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
Stem: A 28-year-old man has recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation early in a
gene encoding a Toll-like receptor, producing a truncated
nonfunctional protein. Which mechanism best explains how the
frameshift mutation causes dysfunctional receptor protein?
A. Altered transcription factor binding to the promoter
B. Shifted reading frame producing premature stop codon and
truncated protein
C. Single amino acid substitution causing gain of function
D. Epigenetic methylation silencing gene expression
Answer: B
Rationale — Correct (B): Frameshift mutations shift the codon
reading frame, often generating premature stop codons and
,truncated, nonfunctional proteins. This explains loss of Toll-like
receptor activity and recurrent infections.
Rationale — Incorrect (A): Promoter binding changes affect
transcription levels, not reading-frame-derived truncation.
Rationale — Incorrect (C): A single amino acid substitution is a
missense mutation; this is not the same as a frameshift
producing truncation.
Rationale — Incorrect (D): DNA methylation silences expression
but does not produce truncated proteins from altered coding
sequence.
Teaching Point: Frameshift mutations often produce premature
stop codons and truncated, nonfunctional proteins.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A newborn screen identifies elevated phenylalanine.
Molecular testing shows a mutation that reduces
tetrahydrobiopterin (BH4) cofactor recycling but leaves PAH
enzyme levels normal. Which process is primarily disrupted?
A. Protein folding in the ER
B. Cofactor-dependent enzyme activity in metabolic pathways
C. Transcription of the PAH gene
D. Mitochondrial oxidative phosphorylation
Answer: B
,Rationale — Correct (B): BH4 is an essential cofactor for
phenylalanine hydroxylase (PAH); impaired BH4 recycling
decreases enzyme activity despite normal PAH protein levels,
causing hyperphenylalaninemia.
Rationale — Incorrect (A): ER protein folding defects would
alter protein levels or cause misfolding, not cofactor recycling.
Rationale — Incorrect (C): Normal PAH levels indicate
transcription is intact.
Rationale — Incorrect (D): Oxidative phosphorylation is
unrelated to BH4-dependent hydroxylation.
Teaching Point: Cofactors are essential for enzyme activity even
when protein levels are normal.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A liver biopsy shows numerous Mallory bodies
(intracellular aggregates) in hepatocytes of a patient with
chronic alcohol use. Which intracellular disposal system is most
directly responsible for clearing damaged cytoskeletal proteins
and is overwhelmed here?
A. Ubiquitin–proteasome pathway
B. Phagocytosis by Kupffer cells
C. Lysosomal autophagy
D. Mitochondrial mitophagy
Answer: A
, Rationale — Correct (A): The ubiquitin–proteasome system
targets soluble, damaged cytoskeletal and regulatory proteins
for degradation; when overwhelmed, aggregates such as
Mallory bodies form.
Rationale — Incorrect (B): Kupffer cells phagocytose
extracellular debris, not intracellular protein aggregates.
Rationale — Incorrect (C): Autophagy handles larger organelles
and aggregates but Mallory bodies reflect failure primarily of
ubiquitin–proteasome clearance.
Rationale — Incorrect (D): Mitophagy specifically targets
mitochondria, not cytoskeletal proteins.
Teaching Point: Ubiquitin–proteasome failure leads to
intracellular protein aggregate accumulation.
4
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A patient with an inherited defect in lysosomal enzyme
trafficking accumulates undegraded glycolipids in neurons.
Which cellular process is primarily defective?
A. Proteasomal degradation of ubiquitinated proteins
B. Receptor-mediated endocytosis
C. Mannose-6-phosphate tagging and transport to lysosomes
D. Autocrine growth factor signaling
Answer: C
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
Stem: A 28-year-old man has recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation early in a
gene encoding a Toll-like receptor, producing a truncated
nonfunctional protein. Which mechanism best explains how the
frameshift mutation causes dysfunctional receptor protein?
A. Altered transcription factor binding to the promoter
B. Shifted reading frame producing premature stop codon and
truncated protein
C. Single amino acid substitution causing gain of function
D. Epigenetic methylation silencing gene expression
Answer: B
Rationale — Correct (B): Frameshift mutations shift the codon
reading frame, often generating premature stop codons and
,truncated, nonfunctional proteins. This explains loss of Toll-like
receptor activity and recurrent infections.
Rationale — Incorrect (A): Promoter binding changes affect
transcription levels, not reading-frame-derived truncation.
Rationale — Incorrect (C): A single amino acid substitution is a
missense mutation; this is not the same as a frameshift
producing truncation.
Rationale — Incorrect (D): DNA methylation silences expression
but does not produce truncated proteins from altered coding
sequence.
Teaching Point: Frameshift mutations often produce premature
stop codons and truncated, nonfunctional proteins.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A newborn screen identifies elevated phenylalanine.
Molecular testing shows a mutation that reduces
tetrahydrobiopterin (BH4) cofactor recycling but leaves PAH
enzyme levels normal. Which process is primarily disrupted?
A. Protein folding in the ER
B. Cofactor-dependent enzyme activity in metabolic pathways
C. Transcription of the PAH gene
D. Mitochondrial oxidative phosphorylation
Answer: B
,Rationale — Correct (B): BH4 is an essential cofactor for
phenylalanine hydroxylase (PAH); impaired BH4 recycling
decreases enzyme activity despite normal PAH protein levels,
causing hyperphenylalaninemia.
Rationale — Incorrect (A): ER protein folding defects would
alter protein levels or cause misfolding, not cofactor recycling.
Rationale — Incorrect (C): Normal PAH levels indicate
transcription is intact.
Rationale — Incorrect (D): Oxidative phosphorylation is
unrelated to BH4-dependent hydroxylation.
Teaching Point: Cofactors are essential for enzyme activity even
when protein levels are normal.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A liver biopsy shows numerous Mallory bodies
(intracellular aggregates) in hepatocytes of a patient with
chronic alcohol use. Which intracellular disposal system is most
directly responsible for clearing damaged cytoskeletal proteins
and is overwhelmed here?
A. Ubiquitin–proteasome pathway
B. Phagocytosis by Kupffer cells
C. Lysosomal autophagy
D. Mitochondrial mitophagy
Answer: A
, Rationale — Correct (A): The ubiquitin–proteasome system
targets soluble, damaged cytoskeletal and regulatory proteins
for degradation; when overwhelmed, aggregates such as
Mallory bodies form.
Rationale — Incorrect (B): Kupffer cells phagocytose
extracellular debris, not intracellular protein aggregates.
Rationale — Incorrect (C): Autophagy handles larger organelles
and aggregates but Mallory bodies reflect failure primarily of
ubiquitin–proteasome clearance.
Rationale — Incorrect (D): Mitophagy specifically targets
mitochondria, not cytoskeletal proteins.
Teaching Point: Ubiquitin–proteasome failure leads to
intracellular protein aggregate accumulation.
4
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A patient with an inherited defect in lysosomal enzyme
trafficking accumulates undegraded glycolipids in neurons.
Which cellular process is primarily defective?
A. Proteasomal degradation of ubiquitinated proteins
B. Receptor-mediated endocytosis
C. Mannose-6-phosphate tagging and transport to lysosomes
D. Autocrine growth factor signaling
Answer: C
