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 1 — The Genome
A 6-year-old boy presents with recurrent infections and failure
to thrive. Genetic testing shows an inability to repair DNA
double-strand breaks caused by ionizing radiation. Which
cellular process is most likely defective?
A. Nucleotide excision repair
B. Base excision repair
C. Nonhomologous end joining (NHEJ)
D. Mismatch repair
Correct Answer: C
Rationale — Correct: NHEJ is a principal pathway to repair DNA
double-strand breaks in somatic cells; defects produce
radiosensitivity and immunodeficiency, consistent with the
clinical picture. Robbins describes NHEJ as critical for repairing
,double-strand breaks and for V(D)J recombination.
A (wrong): Nucleotide excision repair corrects bulky helix-
distorting lesions (e.g., UV-induced thymine dimers), not
double-strand breaks.
B (wrong): Base excision repair fixes small non-helix-distorting
base lesions (oxidation, alkylation), not double-strand breaks.
D (wrong): Mismatch repair corrects replication errors
(mismatches/loops), not ionizing-radiation–induced double-
strand breaks.
Teaching Point: NHEJ repairs double-strand DNA breaks and its
failure causes radiosensitivity and immunodeficiency.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(DNA repair pathways)
2. Chapter 1 — Cellular Housekeeping
A patient’s biopsy reveals cytoplasmic accumulation of
ubiquitinated proteins forming inclusion bodies. Which
organelle–pathway defect most directly explains this finding?
A. Lysosomal hydrolase deficiency
B. Impaired proteasome (ubiquitin–proteasome) system
C. Defective rough endoplasmic reticulum protein folding (UPR)
only
D. Mitochondrial oxidative phosphorylation defect
Correct Answer: B
,Rationale — Correct: The ubiquitin–proteasome system
degrades short-lived and misfolded proteins; impairment leads
to accumulation of ubiquitinated proteins and inclusion bodies.
Robbins details the proteasome’s role in protein quality control.
A (wrong): Lysosomal enzyme defects cause storage of
macromolecules in lysosomes, typically PAS/Gomori-positive,
not ubiquitinated cytosolic inclusions.
C (wrong): Unfolded protein response (ER stress) may increase
misfolded proteins but the direct accumulation of ubiquitinated
proteins indicates proteasomal failure rather than UPR alone.
D (wrong): Mitochondrial OXPHOS defects cause energy failure,
lactic acidosis, not primary ubiquitinated protein inclusions.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded proteins; its failure causes ubiquitinated inclusions.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
housekeeping (protein degradation systems)
3. Chapter 1 — Cellular Metabolism and Mitochondrial
Function
An adult presents with exercise intolerance and intermittent
lactic acidosis. Muscle biopsy shows ragged-red fibers and
abnormal mitochondria. Which metabolic defect best explains
the lactic acidosis?
A. Deficient glycolytic enzymes in cytosol
B. Impaired mitochondrial oxidative phosphorylation
, C. Excessive hepatic gluconeogenesis
D. Failure of pentose phosphate pathway
Correct Answer: B
Rationale — Correct: Impaired oxidative phosphorylation
forces cells to rely on anaerobic glycolysis, increasing lactate
production; ragged-red fibers reflect dysfunctional
mitochondria. Robbins explains mitochondrial defects cause
lactic acidosis and myopathy.
A (wrong): Glycolytic enzyme defects typically produce exercise
intolerance but do not classically cause ragged-red fibers or
chronic mitochondrial structural changes.
C (wrong): Increased hepatic gluconeogenesis would not
directly produce peripheral lactic acidosis or mitochondrial
structural abnormalities.
D (wrong): Pentose phosphate pathway defects impair NADPH
generation but are not primary causes of lactic acidosis with
ragged-red fibers.
Teaching Point: Mitochondrial OXPHOS defects elevate lactate
due to compensatory anaerobic glycolysis.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
metabolism and mitochondrial function
4. Chapter 1 — Cellular Activation
A patient with sepsis has neutrophils that fail to generate
reactive oxygen species (ROS) despite normal neutrophil counts
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter 1 — The Genome
A 6-year-old boy presents with recurrent infections and failure
to thrive. Genetic testing shows an inability to repair DNA
double-strand breaks caused by ionizing radiation. Which
cellular process is most likely defective?
A. Nucleotide excision repair
B. Base excision repair
C. Nonhomologous end joining (NHEJ)
D. Mismatch repair
Correct Answer: C
Rationale — Correct: NHEJ is a principal pathway to repair DNA
double-strand breaks in somatic cells; defects produce
radiosensitivity and immunodeficiency, consistent with the
clinical picture. Robbins describes NHEJ as critical for repairing
,double-strand breaks and for V(D)J recombination.
A (wrong): Nucleotide excision repair corrects bulky helix-
distorting lesions (e.g., UV-induced thymine dimers), not
double-strand breaks.
B (wrong): Base excision repair fixes small non-helix-distorting
base lesions (oxidation, alkylation), not double-strand breaks.
D (wrong): Mismatch repair corrects replication errors
(mismatches/loops), not ionizing-radiation–induced double-
strand breaks.
Teaching Point: NHEJ repairs double-strand DNA breaks and its
failure causes radiosensitivity and immunodeficiency.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — The Genome
(DNA repair pathways)
2. Chapter 1 — Cellular Housekeeping
A patient’s biopsy reveals cytoplasmic accumulation of
ubiquitinated proteins forming inclusion bodies. Which
organelle–pathway defect most directly explains this finding?
A. Lysosomal hydrolase deficiency
B. Impaired proteasome (ubiquitin–proteasome) system
C. Defective rough endoplasmic reticulum protein folding (UPR)
only
D. Mitochondrial oxidative phosphorylation defect
Correct Answer: B
,Rationale — Correct: The ubiquitin–proteasome system
degrades short-lived and misfolded proteins; impairment leads
to accumulation of ubiquitinated proteins and inclusion bodies.
Robbins details the proteasome’s role in protein quality control.
A (wrong): Lysosomal enzyme defects cause storage of
macromolecules in lysosomes, typically PAS/Gomori-positive,
not ubiquitinated cytosolic inclusions.
C (wrong): Unfolded protein response (ER stress) may increase
misfolded proteins but the direct accumulation of ubiquitinated
proteins indicates proteasomal failure rather than UPR alone.
D (wrong): Mitochondrial OXPHOS defects cause energy failure,
lactic acidosis, not primary ubiquitinated protein inclusions.
Teaching Point: The ubiquitin–proteasome pathway clears
misfolded proteins; its failure causes ubiquitinated inclusions.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
housekeeping (protein degradation systems)
3. Chapter 1 — Cellular Metabolism and Mitochondrial
Function
An adult presents with exercise intolerance and intermittent
lactic acidosis. Muscle biopsy shows ragged-red fibers and
abnormal mitochondria. Which metabolic defect best explains
the lactic acidosis?
A. Deficient glycolytic enzymes in cytosol
B. Impaired mitochondrial oxidative phosphorylation
, C. Excessive hepatic gluconeogenesis
D. Failure of pentose phosphate pathway
Correct Answer: B
Rationale — Correct: Impaired oxidative phosphorylation
forces cells to rely on anaerobic glycolysis, increasing lactate
production; ragged-red fibers reflect dysfunctional
mitochondria. Robbins explains mitochondrial defects cause
lactic acidosis and myopathy.
A (wrong): Glycolytic enzyme defects typically produce exercise
intolerance but do not classically cause ragged-red fibers or
chronic mitochondrial structural changes.
C (wrong): Increased hepatic gluconeogenesis would not
directly produce peripheral lactic acidosis or mitochondrial
structural abnormalities.
D (wrong): Pentose phosphate pathway defects impair NADPH
generation but are not primary causes of lactic acidosis with
ragged-red fibers.
Teaching Point: Mitochondrial OXPHOS defects elevate lactate
due to compensatory anaerobic glycolysis.
Citation: Robbins & Cotran, 10th Ed., Chapter 1 — Cellular
metabolism and mitochondrial function
4. Chapter 1 — Cellular Activation
A patient with sepsis has neutrophils that fail to generate
reactive oxygen species (ROS) despite normal neutrophil counts
