joining repairs double-
strand breaks, unrelated to microsatellite instability.
Teaching Point: Mismatch repair fixes replication errors; its loss
causes microsatellite instability.
3. Chapter Reference – Cellular Housekeeping
Stem: A neuron accumulates aggregated, ubiquitinated
proteins in the cytoplasm due to impaired proteasome
function. Which intracellular degradation pathway is
primarily affected?
A. Autophagy–lysosomal degradation of organelles
B. Ubiquitin–proteasome system for short-lived and
misfolded proteins
C. Endosome–plasma membrane recycling pathway
D. Mitochondrial mitophagy
Correct Answer: B
, Rationale (correct): The ubiquitin–proteasome system targets
many short-lived and misfolded proteins for proteasomal
degradation; impairment leads to ubiquitinated protein
aggregates.
Rationale (A): Autophagy-lysosomal systems handle bulk
degradation, long-lived proteins, and organelles rather than the
proteasome’s primary substrates.
Rationale (C): Endosome recycling manages membrane
proteins, not cytosolic misfolded proteins.
Rationale (D): Mitophagy specifically degrades mitochondria,
not general ubiquitinated cytosolic proteins.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded proteins; its failure causes toxic aggregates.
4. Chapter Reference – Cellular Housekeeping
Stem: A patient with α1-antitrypsin (A1AT) Z variant
accumulates A1AT polymers in hepatocyte endoplasmic
reticulum (ER). Which stress response is activated and
contributes to hepatocyte injury?
A. Unfolded protein response (UPR) leading to decreased
protein synthesis and possible apoptosis
B. Enhanced mitochondrial biogenesis to sequester
misfolded proteins
C. Increased proteasomal activity without transcriptional
changes
