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
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A 6-year-old boy presents with progressive neurologic
deterioration. Genetic testing shows a defect in a lysosomal
hydrolase causing accumulation of undegraded substrates within
lysosomes. Which cellular process is primarily disrupted?
A. Ubiquitin–proteasome degradation of cytosolic proteins
B. Autophagy–lysosomal pathway for organelle and
macromolecule turnover
C. Mitochondrial oxidative phosphorylation
D. Endoplasmic reticulum–associated degradation (ERAD)
Answer: B
,Rationale (correct): The lysosomal hydrolase defect leads to
failure of the autophagy–lysosomal system, causing
accumulation of substrates and enlarged lysosomes; this
underlies many storage disorders. Autophagy delivers
cytoplasmic content to lysosomes for degradation.
Rationale (A): Ubiquitin–proteasome handles short-lived and
misfolded cytosolic/nuclear proteins, not large macromolecular
or organelle substrates stored in lysosomes.
Rationale (C): Mitochondrial oxidative phosphorylation defects
impair ATP production; they do not directly cause lysosomal
substrate accumulation.
Rationale (D): ERAD removes misfolded proteins from the ER
for proteasomal degradation; it is distinct from lysosomal
hydrolase function.
Teaching Point: Lysosomal hydrolase defects disrupt
autophagy–lysosomal turnover causing storage disease
pathology.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A tumor shows loss-of-function mutation in a DNA
mismatch repair gene (MSH2). Which genomic consequence is
,most expected in tumor cells?
A. Chromosomal translocations with balanced breakpoints
B. Microsatellite instability due to replication errors in short
repeats
C. Increased double-strand breaks due to defective
nonhomologous end joining
D. Hypomethylation of promoter CpG islands
Answer: B
Rationale (correct): Loss of mismatch repair proteins like
MSH2 leads to failure to correct replication slippage at
microsatellite repeats, producing microsatellite instability. This
is characteristic of certain carcinomas.
Rationale (A): Chromosomal translocations typically arise from
double-strand break misrepair, not primarily mismatch repair
defects.
Rationale (C): Nonhomologous end joining defects cause
problems with double-strand break repair, not mismatch
correction of single-base or insertion-deletion errors.
Rationale (D): Promoter methylation changes are epigenetic;
while tumors may have methylation alterations, mismatch repair
loss does not directly cause promoter hypomethylation.
Teaching Point: Mismatch repair defects cause microsatellite
instability from uncorrected replication errors.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
, The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A patient with ischemic myocardial injury develops
reperfusion. Which mitochondrial event during reperfusion most
directly contributes to cell death?
A. Restoration of ATP synthesis preventing apoptosis
B. Massive generation of reactive oxygen species (ROS)
triggering mitochondrial permeability transition
C. Activation of mitochondrial biogenesis improving cellular
recovery
D. Increased mitochondrial fusion promoting cell survival
Answer: B
Rationale (correct): Reperfusion commonly causes a burst of
ROS that triggers opening of the mitochondrial permeability
transition pore, loss of membrane potential, and necrotic and
apoptotic cell death.
Rationale (A): While ATP restoration can help, the early
reperfusion burst of ROS often overwhelms protective processes
and promotes death rather than immediate recovery.
Rationale (C): Mitochondrial biogenesis is a slower adaptive
response and does not account for the acute injury of
reperfusion.
Rationale (D): Mitochondrial fusion can be protective, but
acute reperfusion injury is characterized primarily by ROS and
permeability transition.
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A 6-year-old boy presents with progressive neurologic
deterioration. Genetic testing shows a defect in a lysosomal
hydrolase causing accumulation of undegraded substrates within
lysosomes. Which cellular process is primarily disrupted?
A. Ubiquitin–proteasome degradation of cytosolic proteins
B. Autophagy–lysosomal pathway for organelle and
macromolecule turnover
C. Mitochondrial oxidative phosphorylation
D. Endoplasmic reticulum–associated degradation (ERAD)
Answer: B
,Rationale (correct): The lysosomal hydrolase defect leads to
failure of the autophagy–lysosomal system, causing
accumulation of substrates and enlarged lysosomes; this
underlies many storage disorders. Autophagy delivers
cytoplasmic content to lysosomes for degradation.
Rationale (A): Ubiquitin–proteasome handles short-lived and
misfolded cytosolic/nuclear proteins, not large macromolecular
or organelle substrates stored in lysosomes.
Rationale (C): Mitochondrial oxidative phosphorylation defects
impair ATP production; they do not directly cause lysosomal
substrate accumulation.
Rationale (D): ERAD removes misfolded proteins from the ER
for proteasomal degradation; it is distinct from lysosomal
hydrolase function.
Teaching Point: Lysosomal hydrolase defects disrupt
autophagy–lysosomal turnover causing storage disease
pathology.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A tumor shows loss-of-function mutation in a DNA
mismatch repair gene (MSH2). Which genomic consequence is
,most expected in tumor cells?
A. Chromosomal translocations with balanced breakpoints
B. Microsatellite instability due to replication errors in short
repeats
C. Increased double-strand breaks due to defective
nonhomologous end joining
D. Hypomethylation of promoter CpG islands
Answer: B
Rationale (correct): Loss of mismatch repair proteins like
MSH2 leads to failure to correct replication slippage at
microsatellite repeats, producing microsatellite instability. This
is characteristic of certain carcinomas.
Rationale (A): Chromosomal translocations typically arise from
double-strand break misrepair, not primarily mismatch repair
defects.
Rationale (C): Nonhomologous end joining defects cause
problems with double-strand break repair, not mismatch
correction of single-base or insertion-deletion errors.
Rationale (D): Promoter methylation changes are epigenetic;
while tumors may have methylation alterations, mismatch repair
loss does not directly cause promoter hypomethylation.
Teaching Point: Mismatch repair defects cause microsatellite
instability from uncorrected replication errors.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease
, The Genome · Cellular Housekeeping · Cellular Metabolism and
Mitochondrial Function · Cellular Activation · Growth Factors
and Receptors · Extracellular Matrix · Maintaining Cell
Populations
Stem: A patient with ischemic myocardial injury develops
reperfusion. Which mitochondrial event during reperfusion most
directly contributes to cell death?
A. Restoration of ATP synthesis preventing apoptosis
B. Massive generation of reactive oxygen species (ROS)
triggering mitochondrial permeability transition
C. Activation of mitochondrial biogenesis improving cellular
recovery
D. Increased mitochondrial fusion promoting cell survival
Answer: B
Rationale (correct): Reperfusion commonly causes a burst of
ROS that triggers opening of the mitochondrial permeability
transition pore, loss of membrane potential, and necrotic and
apoptotic cell death.
Rationale (A): While ATP restoration can help, the early
reperfusion burst of ROS often overwhelms protective processes
and promotes death rather than immediate recovery.
Rationale (C): Mitochondrial biogenesis is a slower adaptive
response and does not account for the acute injury of
reperfusion.
Rationale (D): Mitochondrial fusion can be protective, but
acute reperfusion injury is characterized primarily by ROS and
permeability transition.
