NUR 5461 Module 5 Quiz - Advanced
Pathophysiology - (2026) Actual Questions & Answers
(William Paterson University
1. A research study investigates the role of hypoxia-inducible factor 1 (HIF-1) in cellular
adaptation. Under normoxic conditions, HIF-1 is hydroxylated by prolyl hydroxylase domain
(PHD) enzymes and targeted for proteasomal degradation via von Hippel-Lindau (VHL) protein.
In a cell line with a homozygous loss-of-function mutation in VHL, which of the following
outcomes is most likely to be observed despite normal oxygen tension?
A. Decreased expression of vascular endothelial growth factor (VEGF) and erythropoietin (EPO)
B. Constitutive stabilization of HIF-1 leading to increased transcription of glycolytic enzymes and angiogenic
factors
C. Accumulation of reactive oxygen species (ROS) due to impaired mitochondrial electron transport
D. Enhanced apoptosis via p53-mediated pathways
Answer: B
Rationale: VHL protein is required for ubiquitination and degradation of HIF-1±. Loss of VHL prevents
HIF-1 degradation, leading to its accumulation even in normoxia. Stabilized HIF-1 translocates to the
nucleus and upregulates target genes such as VEGF, EPO, and glycolytic enzymes. Option A is opposite;
C and D are not direct consequences of VHL loss.
2. In a patient with decompensated cirrhosis, the development of hepatorenal syndrome (HRS) is
driven by splanchnic vasodilation and renal vasoconstriction. Which of the following best explains
the role of the renin-angiotensin-aldosterone system (RAAS) in this pathophysiology?
A. RAAS activation is suppressed due to increased renal perfusion pressure from systemic vasodilation
B. Angiotensin II contributes to renal vasoconstriction but aldosterone-mediated sodium retention worsens
ascites
C. RAAS activation is blunted by elevated levels of atrial natriuretic peptide (ANP) from portal hypertension
D. Angiotensin II directly stimulates splanchnic vasodilation via AT2 receptors
Answer: B
Rationale: In cirrhosis, splanchnic vasodilation reduces effective arterial blood volume, activating RAAS.
Angiotensin II constricts renal arterioles, reducing GFR, while aldosterone increases sodium and water
retention, exacerbating ascites. Option A is incorrect because renal perfusion is decreased; C is false
because ANP is often elevated but cannot override RAAS; D is wrong because angiotensin II causes
vasoconstriction, not vasodilation.
Page 1
,3. A 45-year-old individual with a history of recurrent deep vein thrombosis and pulmonary
embolism is found to have a normal activated partial thromboplastin time (aPTT) and
prothrombin time (PT), but elevated D-dimer. Further testing reveals a mutation in the
prothrombin gene (G20210A). Which of the following best describes the mechanism by which this
mutation increases thrombotic risk?
A. Increased synthesis of prothrombin leading to enhanced thrombin generation
B. Resistance to activated protein C (APC) due to altered cleavage site on factor Va
C. Decreased antithrombin III activity due to impaired binding to heparin-like molecules
D. Impaired fibrinolysis due to elevated plasminogen activator inhibitor-1 (PAI-1)
Answer: A
Rationale: The prothrombin G20210A mutation is a gain-of-function polymorphism in the 3'-untranslated
region of the prothrombin gene, resulting in increased mRNA stability and higher plasma prothrombin
levels. This leads to increased thrombin generation and a hypercoagulable state. Option B describes
factor V Leiden; C and D are not associated with this mutation.
4. A patient with septic shock develops disseminated intravascular coagulation (DIC). Laboratory
findings show prolonged PT and aPTT, low fibrinogen, elevated D-dimer, and thrombocytopenia.
Which of the following is the primary mechanism driving the coagulopathy in this scenario?
A. Excessive activation of protein C and protein S leading to consumption of coagulation factors
B. Widespread endothelial injury triggering tissue factor expression and uncontrolled thrombin generation
C. Primary fibrinolysis due to release of tissue plasminogen activator (tPA) from damaged endothelium
D. Autoantibody-mediated inhibition of factor VIII activity
Answer: B
Rationale: In sepsis, endothelial injury and inflammatory cytokines induce tissue factor expression on
monocytes and endothelial cells, activating the extrinsic coagulation pathway. This leads to widespread
thrombin generation, consumption of clotting factors and platelets, and secondary fibrinolysis. Option A
is incorrect because protein C is consumed, not excessively activated; C is secondary, not primary; D
describes acquired hemophilia.
5. A researcher is studying a novel oncogene that encodes a receptor tyrosine kinase (RTK). In a
subset of tumors, a point mutation in the RTK's transmembrane domain leads to constitutive
dimerization and activation independent of ligand binding. Which of the following downstream
signaling pathways is most likely to be persistently activated, thereby promoting cell proliferation
and survival?
A. JAK-STAT pathway via phosphorylation of STAT3
B. RAS-RAF-MEK-ERK pathway via activation of SOS and GRB2
C. PI3K-AKT-mTOR pathway via activation of PI3K
D. Wnt--catenin pathway via inhibition of GSK-3
Answer: B
Rationale: Constitutively active RTKs typically recruit adaptor proteins such as GRB2 and SOS, which
activate RAS. RAS then triggers the RAF-MEK-ERK cascade, promoting cell proliferation. While
PI3K-AKT (C) can also be activated, the RAS-RAF-MEK-ERK pathway is the classic downstream
effector of RTK signaling. JAK-STAT (A) is associated with cytokine receptors; Wnt (D) is not directly
activated by RTKs.
Page 2
,6. In a patient with chronic myeloid leukemia (CML), the BCR-ABL fusion protein exhibits
constitutive tyrosine kinase activity. Imatinib, a tyrosine kinase inhibitor, binds to the ATP-binding
site of BCR-ABL and inhibits its activity. However, some patients develop resistance due to a point
mutation in the kinase domain that prevents imatinib binding but does not affect ATP binding.
Which of the following best explains why this mutation allows continued leukemogenesis?
A. The mutation enhances the affinity of BCR-ABL for ATP, overcoming inhibition
B. The mutation stabilizes the active conformation of BCR-ABL, reducing the need for ATP
C. The mutation prevents imatinib from binding while preserving ATP binding and kinase activity
D. The mutation activates an alternative signaling pathway that bypasses BCR-ABL
Answer: C
Rationale: Imatinib competes with ATP for binding to the BCR-ABL kinase domain. A mutation that
alters the binding site for imatinib but not for ATP allows the kinase to remain active even in the
presence of the drug, as ATP can still bind and be utilized. Options A and B are not typical; D is not the
primary mechanism.
7. A patient with severe sepsis develops acute respiratory distress syndrome (ARDS). The
pathophysiology includes diffuse alveolar damage, increased pulmonary vascular permeability,
and formation of hyaline membranes. Which of the following mechanisms is most directly
responsible for the formation of hyaline membranes?
A. Deposition of fibrin and cellular debris in alveolar spaces due to protein-rich edema fluid
B. Proliferation of type II pneumocytes and secretion of surfactant proteins
C. Hyalinization of the alveolar basement membrane due to collagen deposition
D. Accumulation of neutrophils and macrophages in the interstitium
Answer: A
Rationale: Hyaline membranes are composed of fibrin, plasma proteins, and necrotic cellular debris that
line the alveolar walls. They result from the exudation of protein-rich fluid into the alveolar spaces due
to increased capillary permeability. Option B describes repair; C is not typical; D is part of the
inflammatory response but not the direct cause of hyaline membranes.
8. A patient with a history of chronic alcoholism presents with jaundice, ascites, and coagulopathy.
Laboratory tests reveal elevated serum bilirubin (direct and indirect), prolonged PT, low albumin,
and elevated ammonia. Which of the following best explains the pathogenesis of the coagulopathy
in this patient?
A. Decreased synthesis of vitamin K-dependent clotting factors due to hepatocellular dysfunction
B. Increased consumption of clotting factors due to chronic disseminated intravascular coagulation
C. Impaired absorption of vitamin K due to bile salt deficiency from cholestasis
D. Enhanced fibrinolysis due to decreased hepatic clearance of tissue plasminogen activator
Answer: A
Rationale: The liver synthesizes most clotting factors, including vitamin K-dependent factors (II, VII, IX,
X). In chronic liver disease, hepatocellular dysfunction reduces synthesis of these factors, leading to
prolonged PT. Option C is a contributing factor if cholestasis is present, but the primary mechanism is
decreased synthesis. B and D are less significant in this context.
Page 3
, 9. A patient with type 2 diabetes mellitus develops diabetic nephropathy. Renal biopsy shows
nodular glomerulosclerosis (Kimmelstiel-Wilson nodules). Which of the following
pathophysiological processes is most directly responsible for the formation of these nodules?
A. Non-enzymatic glycosylation of glomerular basement membrane proteins leading to increased matrix
deposition
B. Hyperfiltration-induced mechanical stress causing podocyte detachment and focal segmental
glomerulosclerosis
C. Immune complex deposition in the mesangium due to altered glycosylation of immunoglobulins
D. Mesangial cell proliferation and increased production of extracellular matrix components
Answer: D
Rationale: Kimmelstiel-Wilson nodules are acellular, eosinophilic nodules in the mesangium composed of
increased extracellular matrix (collagen, laminin, fibronectin). They result from mesangial cell
activation by hyperglycemia-induced growth factors (e.g., TGF-) leading to matrix overproduction.
Option A contributes to basement membrane thickening but not specifically nodules; B describes other
lesions; C is not a primary mechanism.
10. A patient with a history of recurrent calcium oxalate kidney stones is found to have idiopathic
hypercalciuria. Which of the following is the most likely underlying pathophysiological
mechanism?
A. Increased intestinal absorption of calcium due to elevated 1,25-dihydroxyvitamin D levels
B. Renal phosphate leak leading to secondary hyperparathyroidism and increased bone resorption
C. Distal renal tubular acidosis causing alkaline urine and calcium phosphate precipitation
D. Increased renal excretion of calcium due to a defect in tubular reabsorption
Answer: A
Rationale: The most common cause of idiopathic hypercalciuria is increased intestinal calcium
absorption, often due to mildly elevated 1,25-dihydroxyvitamin D levels or increased sensitivity to
vitamin D. This leads to hypercalciuria and stone formation. Option B describes phosphate wasting; C
causes calcium phosphate stones; D is a less common mechanism.
11. A 45-year-old individual with a history of chronic kidney disease (stage 3) presents with fatigue,
muscle cramps, and an ECG showing prolonged QT interval. Lab results reveal serum potassium
of 6.8 mEq/L and serum calcium of 8.0 mg/dL. Which of the following pathophysiological
mechanisms best explains the ECG abnormality?
A. Hyperkalemia-induced accelerated repolarization due to increased extracellular potassium gradient across
myocardial cells
B. Hypocalcemia-induced prolongation of the plateau phase of the cardiac action potential, exacerbated by
hyperkalemia
C. Hyperkalemia-induced depolarization block due to reduced resting membrane potential, leading to slowed
conduction
D. Hypocalcemia-induced shortening of the action potential duration, counteracting hyperkalemic effects
Answer: B
Rationale: Prolonged QT interval in this setting is primarily due to hypocalcemia, which prolongs the
plateau phase (phase 2) of the cardiac action potential by reducing calcium influx. Hyperkalemia
typically causes peaked T waves and widened QRS, not QT prolongation. The combination of
Page 4
Pathophysiology - (2026) Actual Questions & Answers
(William Paterson University
1. A research study investigates the role of hypoxia-inducible factor 1 (HIF-1) in cellular
adaptation. Under normoxic conditions, HIF-1 is hydroxylated by prolyl hydroxylase domain
(PHD) enzymes and targeted for proteasomal degradation via von Hippel-Lindau (VHL) protein.
In a cell line with a homozygous loss-of-function mutation in VHL, which of the following
outcomes is most likely to be observed despite normal oxygen tension?
A. Decreased expression of vascular endothelial growth factor (VEGF) and erythropoietin (EPO)
B. Constitutive stabilization of HIF-1 leading to increased transcription of glycolytic enzymes and angiogenic
factors
C. Accumulation of reactive oxygen species (ROS) due to impaired mitochondrial electron transport
D. Enhanced apoptosis via p53-mediated pathways
Answer: B
Rationale: VHL protein is required for ubiquitination and degradation of HIF-1±. Loss of VHL prevents
HIF-1 degradation, leading to its accumulation even in normoxia. Stabilized HIF-1 translocates to the
nucleus and upregulates target genes such as VEGF, EPO, and glycolytic enzymes. Option A is opposite;
C and D are not direct consequences of VHL loss.
2. In a patient with decompensated cirrhosis, the development of hepatorenal syndrome (HRS) is
driven by splanchnic vasodilation and renal vasoconstriction. Which of the following best explains
the role of the renin-angiotensin-aldosterone system (RAAS) in this pathophysiology?
A. RAAS activation is suppressed due to increased renal perfusion pressure from systemic vasodilation
B. Angiotensin II contributes to renal vasoconstriction but aldosterone-mediated sodium retention worsens
ascites
C. RAAS activation is blunted by elevated levels of atrial natriuretic peptide (ANP) from portal hypertension
D. Angiotensin II directly stimulates splanchnic vasodilation via AT2 receptors
Answer: B
Rationale: In cirrhosis, splanchnic vasodilation reduces effective arterial blood volume, activating RAAS.
Angiotensin II constricts renal arterioles, reducing GFR, while aldosterone increases sodium and water
retention, exacerbating ascites. Option A is incorrect because renal perfusion is decreased; C is false
because ANP is often elevated but cannot override RAAS; D is wrong because angiotensin II causes
vasoconstriction, not vasodilation.
Page 1
,3. A 45-year-old individual with a history of recurrent deep vein thrombosis and pulmonary
embolism is found to have a normal activated partial thromboplastin time (aPTT) and
prothrombin time (PT), but elevated D-dimer. Further testing reveals a mutation in the
prothrombin gene (G20210A). Which of the following best describes the mechanism by which this
mutation increases thrombotic risk?
A. Increased synthesis of prothrombin leading to enhanced thrombin generation
B. Resistance to activated protein C (APC) due to altered cleavage site on factor Va
C. Decreased antithrombin III activity due to impaired binding to heparin-like molecules
D. Impaired fibrinolysis due to elevated plasminogen activator inhibitor-1 (PAI-1)
Answer: A
Rationale: The prothrombin G20210A mutation is a gain-of-function polymorphism in the 3'-untranslated
region of the prothrombin gene, resulting in increased mRNA stability and higher plasma prothrombin
levels. This leads to increased thrombin generation and a hypercoagulable state. Option B describes
factor V Leiden; C and D are not associated with this mutation.
4. A patient with septic shock develops disseminated intravascular coagulation (DIC). Laboratory
findings show prolonged PT and aPTT, low fibrinogen, elevated D-dimer, and thrombocytopenia.
Which of the following is the primary mechanism driving the coagulopathy in this scenario?
A. Excessive activation of protein C and protein S leading to consumption of coagulation factors
B. Widespread endothelial injury triggering tissue factor expression and uncontrolled thrombin generation
C. Primary fibrinolysis due to release of tissue plasminogen activator (tPA) from damaged endothelium
D. Autoantibody-mediated inhibition of factor VIII activity
Answer: B
Rationale: In sepsis, endothelial injury and inflammatory cytokines induce tissue factor expression on
monocytes and endothelial cells, activating the extrinsic coagulation pathway. This leads to widespread
thrombin generation, consumption of clotting factors and platelets, and secondary fibrinolysis. Option A
is incorrect because protein C is consumed, not excessively activated; C is secondary, not primary; D
describes acquired hemophilia.
5. A researcher is studying a novel oncogene that encodes a receptor tyrosine kinase (RTK). In a
subset of tumors, a point mutation in the RTK's transmembrane domain leads to constitutive
dimerization and activation independent of ligand binding. Which of the following downstream
signaling pathways is most likely to be persistently activated, thereby promoting cell proliferation
and survival?
A. JAK-STAT pathway via phosphorylation of STAT3
B. RAS-RAF-MEK-ERK pathway via activation of SOS and GRB2
C. PI3K-AKT-mTOR pathway via activation of PI3K
D. Wnt--catenin pathway via inhibition of GSK-3
Answer: B
Rationale: Constitutively active RTKs typically recruit adaptor proteins such as GRB2 and SOS, which
activate RAS. RAS then triggers the RAF-MEK-ERK cascade, promoting cell proliferation. While
PI3K-AKT (C) can also be activated, the RAS-RAF-MEK-ERK pathway is the classic downstream
effector of RTK signaling. JAK-STAT (A) is associated with cytokine receptors; Wnt (D) is not directly
activated by RTKs.
Page 2
,6. In a patient with chronic myeloid leukemia (CML), the BCR-ABL fusion protein exhibits
constitutive tyrosine kinase activity. Imatinib, a tyrosine kinase inhibitor, binds to the ATP-binding
site of BCR-ABL and inhibits its activity. However, some patients develop resistance due to a point
mutation in the kinase domain that prevents imatinib binding but does not affect ATP binding.
Which of the following best explains why this mutation allows continued leukemogenesis?
A. The mutation enhances the affinity of BCR-ABL for ATP, overcoming inhibition
B. The mutation stabilizes the active conformation of BCR-ABL, reducing the need for ATP
C. The mutation prevents imatinib from binding while preserving ATP binding and kinase activity
D. The mutation activates an alternative signaling pathway that bypasses BCR-ABL
Answer: C
Rationale: Imatinib competes with ATP for binding to the BCR-ABL kinase domain. A mutation that
alters the binding site for imatinib but not for ATP allows the kinase to remain active even in the
presence of the drug, as ATP can still bind and be utilized. Options A and B are not typical; D is not the
primary mechanism.
7. A patient with severe sepsis develops acute respiratory distress syndrome (ARDS). The
pathophysiology includes diffuse alveolar damage, increased pulmonary vascular permeability,
and formation of hyaline membranes. Which of the following mechanisms is most directly
responsible for the formation of hyaline membranes?
A. Deposition of fibrin and cellular debris in alveolar spaces due to protein-rich edema fluid
B. Proliferation of type II pneumocytes and secretion of surfactant proteins
C. Hyalinization of the alveolar basement membrane due to collagen deposition
D. Accumulation of neutrophils and macrophages in the interstitium
Answer: A
Rationale: Hyaline membranes are composed of fibrin, plasma proteins, and necrotic cellular debris that
line the alveolar walls. They result from the exudation of protein-rich fluid into the alveolar spaces due
to increased capillary permeability. Option B describes repair; C is not typical; D is part of the
inflammatory response but not the direct cause of hyaline membranes.
8. A patient with a history of chronic alcoholism presents with jaundice, ascites, and coagulopathy.
Laboratory tests reveal elevated serum bilirubin (direct and indirect), prolonged PT, low albumin,
and elevated ammonia. Which of the following best explains the pathogenesis of the coagulopathy
in this patient?
A. Decreased synthesis of vitamin K-dependent clotting factors due to hepatocellular dysfunction
B. Increased consumption of clotting factors due to chronic disseminated intravascular coagulation
C. Impaired absorption of vitamin K due to bile salt deficiency from cholestasis
D. Enhanced fibrinolysis due to decreased hepatic clearance of tissue plasminogen activator
Answer: A
Rationale: The liver synthesizes most clotting factors, including vitamin K-dependent factors (II, VII, IX,
X). In chronic liver disease, hepatocellular dysfunction reduces synthesis of these factors, leading to
prolonged PT. Option C is a contributing factor if cholestasis is present, but the primary mechanism is
decreased synthesis. B and D are less significant in this context.
Page 3
, 9. A patient with type 2 diabetes mellitus develops diabetic nephropathy. Renal biopsy shows
nodular glomerulosclerosis (Kimmelstiel-Wilson nodules). Which of the following
pathophysiological processes is most directly responsible for the formation of these nodules?
A. Non-enzymatic glycosylation of glomerular basement membrane proteins leading to increased matrix
deposition
B. Hyperfiltration-induced mechanical stress causing podocyte detachment and focal segmental
glomerulosclerosis
C. Immune complex deposition in the mesangium due to altered glycosylation of immunoglobulins
D. Mesangial cell proliferation and increased production of extracellular matrix components
Answer: D
Rationale: Kimmelstiel-Wilson nodules are acellular, eosinophilic nodules in the mesangium composed of
increased extracellular matrix (collagen, laminin, fibronectin). They result from mesangial cell
activation by hyperglycemia-induced growth factors (e.g., TGF-) leading to matrix overproduction.
Option A contributes to basement membrane thickening but not specifically nodules; B describes other
lesions; C is not a primary mechanism.
10. A patient with a history of recurrent calcium oxalate kidney stones is found to have idiopathic
hypercalciuria. Which of the following is the most likely underlying pathophysiological
mechanism?
A. Increased intestinal absorption of calcium due to elevated 1,25-dihydroxyvitamin D levels
B. Renal phosphate leak leading to secondary hyperparathyroidism and increased bone resorption
C. Distal renal tubular acidosis causing alkaline urine and calcium phosphate precipitation
D. Increased renal excretion of calcium due to a defect in tubular reabsorption
Answer: A
Rationale: The most common cause of idiopathic hypercalciuria is increased intestinal calcium
absorption, often due to mildly elevated 1,25-dihydroxyvitamin D levels or increased sensitivity to
vitamin D. This leads to hypercalciuria and stone formation. Option B describes phosphate wasting; C
causes calcium phosphate stones; D is a less common mechanism.
11. A 45-year-old individual with a history of chronic kidney disease (stage 3) presents with fatigue,
muscle cramps, and an ECG showing prolonged QT interval. Lab results reveal serum potassium
of 6.8 mEq/L and serum calcium of 8.0 mg/dL. Which of the following pathophysiological
mechanisms best explains the ECG abnormality?
A. Hyperkalemia-induced accelerated repolarization due to increased extracellular potassium gradient across
myocardial cells
B. Hypocalcemia-induced prolongation of the plateau phase of the cardiac action potential, exacerbated by
hyperkalemia
C. Hyperkalemia-induced depolarization block due to reduced resting membrane potential, leading to slowed
conduction
D. Hypocalcemia-induced shortening of the action potential duration, counteracting hyperkalemic effects
Answer: B
Rationale: Prolonged QT interval in this setting is primarily due to hypocalcemia, which prolongs the
plateau phase (phase 2) of the cardiac action potential by reducing calcium influx. Hyperkalemia
typically causes peaked T waves and widened QRS, not QT prolongation. The combination of
Page 4
