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 28-year-old woman undergoes genetic testing
after recurrent early miscarriages. The lab reports a
balanced reciprocal translocation between chromosomes
11 and 22. Which statement best explains why she is
phenotypically normal but has reproductive issues?
A. The translocation disrupts a single essential gene
causing dominant negative effects.
B. The translocation causes loss of large amounts of
genetic material in all cells.
C. Meiotic segregation produces gametes with unbalanced
chromosomal content.
D. Somatic mosaicism prevents expression of the
rearranged chromosomes.
Answer: C
,Rationale (correct): Balanced reciprocal translocations preserve
gene dosage in somatic cells, so carriers are often
phenotypically normal; however, during meiosis, segregation
can yield gametes with duplications and deletions, causing
miscarriages or offspring with abnormalities.
Rationale (A): If a single essential gene were disrupted with
dominant negative effect, the carrier would likely show a
phenotype, not be asymptomatic.
Rationale (B): Balanced translocations do not usually involve
net loss of genetic material in all somatic cells.
Rationale (D): Somatic mosaicism is unrelated to a balanced
germline translocation causing reproductive risk.
Teaching Point: Balanced translocations can be phenotypically
silent but produce unbalanced gametes.
2. Chapter Reference: The Genome
Stem: A patient’s tumor shows high mutation burden and
frameshift mutations in multiple tumor suppressor genes.
Which DNA repair pathway defect most likely contributed
to accumulation of frameshift mutations?
A. Nucleotide excision repair (NER)
B. Mismatch repair (MMR)
C. Base excision repair (BER)
D. Homologous recombination (HR)
Answer: B
,Rationale (correct): Mismatch repair corrects base–base
mismatches and insertion–deletion loops that cause frameshifts
during replication; MMR deficiency leads to microsatellite
instability and frequent frameshifts.
Rationale (A): NER removes bulky helix-distorting lesions (e.g.,
UV photoproducts), not replication-associated frameshifts.
Rationale (C): BER repairs small base modifications (e.g.,
oxidation), not insertion-deletion loops causing frameshifts.
Rationale (D): HR repairs double-strand breaks using a sister
chromatid template; defects cause chromosomal instability
rather than microsatellite frameshifts.
Teaching Point: MMR deficiency causes microsatellite instability
and frameshift mutations.
3. Chapter Reference: Cellular Housekeeping
Stem: A 60-year-old man with chronic alcoholism develops
macrocytic anemia; bone marrow exam shows
accumulation of large, dysfunctional mitochondria in
erythroid precursors. Dysfunction in which process best
explains accumulation of abnormal mitochondria?
A. Autophagy (mitophagy) impairment
B. Defective ubiquitin–proteasome protein degradation
C. Reduced lysosomal acid hydrolase production
D. Increased mitochondrial biogenesis due to oxidative
stress
Answer: A
, Rationale (correct): Mitophagy selectively removes damaged
mitochondria via autophagy; impairment leads to accumulation
of enlarged, dysfunctional mitochondria in cells.
Rationale (B): Ubiquitin–proteasome degrades individual
proteins, not whole organelles like mitochondria.
Rationale (C): Reduced lysosomal hydrolases impair general
autolysosomal degradation, but mitophagy is the more specific
mechanism for mitochondrial turnover.
Rationale (D): Increased biogenesis alone would increase
mitochondrial number but does not explain selective
accumulation of damaged mitochondria without impaired
removal.
Teaching Point: Mitophagy clears damaged mitochondria; its
failure causes mitochondrial accumulation.
4. Chapter Reference: Cellular Metabolism and
Mitochondrial Function
Stem: A newborn presents with severe lactic acidosis and
hypotonia. Biochemical testing shows deficient pyruvate
dehydrogenase complex (PDH) activity. Which cellular
consequence most directly results from PDH deficiency?
A. Increased flow of pyruvate into the TCA cycle
B. Accumulation of lactate due to enhanced conversion by
lactate dehydrogenase
C. Elevated oxidative phosphorylation with increased ATP
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 28-year-old woman undergoes genetic testing
after recurrent early miscarriages. The lab reports a
balanced reciprocal translocation between chromosomes
11 and 22. Which statement best explains why she is
phenotypically normal but has reproductive issues?
A. The translocation disrupts a single essential gene
causing dominant negative effects.
B. The translocation causes loss of large amounts of
genetic material in all cells.
C. Meiotic segregation produces gametes with unbalanced
chromosomal content.
D. Somatic mosaicism prevents expression of the
rearranged chromosomes.
Answer: C
,Rationale (correct): Balanced reciprocal translocations preserve
gene dosage in somatic cells, so carriers are often
phenotypically normal; however, during meiosis, segregation
can yield gametes with duplications and deletions, causing
miscarriages or offspring with abnormalities.
Rationale (A): If a single essential gene were disrupted with
dominant negative effect, the carrier would likely show a
phenotype, not be asymptomatic.
Rationale (B): Balanced translocations do not usually involve
net loss of genetic material in all somatic cells.
Rationale (D): Somatic mosaicism is unrelated to a balanced
germline translocation causing reproductive risk.
Teaching Point: Balanced translocations can be phenotypically
silent but produce unbalanced gametes.
2. Chapter Reference: The Genome
Stem: A patient’s tumor shows high mutation burden and
frameshift mutations in multiple tumor suppressor genes.
Which DNA repair pathway defect most likely contributed
to accumulation of frameshift mutations?
A. Nucleotide excision repair (NER)
B. Mismatch repair (MMR)
C. Base excision repair (BER)
D. Homologous recombination (HR)
Answer: B
,Rationale (correct): Mismatch repair corrects base–base
mismatches and insertion–deletion loops that cause frameshifts
during replication; MMR deficiency leads to microsatellite
instability and frequent frameshifts.
Rationale (A): NER removes bulky helix-distorting lesions (e.g.,
UV photoproducts), not replication-associated frameshifts.
Rationale (C): BER repairs small base modifications (e.g.,
oxidation), not insertion-deletion loops causing frameshifts.
Rationale (D): HR repairs double-strand breaks using a sister
chromatid template; defects cause chromosomal instability
rather than microsatellite frameshifts.
Teaching Point: MMR deficiency causes microsatellite instability
and frameshift mutations.
3. Chapter Reference: Cellular Housekeeping
Stem: A 60-year-old man with chronic alcoholism develops
macrocytic anemia; bone marrow exam shows
accumulation of large, dysfunctional mitochondria in
erythroid precursors. Dysfunction in which process best
explains accumulation of abnormal mitochondria?
A. Autophagy (mitophagy) impairment
B. Defective ubiquitin–proteasome protein degradation
C. Reduced lysosomal acid hydrolase production
D. Increased mitochondrial biogenesis due to oxidative
stress
Answer: A
, Rationale (correct): Mitophagy selectively removes damaged
mitochondria via autophagy; impairment leads to accumulation
of enlarged, dysfunctional mitochondria in cells.
Rationale (B): Ubiquitin–proteasome degrades individual
proteins, not whole organelles like mitochondria.
Rationale (C): Reduced lysosomal hydrolases impair general
autolysosomal degradation, but mitophagy is the more specific
mechanism for mitochondrial turnover.
Rationale (D): Increased biogenesis alone would increase
mitochondrial number but does not explain selective
accumulation of damaged mitochondria without impaired
removal.
Teaching Point: Mitophagy clears damaged mitochondria; its
failure causes mitochondrial accumulation.
4. Chapter Reference: Cellular Metabolism and
Mitochondrial Function
Stem: A newborn presents with severe lactic acidosis and
hypotonia. Biochemical testing shows deficient pyruvate
dehydrogenase complex (PDH) activity. Which cellular
consequence most directly results from PDH deficiency?
A. Increased flow of pyruvate into the TCA cycle
B. Accumulation of lactate due to enhanced conversion by
lactate dehydrogenase
C. Elevated oxidative phosphorylation with increased ATP
