NR 507 / NR507 Advanced Pathophysiology
Midterm Exam ACTUAL EXAM | Questions &
Verified Answers Latest Update –
Chamberlain University
1. A 22-year-old man presents with muscle cramps after exercise. Serum CK is 1
800 U/L, lactate 6 mmol/L, and forearm ischemic testing shows no rise in
ammonia. Which pathophysiologic mechanism is MOST likely responsible?
A. Defective dystrophin glycoprotein complex
B. Myophosphorylase deficiency
C. Acid maltase deficiency
D. Mitochondrial tRNA mutation
Correct Answer: B
Rationale: Absent ammonia rise during ischemic exercise is pathognomonic for
myophosphorylase deficiency (McArdle disease), preventing glycogenolysis and ATP
generation → cramps and elevated lactate. Dystrophinopathy (A) causes CK rise but
normal ammonia. Acid maltase (C) is a lysosomal defect with progressive weakness,
not exercise intolerance. Mitochondrial mutations (D) elevate lactate but do not impair
ammonia production from adenylate kinase.
2. Mutations in the LMNA gene encoding lamin A/C lead to premature cell
senescence via which cellular process?
A. Impaired formation of the desmosome
B. Defective DNA-damage response and nuclear fragility
C. Disrupted microtubule assembly
D. Accumulation of misfolded actin filaments
Correct Answer: B
,Rationale: Lamin A/C maintains nuclear envelope integrity; mutations cause nuclear
blebbing, chromatin leakage, and persistent DNA-damage signaling → senescence.
Desmosomes (A) are membrane junctions unrelated to lamin. Microtubules (C) are
polymerized by tubulins, not lamins. Actin (D) is cytoskeletal and unaffected by LMNA.
3. A 4-week-old infant exhibits hypotonia, cardiomegaly, and profound muscle
weakness. Muscle biopsy shows periodic-acid-Schiff–positive vacuoles. Which
enzymatic defect is present?
A. Lysosomal acid α-1,4-glucosidase
B. Muscle glycogen phosphorylase
C. Debranching enzyme
D. Branching enzyme
Correct Answer: A
Rationale: Infantile Pompe disease (acid maltase deficiency) is a lysosomal storage
disorder with glycogen accumulation in vacuoles staining PAS-positive.
Myophosphorylase (B) presents later with exercise intolerance. Debrancher (C) and
brancher (D) deficiencies produce hepatic or neuromuscular symptoms but not infantile
cardiomyopathy.
4. Chronic myelogenous leukemia is characterized by the BCR-ABL fusion. Which
pathophysiologic outcome is MOST critical for leukemogenesis?
A. Constitutive receptor tyrosine-kinase activity
B. Loss of G1/S checkpoint control
C. Defective DNA mismatch repair
D. Aberrant histone acetylation
Correct Answer: A
Rationale: BCR-ABL forms a constitutively active tyrosine kinase driving proliferation
and inhibiting apoptosis. G1/S loss (B) is downstream but not the primary event.
Mismatch repair (C) is seen in Lynch syndrome. Histone acetylation (D) is epigenetic,
not the defining lesion in CML.
, 5. A 35-year-old woman with systemic lupus erythematosus develops nephritis.
Renal biopsy reveals mesangial and endothelial cell proliferation with
subendothelial immune deposits. Which complement pathway is PRIMARILY
activated?
A. Classical
B. Lectin
C. Alternative
D. Terminal only
Correct Answer: A
Rationale: Immune-complex deposition in lupus engages C1q → classical pathway
activation, producing C4d and C3b deposition. Lectin (B) is initiated by mannose-binding
lectin, not immune complexes. Alternative (C) may amplify but is not primary. Terminal
(D) requires upstream activation.
6. A 60-year-old man with chronic bronchitis expectorates thick, green sputum.
Which inflammatory cell type and mediator pair is MOST responsible for sputum
color?
A. Macrophage + prostaglandin E2
B. Eosinophil + leukotriene C4
C. Neutrophil + myeloperoxidase
D. Mast cell + histamine
Correct Answer: C
Rationale: Green color derives from myeloperoxidase released by neutrophils recruited
during bacterial infection. Macrophages (A) produce clear or yellowish fluid. Eosinophils
(B) yield white clumps in asthma. Mast-cell histamine (D) is not pigmented.
7. Which epigenetic modification MOST directly leads to transcriptional silencing of
a tumor-suppressor gene?
A. Histone H3 lysine 4 trimethylation
B. Histone H3 lysine 27 trimethylation
C. Histone H3 lysine 9 acetylation
D. DNA cytosine hydroxymethylation
, Correct Answer: B
Rationale: H3K27me3 is catalyzed by PRC2 (EZH2) and recruits chromatin-compacting
proteins → gene silencing. H3K4me3 (A) marks active promoters. H3K9ac (C) opens
chromatin. 5-hmC (D) is an intermediate in demethylation and is permissive.
8. A 19-year-old African man presents with painful crises and hemoglobin 8 g/dL.
Which vaso-occlusive trigger is MOST related to the dehydration-induced
increase in HbS polymerization?
A. Increased 2,3-BPG shifting the oxygen dissociation curve rightward
B. Reduced MCHC lowering intracellular HbS concentration
C. Increased pH raising oxygen affinity
D. Increased plasma osmolality drawing water from erythrocytes
Correct Answer: D
Rationale: Dehydration raises plasma osmolality → water efflux from RBCs → higher
mean corpuscular HbS concentration and accelerated polymer formation. 2,3-BPG (A)
shifts curve right but is not primary trigger. Lower MCHC (B) would inhibit, not promote,
polymer. Alkalosis (C) increases affinity, reducing deoxy-HbS and polymer.
9. A 50-year-old man develops ascending areflexic weakness 10 days after a viral
illness. CSF shows albuminocytologic dissociation. Which pathophysiologic
mechanism underlies his weakness?
A. Demyelination of peripheral nerves by molecular mimicry
B. IgG-mediated destruction of neuromuscular junction
C. Anterior horn cell apoptosis
D. Microvascular occlusion of vasa nervorum
Correct Answer: A
Rationale: Guillain-Barré syndrome is post-infectious molecular mimicry with antibodies
to gangliosides → segmental demyelination. NMJ (B) is affected in myasthenia.
Anterior horn (C) is poliomyelitis. Microvascular occlusion (D) occurs in vasculitic
neuropathy, not GBS.
Midterm Exam ACTUAL EXAM | Questions &
Verified Answers Latest Update –
Chamberlain University
1. A 22-year-old man presents with muscle cramps after exercise. Serum CK is 1
800 U/L, lactate 6 mmol/L, and forearm ischemic testing shows no rise in
ammonia. Which pathophysiologic mechanism is MOST likely responsible?
A. Defective dystrophin glycoprotein complex
B. Myophosphorylase deficiency
C. Acid maltase deficiency
D. Mitochondrial tRNA mutation
Correct Answer: B
Rationale: Absent ammonia rise during ischemic exercise is pathognomonic for
myophosphorylase deficiency (McArdle disease), preventing glycogenolysis and ATP
generation → cramps and elevated lactate. Dystrophinopathy (A) causes CK rise but
normal ammonia. Acid maltase (C) is a lysosomal defect with progressive weakness,
not exercise intolerance. Mitochondrial mutations (D) elevate lactate but do not impair
ammonia production from adenylate kinase.
2. Mutations in the LMNA gene encoding lamin A/C lead to premature cell
senescence via which cellular process?
A. Impaired formation of the desmosome
B. Defective DNA-damage response and nuclear fragility
C. Disrupted microtubule assembly
D. Accumulation of misfolded actin filaments
Correct Answer: B
,Rationale: Lamin A/C maintains nuclear envelope integrity; mutations cause nuclear
blebbing, chromatin leakage, and persistent DNA-damage signaling → senescence.
Desmosomes (A) are membrane junctions unrelated to lamin. Microtubules (C) are
polymerized by tubulins, not lamins. Actin (D) is cytoskeletal and unaffected by LMNA.
3. A 4-week-old infant exhibits hypotonia, cardiomegaly, and profound muscle
weakness. Muscle biopsy shows periodic-acid-Schiff–positive vacuoles. Which
enzymatic defect is present?
A. Lysosomal acid α-1,4-glucosidase
B. Muscle glycogen phosphorylase
C. Debranching enzyme
D. Branching enzyme
Correct Answer: A
Rationale: Infantile Pompe disease (acid maltase deficiency) is a lysosomal storage
disorder with glycogen accumulation in vacuoles staining PAS-positive.
Myophosphorylase (B) presents later with exercise intolerance. Debrancher (C) and
brancher (D) deficiencies produce hepatic or neuromuscular symptoms but not infantile
cardiomyopathy.
4. Chronic myelogenous leukemia is characterized by the BCR-ABL fusion. Which
pathophysiologic outcome is MOST critical for leukemogenesis?
A. Constitutive receptor tyrosine-kinase activity
B. Loss of G1/S checkpoint control
C. Defective DNA mismatch repair
D. Aberrant histone acetylation
Correct Answer: A
Rationale: BCR-ABL forms a constitutively active tyrosine kinase driving proliferation
and inhibiting apoptosis. G1/S loss (B) is downstream but not the primary event.
Mismatch repair (C) is seen in Lynch syndrome. Histone acetylation (D) is epigenetic,
not the defining lesion in CML.
, 5. A 35-year-old woman with systemic lupus erythematosus develops nephritis.
Renal biopsy reveals mesangial and endothelial cell proliferation with
subendothelial immune deposits. Which complement pathway is PRIMARILY
activated?
A. Classical
B. Lectin
C. Alternative
D. Terminal only
Correct Answer: A
Rationale: Immune-complex deposition in lupus engages C1q → classical pathway
activation, producing C4d and C3b deposition. Lectin (B) is initiated by mannose-binding
lectin, not immune complexes. Alternative (C) may amplify but is not primary. Terminal
(D) requires upstream activation.
6. A 60-year-old man with chronic bronchitis expectorates thick, green sputum.
Which inflammatory cell type and mediator pair is MOST responsible for sputum
color?
A. Macrophage + prostaglandin E2
B. Eosinophil + leukotriene C4
C. Neutrophil + myeloperoxidase
D. Mast cell + histamine
Correct Answer: C
Rationale: Green color derives from myeloperoxidase released by neutrophils recruited
during bacterial infection. Macrophages (A) produce clear or yellowish fluid. Eosinophils
(B) yield white clumps in asthma. Mast-cell histamine (D) is not pigmented.
7. Which epigenetic modification MOST directly leads to transcriptional silencing of
a tumor-suppressor gene?
A. Histone H3 lysine 4 trimethylation
B. Histone H3 lysine 27 trimethylation
C. Histone H3 lysine 9 acetylation
D. DNA cytosine hydroxymethylation
, Correct Answer: B
Rationale: H3K27me3 is catalyzed by PRC2 (EZH2) and recruits chromatin-compacting
proteins → gene silencing. H3K4me3 (A) marks active promoters. H3K9ac (C) opens
chromatin. 5-hmC (D) is an intermediate in demethylation and is permissive.
8. A 19-year-old African man presents with painful crises and hemoglobin 8 g/dL.
Which vaso-occlusive trigger is MOST related to the dehydration-induced
increase in HbS polymerization?
A. Increased 2,3-BPG shifting the oxygen dissociation curve rightward
B. Reduced MCHC lowering intracellular HbS concentration
C. Increased pH raising oxygen affinity
D. Increased plasma osmolality drawing water from erythrocytes
Correct Answer: D
Rationale: Dehydration raises plasma osmolality → water efflux from RBCs → higher
mean corpuscular HbS concentration and accelerated polymer formation. 2,3-BPG (A)
shifts curve right but is not primary trigger. Lower MCHC (B) would inhibit, not promote,
polymer. Alkalosis (C) increases affinity, reducing deoxy-HbS and polymer.
9. A 50-year-old man develops ascending areflexic weakness 10 days after a viral
illness. CSF shows albuminocytologic dissociation. Which pathophysiologic
mechanism underlies his weakness?
A. Demyelination of peripheral nerves by molecular mimicry
B. IgG-mediated destruction of neuromuscular junction
C. Anterior horn cell apoptosis
D. Microvascular occlusion of vasa nervorum
Correct Answer: A
Rationale: Guillain-Barré syndrome is post-infectious molecular mimicry with antibodies
to gangliosides → segmental demyelination. NMJ (B) is affected in myasthenia.
Anterior horn (C) is poliomyelitis. Microvascular occlusion (D) occurs in vasculitic
neuropathy, not GBS.
