WGU D115 Advanced Pathophysiology for APRN
Objective Assessment (OA) Practice Simulation -
2026-2027 Academic Year | Advanced Practice
Competency
Items: 70 | Format: integrated, single-best-answer (plus 6 SATA) | Target: “Graded A”
readiness
1. A 38-year-old G2P1 at 18 weeks’ gestation is found to have a fetus with trisomy 21
confirmed by cell-free DNA and amniocentesis. Which meiotic error and molecular
karyotype best explain the pathogenesis?
A. Meiosis-I nondisjunction 46,XX,dup(21q22.3)
B. Meiosis-II nondisjunction 47,XX,+21
C. Robertsonian translocation 46,XX,der(14;21)(q10;q10),+21
D. De novo deletion 46,XY,del(21)(q11.2)
Verified Answer: C
Rationale: Robertsonian translocation between acrocentric chromosomes 14 and 21
produces a 46-count karyotype with functional gain of 21q material—classic heritable
mechanism; APRN must recognize recurrence risk in future pregnancies versus meiotic
nondisjunction.
,2. (SATA) A 55-year-old male with NYHA class III HFpEF (EF 55 %) develops worsening
dyspnea. Echo shows grade-II diastolic dysfunction, LA volume index 45 mL/m², TR
velocity 3.2 m/s. Which cellular/molecular mechanisms underlie his pathophysiology?
(Select all.)
A. Titin hypophosphorylation ↑ passive stiffness
B. Interstitial collagen cross-linking by AGEs
C. Serca2a up-regulation accelerating relaxation
D. Increased myocardial endothelial NO synthase activity
E. Systemic inflammation with IL-6–mediated fibroblast activation
Verified Answers: A, B, E
Rationale: HFpEF is driven by increased ventricular stiffness (A, B) and pro-fibrotic
inflammation (E). Serca2a up-regulation (C) and ↑ NO (D) would enhance—not
impair—relaxation.
3. A 29-year-old woman presents with recurrent calcium oxalate nephrolithiasis,
osteoporosis, and fatigue. Labs: Ca²⁺ 8.1 mg/dL (↓), PO₄ 2.0 mg/dL (↓), PTH 110 pg/mL
(↑↑), 1,25-(OH)₂-vitamin D low-normal. Which underlying defect explains this
constellation?
A. Autosomal-dominant gain-of-function CASR mutation
B. CYP24A1 loss-of-function causing 24-hydroxylase deficiency
C. Impaired renal 1-α-hydroxylase in CKD stage IV
D. Post-surgical hypoparathyroidism
,Verified Answer: A
Rationale: Activating CASR lowers calcium set-point → hypocalcemia,
hyperphosphaturia, and compensatory ↑ PTH; APRN links biochemical pattern to
molecular defect.
4. A patient with CLL receives ibrutinib and 4 weeks later develops new-onset atrial
fibrillation. Which kinase pathway inhibition is most directly responsible?
A. PI3Kδ → impaired B-cell survival
B. BTK → PLCγ2 → reduced ventricular PI3K-Akt
C. BTK → Tec-family off-target effects on cardiac myocyte calcium handling
D. SYK inhibition → platelet adhesion defect
Verified Answer: C
Rationale: Ibrutinib blocks BTK but also inhibits Tec kinases in cardiomyocytes,
disrupting Ca²⁺ signaling and precipitating AF—core advanced pharmacogenomics
concept.
5. A 64-year-old man with T2DM, HTN, BMI 34 kg/m² has hs-CRP 8 mg/L, HDL-C 30
mg/dL, triglycerides 260 mg/dL. Which integrative pathway best links his insulin
resistance to systemic CVD risk?
A. IRS-1 serine phosphorylation → impaired NO production → endothelial dysfunction
B. GLUT-4 up-regulation → hyperinsulinemia → plaque stabilization
C. AMPK activation → ↓ VLDL synthesis
D. Adiponectin surge → macrophage M1 polarization
, Verified Answer: A
Rationale: IRS-1 serine phosphorylation uncouples insulin signaling and PI3K-Akt–eNOS
arm, reducing NO bioavailability—mechanistic bridge between metabolic syndrome and
atherosclerosis.
6. (SATA) A 19-year-old female with SLE develops sudden left-leg weakness. MRI shows
multiple subcortical hyperintensities; CSF is normal. Which pathophysiologic
mechanisms support a diagnosis of neuropsychiatric lupus? (Select all.)
A. Anti-ribosomal P cross-reactivity with neuronal surface antigens
B. Complement C5a-mediated microangiopathy
C. Type-I interferon–driven microglial activation
D. Anti-SSA/Ro triggering oligodendrocyte apoptosis
E. Aquaporin-4 autoantibody production
Verified Answers: A, B, C
Rationale: Anti-ribosomal P (A), complement activation (B), and IFN-α (C) are
established CNS lupus drivers. Anti-SSA (D) associates with neonatal lupus;
aquaporin-4 (E) defines NMO, not NPSLE.
7. A 48-hour-old neonate with trisomy 21 becomes tachypneic and hypoxemic. CXR
shows increased pulmonary vascular markings and cardiomegaly. Which embryologic
defect and shunt direction are responsible?
A. Distal coronary sinus fistula; left-to-right
B. Endocardial cushion defect (AVSD); left-to-right
Objective Assessment (OA) Practice Simulation -
2026-2027 Academic Year | Advanced Practice
Competency
Items: 70 | Format: integrated, single-best-answer (plus 6 SATA) | Target: “Graded A”
readiness
1. A 38-year-old G2P1 at 18 weeks’ gestation is found to have a fetus with trisomy 21
confirmed by cell-free DNA and amniocentesis. Which meiotic error and molecular
karyotype best explain the pathogenesis?
A. Meiosis-I nondisjunction 46,XX,dup(21q22.3)
B. Meiosis-II nondisjunction 47,XX,+21
C. Robertsonian translocation 46,XX,der(14;21)(q10;q10),+21
D. De novo deletion 46,XY,del(21)(q11.2)
Verified Answer: C
Rationale: Robertsonian translocation between acrocentric chromosomes 14 and 21
produces a 46-count karyotype with functional gain of 21q material—classic heritable
mechanism; APRN must recognize recurrence risk in future pregnancies versus meiotic
nondisjunction.
,2. (SATA) A 55-year-old male with NYHA class III HFpEF (EF 55 %) develops worsening
dyspnea. Echo shows grade-II diastolic dysfunction, LA volume index 45 mL/m², TR
velocity 3.2 m/s. Which cellular/molecular mechanisms underlie his pathophysiology?
(Select all.)
A. Titin hypophosphorylation ↑ passive stiffness
B. Interstitial collagen cross-linking by AGEs
C. Serca2a up-regulation accelerating relaxation
D. Increased myocardial endothelial NO synthase activity
E. Systemic inflammation with IL-6–mediated fibroblast activation
Verified Answers: A, B, E
Rationale: HFpEF is driven by increased ventricular stiffness (A, B) and pro-fibrotic
inflammation (E). Serca2a up-regulation (C) and ↑ NO (D) would enhance—not
impair—relaxation.
3. A 29-year-old woman presents with recurrent calcium oxalate nephrolithiasis,
osteoporosis, and fatigue. Labs: Ca²⁺ 8.1 mg/dL (↓), PO₄ 2.0 mg/dL (↓), PTH 110 pg/mL
(↑↑), 1,25-(OH)₂-vitamin D low-normal. Which underlying defect explains this
constellation?
A. Autosomal-dominant gain-of-function CASR mutation
B. CYP24A1 loss-of-function causing 24-hydroxylase deficiency
C. Impaired renal 1-α-hydroxylase in CKD stage IV
D. Post-surgical hypoparathyroidism
,Verified Answer: A
Rationale: Activating CASR lowers calcium set-point → hypocalcemia,
hyperphosphaturia, and compensatory ↑ PTH; APRN links biochemical pattern to
molecular defect.
4. A patient with CLL receives ibrutinib and 4 weeks later develops new-onset atrial
fibrillation. Which kinase pathway inhibition is most directly responsible?
A. PI3Kδ → impaired B-cell survival
B. BTK → PLCγ2 → reduced ventricular PI3K-Akt
C. BTK → Tec-family off-target effects on cardiac myocyte calcium handling
D. SYK inhibition → platelet adhesion defect
Verified Answer: C
Rationale: Ibrutinib blocks BTK but also inhibits Tec kinases in cardiomyocytes,
disrupting Ca²⁺ signaling and precipitating AF—core advanced pharmacogenomics
concept.
5. A 64-year-old man with T2DM, HTN, BMI 34 kg/m² has hs-CRP 8 mg/L, HDL-C 30
mg/dL, triglycerides 260 mg/dL. Which integrative pathway best links his insulin
resistance to systemic CVD risk?
A. IRS-1 serine phosphorylation → impaired NO production → endothelial dysfunction
B. GLUT-4 up-regulation → hyperinsulinemia → plaque stabilization
C. AMPK activation → ↓ VLDL synthesis
D. Adiponectin surge → macrophage M1 polarization
, Verified Answer: A
Rationale: IRS-1 serine phosphorylation uncouples insulin signaling and PI3K-Akt–eNOS
arm, reducing NO bioavailability—mechanistic bridge between metabolic syndrome and
atherosclerosis.
6. (SATA) A 19-year-old female with SLE develops sudden left-leg weakness. MRI shows
multiple subcortical hyperintensities; CSF is normal. Which pathophysiologic
mechanisms support a diagnosis of neuropsychiatric lupus? (Select all.)
A. Anti-ribosomal P cross-reactivity with neuronal surface antigens
B. Complement C5a-mediated microangiopathy
C. Type-I interferon–driven microglial activation
D. Anti-SSA/Ro triggering oligodendrocyte apoptosis
E. Aquaporin-4 autoantibody production
Verified Answers: A, B, C
Rationale: Anti-ribosomal P (A), complement activation (B), and IFN-α (C) are
established CNS lupus drivers. Anti-SSA (D) associates with neonatal lupus;
aquaporin-4 (E) defines NMO, not NPSLE.
7. A 48-hour-old neonate with trisomy 21 becomes tachypneic and hypoxemic. CXR
shows increased pulmonary vascular markings and cardiomegaly. Which embryologic
defect and shunt direction are responsible?
A. Distal coronary sinus fistula; left-to-right
B. Endocardial cushion defect (AVSD); left-to-right
