Exam 3: NURS 5315 (Latest 2025/2026 Update)
Advanced Pathophysiology Questions with Verified
Answers | 100% Correct |Graded A- UTA.
1. A patient with a history of chronic venous insufficiency develops a non-healing ulcer on the
medial malleolus. Histological examination of the ulcer base shows abundant granulation tissue
with numerous newly formed capillaries, but the endothelial cells exhibit abnormal pericyte
coverage and increased expression of vascular endothelial growth factor (VEGF). Which of the
following best explains the impaired wound healing in this context?
A. Excessive collagen deposition due to transforming growth factor-beta (TGF-) overactivity
B. Impaired angiogenesis due to reduced hypoxia-inducible factor-1 alpha (HIF-1) stabilization
C. Defective maturation of new vessels leading to increased permeability and edema
D. Overexpression of matrix metalloproteinases (MMPs) causing basement membrane destruction
Answer: C
Rationale: In chronic venous insufficiency, venous hypertension leads to persistent edema and
microvascular damage. The newly formed capillaries lack adequate pericyte coverage, resulting in leaky
vessels that perpetuate edema and impair healing. While VEGF is elevated, the vessels are immature
and dysfunctional, not deficient. TGF- overactivity would cause fibrosis, not impaired healing. HIF-1 is
typically stabilized in hypoxia, promoting angiogenesis. MMP overexpression can contribute to tissue
breakdown but is not the primary defect in this scenario.
2. A researcher is studying the role of mitochondrial permeability transition pore (mPTP) in
ischemia-reperfusion injury. In an in vitro model of cardiomyocyte hypoxia/reoxygenation,
treatment with cyclosporin A (an mPTP inhibitor) significantly reduces cell death. However, when
the same treatment is applied after prolonged ischemia (60 minutes), the protective effect is lost.
Which of the following best explains this observation?
A. Cyclosporin A becomes cytotoxic after prolonged hypoxia due to accumulation of reactive oxygen species
B. Prolonged ischemia leads to irreversible mPTP opening and cytochrome c release, independent of
cyclosporin A
C. Cyclosporin A inhibits calcineurin, which is required for protective autophagy during prolonged ischemia
D. The mPTP closes spontaneously after 60 minutes, rendering cyclosporin A ineffective
Answer: B
Rationale: During ischemia-reperfusion, mPTP opening is a critical event leading to mitochondrial
dysfunction and cell death. Cyclosporin A inhibits mPTP opening and is protective when administered
early. However, after prolonged ischemia, the mPTP opens irreversibly, leading to release of
cytochrome c and activation of apoptosis, which cannot be reversed by mPTP inhibition. The other
options are not supported by current understanding; cyclosporin A does not become cytotoxic,
calcineurin inhibition is not protective in this context, and mPTP does not close spontaneously.
Page 1
,3. A 45-year-old patient with a history of hypertension and type 2 diabetes presents with sudden
onset of severe right flank pain radiating to the groin. Urinalysis shows hematuria and pH 6.5. A
non-contrast CT reveals a 5 mm calculus in the proximal ureter. The stone is composed of calcium
oxalate monohydrate. Which of the following urinary abnormalities is most likely contributing to
stone formation in this patient?
A. Low urinary citrate concentration
B. High urinary magnesium concentration
C. High urinary pH above 7.0
D. Low urinary uric acid concentration
Answer: A
Rationale: Calcium oxalate stones form when urine is supersaturated with calcium and oxalate. Citrate is
a natural inhibitor of stone formation because it binds calcium and reduces supersaturation. Low
urinary citrate (hypocitraturia) is a common risk factor, especially in patients with metabolic acidosis
(e.g., from diabetes or hypertension). High magnesium would inhibit stone formation. High pH (>7.0)
favors calcium phosphate stones, not calcium oxalate. Low uric acid is not directly related to calcium
oxalate stones; hyperuricosuria can promote calcium oxalate stones via heterogeneous nucleation.
4. A 60-year-old patient with a 30-pack-year smoking history presents with hemoptysis and weight
loss. Chest CT shows a 3 cm mass in the right upper lobe. Biopsy reveals small cell lung carcinoma.
Genetic analysis shows a mutation in the RB1 gene and loss of heterozygosity on chromosome 3p.
Which of the following additional molecular alterations is most likely to be present in this tumor?
A. EGFR activating mutation
B. ALK gene rearrangement
C. MYC amplification
D. KRAS mutation
Answer: C
Rationale: Small cell lung carcinoma (SCLC) is strongly associated with RB1 loss and 3p deletion. MYC
amplification is a common event in SCLC, contributing to its aggressive growth. EGFR mutations and
ALK rearrangements are typical of non-small cell lung cancer (NSCLC), especially adenocarcinoma.
KRAS mutations are also more common in NSCLC, particularly in smokers, but not characteristic of
SCLC. Therefore, MYC amplification is the most likely additional alteration.
5. A researcher is investigating the role of the complement system in a mouse model of sepsis. Mice
deficient in C3 show improved survival compared to wild-type mice after cecal ligation and
puncture. However, when these C3-deficient mice are also deficient in factor B, survival returns to
wild-type levels. Which of the following best explains this observation?
A. C3 deficiency prevents formation of the membrane attack complex, but factor B deficiency restores it via the
lectin pathway
B. C3 deficiency leads to uncontrolled activation of the alternative pathway, which is prevented by factor B
deficiency
C. Factor B deficiency impairs opsonization, compensating for the loss of C3
D. C3 deficiency increases production of C5a, which is toxic; factor B deficiency reduces C5a
Answer: B
Page 2
,Rationale: C3 is a central component of all complement pathways. In C3 deficiency, the alternative pathway cannot be
properly regulated because C3 is needed for feedback amplification. This leads to uncontrolled activation of the alternative
pathway via the C3b-dependent convertase, consuming complement components and causing excessive inflammation. Factor
B is essential for the alternative pathway; its deficiency prevents this uncontrolled activation, restoring survival. The other
options are incorrect: MAC formation is not restored by factor B deficiency; opsonization is impaired in both; C5a levels are
not increased by C3 deficiency.
6. A 50-year-old patient with chronic kidney disease (stage 4) presents with bone pain and a
pathological fracture of the femur. Laboratory studies show: serum calcium 8.2 mg/dL, phosphate
5.5 mg/dL, intact PTH 250 pg/mL (elevated), 25-hydroxyvitamin D 20 ng/mL (low normal), and
1,25-dihydroxyvitamin D 15 pg/mL (low). Which of the following best describes the pathogenesis of
the bone disease in this patient?
A. Osteomalacia due to vitamin D deficiency from impaired renal hydroxylation
B. Osteitis fibrosa cystica due to secondary hyperparathyroidism
C. Adynamic bone disease due to oversuppression of PTH
D. Osteoporosis due to corticosteroid therapy
Answer: B
Rationale: In chronic kidney disease, hyperphosphatemia and low 1,25-dihydroxyvitamin D stimulate
PTH secretion (secondary hyperparathyroidism). Elevated PTH increases bone turnover, leading to
osteitis fibrosa cystica, characterized by bone pain, fractures, and subperiosteal resorption. The low
1,25-dihydroxyvitamin D is due to impaired 1-hydroxylase activity in the kidney. While vitamin D
deficiency contributes, the predominant lesion is high-turnover bone disease from hyperparathyroidism.
Adynamic bone disease is associated with low PTH, not elevated. Osteoporosis is not the primary
diagnosis.
7. A 35-year-old patient with a family history of breast cancer undergoes genetic testing and is
found to have a pathogenic variant in the BRCA1 gene. The patient asks about the increased risk
for other cancers. Which of the following cancers is this patient at highest risk for beyond breast
cancer?
A. Colorectal cancer
B. Pancreatic cancer
C. Ovarian cancer
D. Prostate cancer
Answer: C
Rationale: BRCA1 mutations confer a high risk of ovarian cancer (up to 40-60% lifetime risk). While
there is also increased risk for pancreatic and prostate cancers, the most significant and
well-established risk after breast cancer is ovarian cancer. Colorectal cancer is not strongly associated
with BRCA1 mutations. Therefore, ovarian cancer is the correct answer.
8. A patient with decompensated cirrhosis develops tense ascites. Paracentesis yields clear fluid
with a serum-ascites albumin gradient (SAAG) of 1.5 g/dL. The fluid total protein is 1.8 g/dL, and
the white blood cell count is 150 cells/L with 60% lymphocytes. Which of the following is the most
likely cause of the ascites?
Page 3
, A. Peritoneal carcinomatosis
B. Tuberculous peritonitis
C. Portal hypertension due to cirrhosis
D. Nephrotic syndrome
Answer: C
Rationale: A SAAG "e1.1 g/dL indicates portal hypertension as the cause of ascites. The low total protein
(<2.5 g/dL) is consistent with cirrhosis, where the hepatic sinusoids are capillarized, allowing
low-protein fluid to leak. Peritoneal carcinomatosis and tuberculous peritonitis typically cause exudative
ascites with SAAG <1.1 and high protein. Nephrotic syndrome can cause ascites but with SAAG <1.1
and high protein. The lymphocytic predominance is non-specific and can be seen in cirrhosis. Thus,
portal hypertension is the most likely.
9. A 55-year-old patient with a history of chronic hepatitis C develops jaundice and abdominal
pain. Laboratory results show: total bilirubin 8.5 mg/dL (direct 6.2), alkaline phosphatase 450 U/L
(elevated), AST 120 U/L, ALT 90 U/L. Ultrasound reveals dilated intrahepatic bile ducts. A CT
scan shows a mass at the hilum of the liver. Biopsy of the mass shows well-formed glands with
abundant desmoplastic stroma. Immunohistochemistry is positive for CK7 and negative for CK20.
Which of the following is the most likely diagnosis?
A. Hepatocellular carcinoma
B. Cholangiocarcinoma
C. Metastatic colorectal adenocarcinoma
D. Gallbladder carcinoma
Answer: B
Rationale: The clinical presentation of obstructive jaundice with dilated intrahepatic ducts and a hilar
mass is classic for perihilar cholangiocarcinoma (Klatskin tumor). Histology shows glands with
desmoplasia, and immunohistochemistry (CK7+/CK20-) is typical of cholangiocarcinoma.
Hepatocellular carcinoma would not cause bile duct obstruction and is usually CK7-/CK20-. Metastatic
colorectal cancer is CK7-/CK20+. Gallbladder carcinoma would present with a mass in the gallbladder
fossa, not hilar.
10. A 40-year-old patient with a history of recurrent deep vein thrombosis and pulmonary
embolism is found to have a prolonged activated partial thromboplastin time (aPTT) that does not
correct with mixing studies. Further testing shows elevated levels of anti-cardiolipin antibodies.
Which of the following mechanisms best explains the thrombotic tendency in this patient?
A. Antibody-mediated inhibition of protein C activation
B. Antibody-mediated activation of platelets
C. Antibody-mediated blockade of antithrombin III
D. Antibody-mediated increase in tissue factor expression
Answer: A
Rationale: Antiphospholipid syndrome (APS) is characterized by autoantibodies against
phospholipid-binding proteins. The lupus anticoagulant (a type of antiphospholipid antibody) prolongs
aPTT due to interference with phospholipid-dependent coagulation tests. The thrombotic tendency is
thought to be due to antibodies that inhibit the protein C pathway, reducing the inactivation of factor Va
and VIIIa. Other mechanisms include interference with annexin A5 and activation of endothelial cells.
Page 4
Advanced Pathophysiology Questions with Verified
Answers | 100% Correct |Graded A- UTA.
1. A patient with a history of chronic venous insufficiency develops a non-healing ulcer on the
medial malleolus. Histological examination of the ulcer base shows abundant granulation tissue
with numerous newly formed capillaries, but the endothelial cells exhibit abnormal pericyte
coverage and increased expression of vascular endothelial growth factor (VEGF). Which of the
following best explains the impaired wound healing in this context?
A. Excessive collagen deposition due to transforming growth factor-beta (TGF-) overactivity
B. Impaired angiogenesis due to reduced hypoxia-inducible factor-1 alpha (HIF-1) stabilization
C. Defective maturation of new vessels leading to increased permeability and edema
D. Overexpression of matrix metalloproteinases (MMPs) causing basement membrane destruction
Answer: C
Rationale: In chronic venous insufficiency, venous hypertension leads to persistent edema and
microvascular damage. The newly formed capillaries lack adequate pericyte coverage, resulting in leaky
vessels that perpetuate edema and impair healing. While VEGF is elevated, the vessels are immature
and dysfunctional, not deficient. TGF- overactivity would cause fibrosis, not impaired healing. HIF-1 is
typically stabilized in hypoxia, promoting angiogenesis. MMP overexpression can contribute to tissue
breakdown but is not the primary defect in this scenario.
2. A researcher is studying the role of mitochondrial permeability transition pore (mPTP) in
ischemia-reperfusion injury. In an in vitro model of cardiomyocyte hypoxia/reoxygenation,
treatment with cyclosporin A (an mPTP inhibitor) significantly reduces cell death. However, when
the same treatment is applied after prolonged ischemia (60 minutes), the protective effect is lost.
Which of the following best explains this observation?
A. Cyclosporin A becomes cytotoxic after prolonged hypoxia due to accumulation of reactive oxygen species
B. Prolonged ischemia leads to irreversible mPTP opening and cytochrome c release, independent of
cyclosporin A
C. Cyclosporin A inhibits calcineurin, which is required for protective autophagy during prolonged ischemia
D. The mPTP closes spontaneously after 60 minutes, rendering cyclosporin A ineffective
Answer: B
Rationale: During ischemia-reperfusion, mPTP opening is a critical event leading to mitochondrial
dysfunction and cell death. Cyclosporin A inhibits mPTP opening and is protective when administered
early. However, after prolonged ischemia, the mPTP opens irreversibly, leading to release of
cytochrome c and activation of apoptosis, which cannot be reversed by mPTP inhibition. The other
options are not supported by current understanding; cyclosporin A does not become cytotoxic,
calcineurin inhibition is not protective in this context, and mPTP does not close spontaneously.
Page 1
,3. A 45-year-old patient with a history of hypertension and type 2 diabetes presents with sudden
onset of severe right flank pain radiating to the groin. Urinalysis shows hematuria and pH 6.5. A
non-contrast CT reveals a 5 mm calculus in the proximal ureter. The stone is composed of calcium
oxalate monohydrate. Which of the following urinary abnormalities is most likely contributing to
stone formation in this patient?
A. Low urinary citrate concentration
B. High urinary magnesium concentration
C. High urinary pH above 7.0
D. Low urinary uric acid concentration
Answer: A
Rationale: Calcium oxalate stones form when urine is supersaturated with calcium and oxalate. Citrate is
a natural inhibitor of stone formation because it binds calcium and reduces supersaturation. Low
urinary citrate (hypocitraturia) is a common risk factor, especially in patients with metabolic acidosis
(e.g., from diabetes or hypertension). High magnesium would inhibit stone formation. High pH (>7.0)
favors calcium phosphate stones, not calcium oxalate. Low uric acid is not directly related to calcium
oxalate stones; hyperuricosuria can promote calcium oxalate stones via heterogeneous nucleation.
4. A 60-year-old patient with a 30-pack-year smoking history presents with hemoptysis and weight
loss. Chest CT shows a 3 cm mass in the right upper lobe. Biopsy reveals small cell lung carcinoma.
Genetic analysis shows a mutation in the RB1 gene and loss of heterozygosity on chromosome 3p.
Which of the following additional molecular alterations is most likely to be present in this tumor?
A. EGFR activating mutation
B. ALK gene rearrangement
C. MYC amplification
D. KRAS mutation
Answer: C
Rationale: Small cell lung carcinoma (SCLC) is strongly associated with RB1 loss and 3p deletion. MYC
amplification is a common event in SCLC, contributing to its aggressive growth. EGFR mutations and
ALK rearrangements are typical of non-small cell lung cancer (NSCLC), especially adenocarcinoma.
KRAS mutations are also more common in NSCLC, particularly in smokers, but not characteristic of
SCLC. Therefore, MYC amplification is the most likely additional alteration.
5. A researcher is investigating the role of the complement system in a mouse model of sepsis. Mice
deficient in C3 show improved survival compared to wild-type mice after cecal ligation and
puncture. However, when these C3-deficient mice are also deficient in factor B, survival returns to
wild-type levels. Which of the following best explains this observation?
A. C3 deficiency prevents formation of the membrane attack complex, but factor B deficiency restores it via the
lectin pathway
B. C3 deficiency leads to uncontrolled activation of the alternative pathway, which is prevented by factor B
deficiency
C. Factor B deficiency impairs opsonization, compensating for the loss of C3
D. C3 deficiency increases production of C5a, which is toxic; factor B deficiency reduces C5a
Answer: B
Page 2
,Rationale: C3 is a central component of all complement pathways. In C3 deficiency, the alternative pathway cannot be
properly regulated because C3 is needed for feedback amplification. This leads to uncontrolled activation of the alternative
pathway via the C3b-dependent convertase, consuming complement components and causing excessive inflammation. Factor
B is essential for the alternative pathway; its deficiency prevents this uncontrolled activation, restoring survival. The other
options are incorrect: MAC formation is not restored by factor B deficiency; opsonization is impaired in both; C5a levels are
not increased by C3 deficiency.
6. A 50-year-old patient with chronic kidney disease (stage 4) presents with bone pain and a
pathological fracture of the femur. Laboratory studies show: serum calcium 8.2 mg/dL, phosphate
5.5 mg/dL, intact PTH 250 pg/mL (elevated), 25-hydroxyvitamin D 20 ng/mL (low normal), and
1,25-dihydroxyvitamin D 15 pg/mL (low). Which of the following best describes the pathogenesis of
the bone disease in this patient?
A. Osteomalacia due to vitamin D deficiency from impaired renal hydroxylation
B. Osteitis fibrosa cystica due to secondary hyperparathyroidism
C. Adynamic bone disease due to oversuppression of PTH
D. Osteoporosis due to corticosteroid therapy
Answer: B
Rationale: In chronic kidney disease, hyperphosphatemia and low 1,25-dihydroxyvitamin D stimulate
PTH secretion (secondary hyperparathyroidism). Elevated PTH increases bone turnover, leading to
osteitis fibrosa cystica, characterized by bone pain, fractures, and subperiosteal resorption. The low
1,25-dihydroxyvitamin D is due to impaired 1-hydroxylase activity in the kidney. While vitamin D
deficiency contributes, the predominant lesion is high-turnover bone disease from hyperparathyroidism.
Adynamic bone disease is associated with low PTH, not elevated. Osteoporosis is not the primary
diagnosis.
7. A 35-year-old patient with a family history of breast cancer undergoes genetic testing and is
found to have a pathogenic variant in the BRCA1 gene. The patient asks about the increased risk
for other cancers. Which of the following cancers is this patient at highest risk for beyond breast
cancer?
A. Colorectal cancer
B. Pancreatic cancer
C. Ovarian cancer
D. Prostate cancer
Answer: C
Rationale: BRCA1 mutations confer a high risk of ovarian cancer (up to 40-60% lifetime risk). While
there is also increased risk for pancreatic and prostate cancers, the most significant and
well-established risk after breast cancer is ovarian cancer. Colorectal cancer is not strongly associated
with BRCA1 mutations. Therefore, ovarian cancer is the correct answer.
8. A patient with decompensated cirrhosis develops tense ascites. Paracentesis yields clear fluid
with a serum-ascites albumin gradient (SAAG) of 1.5 g/dL. The fluid total protein is 1.8 g/dL, and
the white blood cell count is 150 cells/L with 60% lymphocytes. Which of the following is the most
likely cause of the ascites?
Page 3
, A. Peritoneal carcinomatosis
B. Tuberculous peritonitis
C. Portal hypertension due to cirrhosis
D. Nephrotic syndrome
Answer: C
Rationale: A SAAG "e1.1 g/dL indicates portal hypertension as the cause of ascites. The low total protein
(<2.5 g/dL) is consistent with cirrhosis, where the hepatic sinusoids are capillarized, allowing
low-protein fluid to leak. Peritoneal carcinomatosis and tuberculous peritonitis typically cause exudative
ascites with SAAG <1.1 and high protein. Nephrotic syndrome can cause ascites but with SAAG <1.1
and high protein. The lymphocytic predominance is non-specific and can be seen in cirrhosis. Thus,
portal hypertension is the most likely.
9. A 55-year-old patient with a history of chronic hepatitis C develops jaundice and abdominal
pain. Laboratory results show: total bilirubin 8.5 mg/dL (direct 6.2), alkaline phosphatase 450 U/L
(elevated), AST 120 U/L, ALT 90 U/L. Ultrasound reveals dilated intrahepatic bile ducts. A CT
scan shows a mass at the hilum of the liver. Biopsy of the mass shows well-formed glands with
abundant desmoplastic stroma. Immunohistochemistry is positive for CK7 and negative for CK20.
Which of the following is the most likely diagnosis?
A. Hepatocellular carcinoma
B. Cholangiocarcinoma
C. Metastatic colorectal adenocarcinoma
D. Gallbladder carcinoma
Answer: B
Rationale: The clinical presentation of obstructive jaundice with dilated intrahepatic ducts and a hilar
mass is classic for perihilar cholangiocarcinoma (Klatskin tumor). Histology shows glands with
desmoplasia, and immunohistochemistry (CK7+/CK20-) is typical of cholangiocarcinoma.
Hepatocellular carcinoma would not cause bile duct obstruction and is usually CK7-/CK20-. Metastatic
colorectal cancer is CK7-/CK20+. Gallbladder carcinoma would present with a mass in the gallbladder
fossa, not hilar.
10. A 40-year-old patient with a history of recurrent deep vein thrombosis and pulmonary
embolism is found to have a prolonged activated partial thromboplastin time (aPTT) that does not
correct with mixing studies. Further testing shows elevated levels of anti-cardiolipin antibodies.
Which of the following mechanisms best explains the thrombotic tendency in this patient?
A. Antibody-mediated inhibition of protein C activation
B. Antibody-mediated activation of platelets
C. Antibody-mediated blockade of antithrombin III
D. Antibody-mediated increase in tissue factor expression
Answer: A
Rationale: Antiphospholipid syndrome (APS) is characterized by autoantibodies against
phospholipid-binding proteins. The lupus anticoagulant (a type of antiphospholipid antibody) prolongs
aPTT due to interference with phospholipid-dependent coagulation tests. The thrombotic tendency is
thought to be due to antibodies that inhibit the protein C pathway, reducing the inactivation of factor Va
and VIIIa. Other mechanisms include interference with annexin A5 and activation of endothelial cells.
Page 4
