ADVANCED PATHOPHYSIOLOGY NU606 EXAM GUIDE
2026/27 QUESTIONS AND VERIFIED SOLUTIONS
1. A 45-year-old male presents with fatigue, weight loss, and diffuse
hyperpigmentation. Laboratory findings show hyponatremia, hyperkalemia, and
hypoglycemia. ACTH levels are elevated. Which of the following is the most likely
mechanism of his hyperpigmentation?
A. Increased alpha-MSH binding to MC1 receptors
B. Direct stimulation of melanocytes by aldosterone
C. Increased cortisol feedback inhibition on the pituitary
D. Reduced degradation of beta-lipotropin in peripheral tissues
Correct Answer: A
*Explanation: Elevated ACTH in primary adrenal insufficiency is derived from pro-
opiomelanocortin (POMC), which also produces alpha-MSH. Alpha-MSH binds
MC1 receptors on melanocytes, causing hyperpigmentation. Aldosterone does
not affect melanocytes (B). Cortisol is low, not high (C). Beta-lipotropin
HEdegradation is not primarily involved (D).*
2. A patient with chronic alcoholism develops painful asymmetric muscle weakness
and dark urine after a binge. Serum creatine kinase is 15,000 U/L, and renal
function shows elevated BUN and creatinine. Which cellular mechanism best
explains the acute kidney injury in this condition?
A. Immune complex deposition in glomeruli
B. Myoglobin-induced tubular obstruction and oxidative injury
C. Direct alcohol toxicity to proximal tubule cells
D. Rhabdomyolysis-mediated hypovolemia from third spacing
Correct Answer: B
Explanation: Alcohol-induced rhabdomyolysis releases myoglobin, which
precipitates in renal tubules, causes obstruction, and generates free radicals,
leading to acute tubular injury. Immune complexes (A) are not typical. Direct
toxicity (C) is minor. Hypovolemia (D) may occur but is not the primary mechanism
of injury.
,3. A newborn presents with persistent hypoglycemia, hepatomegaly, and seizures.
Laboratory analysis reveals fasting hypoglycemia, lactic acidosis,
hypertriglyceridemia, and hyperuricemia. A liver biopsy shows abundant glycogen
with normal structure. Which enzyme deficiency is most likely?
A. Glucose-6-phosphatase
B. Liver phosphorylase
C. Glycogen debranching enzyme
D. Muscle phosphorylase
Correct Answer: A
*Explanation: Glucose-6-phosphatase deficiency (von Gierke disease) causes
inability to produce free glucose from glucose-6-phosphate, leading to fasting
hypoglycemia, lactic acidosis (from glycolysis), hypertriglyceridemia, and
hyperuricemia. Biopsy shows normal glycogen structure. Liver phosphorylase (B)
causes milder symptoms. Debranching enzyme (C) (Cori disease) shows abnormal
glycogen structure. Muscle phosphorylase (D) (McArdle) causes exercise
intolerance, not fasting hypoglycemia.*
4. A 68-year-old woman presents with acute-onset shortness of breath, right leg
swelling, and pleuritic chest pain. She has a history of atrial fibrillation but is not
anticoagulated. Which physiological change most directly predisposed her to this
condition?
A. Decreased atrial natriuretic peptide secretion
B. Left atrial enlargement with loss of effective contraction
C. Elevated pulmonary capillary wedge pressure
D. Increased systemic vascular resistance
Correct Answer: B
Explanation: Atrial fibrillation leads to loss of effective atrial contraction and stasis
in the left atrium (or appendage), promoting thrombus formation. Embolization to
pulmonary arteries occurs if the thrombus is from right heart (less common) or
paradoxical embolus, but in AF, left atrial thrombus embolizes systemically. The
question indicates leg swelling → DVT likely, then PE. However, AF-related stasis is
the key predisposition in this clinical picture.
,5. A researcher studying sepsis administers lipopolysaccharide to mice and
measures cytokines. Which cytokine is most responsible for inducing the acute
phase response, including fever and increased hepatic synthesis of C-reactive
protein?
A. Interleukin-2
B. Interleukin-6
C. Interferon-gamma
D. Tumor necrosis factor-alpha
Correct Answer: B
*Explanation: IL-6 is the primary mediator of the acute phase response, acting on
hepatocytes to produce CRP, fibrinogen, and serum amyloid A, and on
hypothalamus to induce fever. IL-2 (A) drives T-cell proliferation. IFN-gamma (C)
activates macrophages. TNF-alpha (D) causes shock and endothelial activation
but is less direct for hepatic acute phase proteins.*
6. A 32-year-old woman with systemic lupus erythematosus develops nephrotic
syndrome. Renal biopsy shows diffuse thickening of glomerular basement
membrane with "wire-loop" lesions on light microscopy and subendothelial
electron-dense deposits on electron microscopy. Which immune mechanism is
primarily responsible?
A. Type I hypersensitivity with mast cell degranulation
B. Type II cytotoxic antibody against podocyte antigens
C. Type III immune complex deposition
D. Type IV T-cell mediated granulomatous reaction
Correct Answer: C
Explanation: Lupus nephritis class V (membranous) or mixed patterns involve
deposition of circulating immune complexes (Type III hypersensitivity) in
subendothelial and mesangial regions, activating complement. Type I (A) causes
allergy. Type II (B) occurs in Goodpasture or autoimmune hemolytic anemia. Type
IV (D) occurs in TB or contact dermatitis.
7. A premature infant receives high concentrations of supplemental oxygen for
respiratory distress syndrome. At 3 weeks of age, the infant develops increasing
oxygen requirements and diffuse bilateral alveolar infiltrates. Which of the
, following pathological changes is most likely present in the lungs?
A. Hyaline membrane formation
B. Alveolar type II cell hyperplasia with interstitial fibrosis
C. Pulmonary artery smooth muscle hypertrophy
D. Intra-alveolar accumulation of proteinaceous fluid
Correct Answer: B
Explanation: Bronchopulmonary dysplasia (chronic lung disease of prematurity)
results from oxygen toxicity and barotrauma, causing alveolar type II cell
hyperplasia, interstitial fibrosis, and airway remodeling. Hyaline membranes (A) are
acute RDS finding. Pulmonary artery hypertrophy (C) occurs in pulmonary
hypertension. Proteinaceous fluid (D) suggests pulmonary edema.
8. A 55-year-old male with type 2 diabetes and hypertension presents with
progressive dyspnea on exertion. Echocardiography reveals concentric left
ventricular hypertrophy with a normal cavity size and preserved ejection fraction.
Which cellular adaptation best explains this finding?
A. Hyperplasia of cardiomyocytes
B. Sarcomere loss with mitochondrial accumulation
C. Increased myocyte size due to parallel sarcomere addition
D. Replacement fibrosis with adipocyte infiltration
Correct Answer: C
Explanation: Pressure overload (hypertension, aortic stenosis) causes concentric
hypertrophy via parallel addition of sarcomeres, increasing myocyte width and wall
thickness. Hyperplasia (A) does not occur in adult myocytes. Sarcomere loss (B)
occurs in dilated cardiomyopathy. Replacement fibrosis (D) occurs after infarction.
9. A 22-year-old man presents with sudden-onset shortness of breath and sharp
chest pain after a transatlantic flight. He is tachycardic and hypoxic. CT
angiography shows bilateral pulmonary emboli. Which underlying condition is
most likely to predispose to this presentation at his age?
A. Antithrombin III deficiency
B. Sickle cell trait
C. Paroxysmal nocturnal hemoglobinuria
D. Hyperhomocysteinemia due to MTHFR mutation
2026/27 QUESTIONS AND VERIFIED SOLUTIONS
1. A 45-year-old male presents with fatigue, weight loss, and diffuse
hyperpigmentation. Laboratory findings show hyponatremia, hyperkalemia, and
hypoglycemia. ACTH levels are elevated. Which of the following is the most likely
mechanism of his hyperpigmentation?
A. Increased alpha-MSH binding to MC1 receptors
B. Direct stimulation of melanocytes by aldosterone
C. Increased cortisol feedback inhibition on the pituitary
D. Reduced degradation of beta-lipotropin in peripheral tissues
Correct Answer: A
*Explanation: Elevated ACTH in primary adrenal insufficiency is derived from pro-
opiomelanocortin (POMC), which also produces alpha-MSH. Alpha-MSH binds
MC1 receptors on melanocytes, causing hyperpigmentation. Aldosterone does
not affect melanocytes (B). Cortisol is low, not high (C). Beta-lipotropin
HEdegradation is not primarily involved (D).*
2. A patient with chronic alcoholism develops painful asymmetric muscle weakness
and dark urine after a binge. Serum creatine kinase is 15,000 U/L, and renal
function shows elevated BUN and creatinine. Which cellular mechanism best
explains the acute kidney injury in this condition?
A. Immune complex deposition in glomeruli
B. Myoglobin-induced tubular obstruction and oxidative injury
C. Direct alcohol toxicity to proximal tubule cells
D. Rhabdomyolysis-mediated hypovolemia from third spacing
Correct Answer: B
Explanation: Alcohol-induced rhabdomyolysis releases myoglobin, which
precipitates in renal tubules, causes obstruction, and generates free radicals,
leading to acute tubular injury. Immune complexes (A) are not typical. Direct
toxicity (C) is minor. Hypovolemia (D) may occur but is not the primary mechanism
of injury.
,3. A newborn presents with persistent hypoglycemia, hepatomegaly, and seizures.
Laboratory analysis reveals fasting hypoglycemia, lactic acidosis,
hypertriglyceridemia, and hyperuricemia. A liver biopsy shows abundant glycogen
with normal structure. Which enzyme deficiency is most likely?
A. Glucose-6-phosphatase
B. Liver phosphorylase
C. Glycogen debranching enzyme
D. Muscle phosphorylase
Correct Answer: A
*Explanation: Glucose-6-phosphatase deficiency (von Gierke disease) causes
inability to produce free glucose from glucose-6-phosphate, leading to fasting
hypoglycemia, lactic acidosis (from glycolysis), hypertriglyceridemia, and
hyperuricemia. Biopsy shows normal glycogen structure. Liver phosphorylase (B)
causes milder symptoms. Debranching enzyme (C) (Cori disease) shows abnormal
glycogen structure. Muscle phosphorylase (D) (McArdle) causes exercise
intolerance, not fasting hypoglycemia.*
4. A 68-year-old woman presents with acute-onset shortness of breath, right leg
swelling, and pleuritic chest pain. She has a history of atrial fibrillation but is not
anticoagulated. Which physiological change most directly predisposed her to this
condition?
A. Decreased atrial natriuretic peptide secretion
B. Left atrial enlargement with loss of effective contraction
C. Elevated pulmonary capillary wedge pressure
D. Increased systemic vascular resistance
Correct Answer: B
Explanation: Atrial fibrillation leads to loss of effective atrial contraction and stasis
in the left atrium (or appendage), promoting thrombus formation. Embolization to
pulmonary arteries occurs if the thrombus is from right heart (less common) or
paradoxical embolus, but in AF, left atrial thrombus embolizes systemically. The
question indicates leg swelling → DVT likely, then PE. However, AF-related stasis is
the key predisposition in this clinical picture.
,5. A researcher studying sepsis administers lipopolysaccharide to mice and
measures cytokines. Which cytokine is most responsible for inducing the acute
phase response, including fever and increased hepatic synthesis of C-reactive
protein?
A. Interleukin-2
B. Interleukin-6
C. Interferon-gamma
D. Tumor necrosis factor-alpha
Correct Answer: B
*Explanation: IL-6 is the primary mediator of the acute phase response, acting on
hepatocytes to produce CRP, fibrinogen, and serum amyloid A, and on
hypothalamus to induce fever. IL-2 (A) drives T-cell proliferation. IFN-gamma (C)
activates macrophages. TNF-alpha (D) causes shock and endothelial activation
but is less direct for hepatic acute phase proteins.*
6. A 32-year-old woman with systemic lupus erythematosus develops nephrotic
syndrome. Renal biopsy shows diffuse thickening of glomerular basement
membrane with "wire-loop" lesions on light microscopy and subendothelial
electron-dense deposits on electron microscopy. Which immune mechanism is
primarily responsible?
A. Type I hypersensitivity with mast cell degranulation
B. Type II cytotoxic antibody against podocyte antigens
C. Type III immune complex deposition
D. Type IV T-cell mediated granulomatous reaction
Correct Answer: C
Explanation: Lupus nephritis class V (membranous) or mixed patterns involve
deposition of circulating immune complexes (Type III hypersensitivity) in
subendothelial and mesangial regions, activating complement. Type I (A) causes
allergy. Type II (B) occurs in Goodpasture or autoimmune hemolytic anemia. Type
IV (D) occurs in TB or contact dermatitis.
7. A premature infant receives high concentrations of supplemental oxygen for
respiratory distress syndrome. At 3 weeks of age, the infant develops increasing
oxygen requirements and diffuse bilateral alveolar infiltrates. Which of the
, following pathological changes is most likely present in the lungs?
A. Hyaline membrane formation
B. Alveolar type II cell hyperplasia with interstitial fibrosis
C. Pulmonary artery smooth muscle hypertrophy
D. Intra-alveolar accumulation of proteinaceous fluid
Correct Answer: B
Explanation: Bronchopulmonary dysplasia (chronic lung disease of prematurity)
results from oxygen toxicity and barotrauma, causing alveolar type II cell
hyperplasia, interstitial fibrosis, and airway remodeling. Hyaline membranes (A) are
acute RDS finding. Pulmonary artery hypertrophy (C) occurs in pulmonary
hypertension. Proteinaceous fluid (D) suggests pulmonary edema.
8. A 55-year-old male with type 2 diabetes and hypertension presents with
progressive dyspnea on exertion. Echocardiography reveals concentric left
ventricular hypertrophy with a normal cavity size and preserved ejection fraction.
Which cellular adaptation best explains this finding?
A. Hyperplasia of cardiomyocytes
B. Sarcomere loss with mitochondrial accumulation
C. Increased myocyte size due to parallel sarcomere addition
D. Replacement fibrosis with adipocyte infiltration
Correct Answer: C
Explanation: Pressure overload (hypertension, aortic stenosis) causes concentric
hypertrophy via parallel addition of sarcomeres, increasing myocyte width and wall
thickness. Hyperplasia (A) does not occur in adult myocytes. Sarcomere loss (B)
occurs in dilated cardiomyopathy. Replacement fibrosis (D) occurs after infarction.
9. A 22-year-old man presents with sudden-onset shortness of breath and sharp
chest pain after a transatlantic flight. He is tachycardic and hypoxic. CT
angiography shows bilateral pulmonary emboli. Which underlying condition is
most likely to predispose to this presentation at his age?
A. Antithrombin III deficiency
B. Sickle cell trait
C. Paroxysmal nocturnal hemoglobinuria
D. Hyperhomocysteinemia due to MTHFR mutation
