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 – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A newborn is found to have failure to thrive and
recurrent infections. Genetic testing reveals a nonsense
mutation in a gene encoding a protein required for V(D)J
recombination. Which mechanism most likely explains
how a nonsense mutation causes disease?
A. Gain of function via increased protein stability
B. Altered gene expression from promoter activation
C. Premature stop codon producing truncated,
nonfunctional protein
D. Increased mRNA stability leading to overproduction of
protein
Answer: C
Rationales:
, • Correct (C): Nonsense mutations introduce a premature
termination codon, producing truncated proteins that are
often nonfunctional or degraded by nonsense-mediated
decay, disrupting processes like V(D)J recombination.
• A: Gain-of-function with increased stability is more typical
of missense mutations that enhance activity, not classic
nonsense mutations.
• B: Promoter activation affects transcription initiation, not
the protein-coding sequence altered by a nonsense
mutation.
• D: Nonsense mutations typically decrease mRNA stability
via nonsense-mediated decay rather than increase it.
Teaching Point: Nonsense mutations often yield truncated
proteins or mRNA decay causing loss of function.
2. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A patient’s tumor shows microsatellite instability
(MSI). Which DNA repair pathway is most likely defective
in this tumor?
A. Homologous recombination repair
B. Nucleotide excision repair
C. Mismatch repair
D. Base excision repair
Answer: C
Rationales:
, • Correct (C): Microsatellite instability results from defects
in the mismatch repair (MMR) system, which normally
corrects replication errors in repetitive sequences.
• A: Homologous recombination repairs double-strand
breaks, not replication slippage causing MSI.
• B: Nucleotide excision repair removes bulky DNA adducts
(e.g., UV damage), not mismatch errors leading to MSI.
• D: Base excision repair corrects small base modifications
(e.g., oxidative damage), not microsatellite slippage.
Teaching Point: Mismatch repair defects cause microsatellite
instability in tumors.
3. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — Cellular Housekeeping
Stem: A neurodegenerative disease shows neuronal
accumulation of ubiquitinated proteins within cytoplasmic
inclusions. Which cellular process is most directly
impaired?
A. Lysosomal degradation via autophagy
B. Proteasomal degradation of misfolded proteins
C. Mitochondrial oxidative phosphorylation
D. Exocytosis of secretory proteins
Answer: B
Rationales:
, • Correct (B): Ubiquitination tags proteins for proteasomal
degradation; accumulation of ubiquitinated inclusions
indicates proteasome pathway impairment.
• A: Autophagy clears large aggregates and organelles but
ubiquitin-tagged short-lived proteins are primarily handled
by the proteasome.
• C: Mitochondrial dysfunction can contribute to disease but
does not directly explain ubiquitinated cytoplasmic
inclusions.
• D: Exocytosis is unrelated to intracellular clearance of
misfolded proteins.
Teaching Point: The ubiquitin–proteasome system clears many
misfolded proteins; its failure causes toxic accumulations.
4. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — Cellular Metabolism and
Mitochondrial Function
Stem: A patient presents with lactic acidosis and muscle
weakness. A muscle biopsy shows ragged-red fibers and
decreased activity of complex I (NADH dehydrogenase).
Which cellular organelle is defective, and how does this
produce lactic acidosis?
A. Lysosome; decreased macromolecule degradation
increases lactate
B. Endoplasmic reticulum; impaired protein synthesis
causes anaerobic metabolism
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 – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A newborn is found to have failure to thrive and
recurrent infections. Genetic testing reveals a nonsense
mutation in a gene encoding a protein required for V(D)J
recombination. Which mechanism most likely explains
how a nonsense mutation causes disease?
A. Gain of function via increased protein stability
B. Altered gene expression from promoter activation
C. Premature stop codon producing truncated,
nonfunctional protein
D. Increased mRNA stability leading to overproduction of
protein
Answer: C
Rationales:
, • Correct (C): Nonsense mutations introduce a premature
termination codon, producing truncated proteins that are
often nonfunctional or degraded by nonsense-mediated
decay, disrupting processes like V(D)J recombination.
• A: Gain-of-function with increased stability is more typical
of missense mutations that enhance activity, not classic
nonsense mutations.
• B: Promoter activation affects transcription initiation, not
the protein-coding sequence altered by a nonsense
mutation.
• D: Nonsense mutations typically decrease mRNA stability
via nonsense-mediated decay rather than increase it.
Teaching Point: Nonsense mutations often yield truncated
proteins or mRNA decay causing loss of function.
2. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — The Genome
Stem: A patient’s tumor shows microsatellite instability
(MSI). Which DNA repair pathway is most likely defective
in this tumor?
A. Homologous recombination repair
B. Nucleotide excision repair
C. Mismatch repair
D. Base excision repair
Answer: C
Rationales:
, • Correct (C): Microsatellite instability results from defects
in the mismatch repair (MMR) system, which normally
corrects replication errors in repetitive sequences.
• A: Homologous recombination repairs double-strand
breaks, not replication slippage causing MSI.
• B: Nucleotide excision repair removes bulky DNA adducts
(e.g., UV damage), not mismatch errors leading to MSI.
• D: Base excision repair corrects small base modifications
(e.g., oxidative damage), not microsatellite slippage.
Teaching Point: Mismatch repair defects cause microsatellite
instability in tumors.
3. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — Cellular Housekeeping
Stem: A neurodegenerative disease shows neuronal
accumulation of ubiquitinated proteins within cytoplasmic
inclusions. Which cellular process is most directly
impaired?
A. Lysosomal degradation via autophagy
B. Proteasomal degradation of misfolded proteins
C. Mitochondrial oxidative phosphorylation
D. Exocytosis of secretory proteins
Answer: B
Rationales:
, • Correct (B): Ubiquitination tags proteins for proteasomal
degradation; accumulation of ubiquitinated inclusions
indicates proteasome pathway impairment.
• A: Autophagy clears large aggregates and organelles but
ubiquitin-tagged short-lived proteins are primarily handled
by the proteasome.
• C: Mitochondrial dysfunction can contribute to disease but
does not directly explain ubiquitinated cytoplasmic
inclusions.
• D: Exocytosis is unrelated to intracellular clearance of
misfolded proteins.
Teaching Point: The ubiquitin–proteasome system clears many
misfolded proteins; its failure causes toxic accumulations.
4. Chapter Reference – Chapter 1: The Cell as a Unit of
Health and Disease — Cellular Metabolism and
Mitochondrial Function
Stem: A patient presents with lactic acidosis and muscle
weakness. A muscle biopsy shows ragged-red fibers and
decreased activity of complex I (NADH dehydrogenase).
Which cellular organelle is defective, and how does this
produce lactic acidosis?
A. Lysosome; decreased macromolecule degradation
increases lactate
B. Endoplasmic reticulum; impaired protein synthesis
causes anaerobic metabolism
