N582 Midterm Actual Exam Foundations &
Systems 1-4 Complete Practice Test with
Verified Solutions
DOMAIN 1: CELLULAR & GENETIC FOUNDATIONS
Q1. A 68-year-old man with chronic hypertension presents with fatigue and edema. BP
158/96, serum Na⁺ 128 mEq/L (normal 135-145), urine osmolality 550 mOsm/kg
(normal 50-1200). He takes hydrochlorothiazide 25mg daily. The most likely
pathophysiological mechanism for his hyponatremia is:
A. Syndrome of Inappropriate ADH (SIADH) from lung cancer
B. Diuretic-induced volume depletion with appropriate ADH response
C. Psychogenic polydipsia from psychiatric medications
D. Addison's disease with mineralocorticoid deficiency
Correct Answer: B
Rationale: Thiazide diuretics block the Na⁺-Cl⁻ cotransporter in the distal convoluted
tubule, causing sodium loss and volume depletion. The hypertonic urine (550
mOsm/kg) indicates appropriate ADH secretion in response to volume depletion,
differentiating this from SIADH which would present with euvolemia and inappropriately
concentrated urine despite hyponatremia. Psychogenic polydipsia produces dilute urine
,(<100 mOsm/kg). Addison's disease causes hyperkalemia and hypotension, not just
hyponatremia.
Q2. A 45-year-old woman develops numbness and tingling in her fingers. Labs reveal
Hgb 9.2 g/dL, MCV 108 fL, vitamin B12 180 pg/mL (normal >300), homocysteine 22
µmol/L (normal <15), methylmalonic acid 0.8 µmol/L (normal <0.4). The
pathophysiological mechanism explaining her macrocytic anemia is:
A. Folate deficiency from inadequate dietary intake
B. Vitamin B12 deficiency impairing DNA synthesis
C. Alcohol-induced bone marrow suppression
D. Liver disease causing cholesterol membrane abnormalities
Correct Answer: B
Rationale: Elevated methylmalonic acid (MMA) and homocysteine with low B12
confirms B12 deficiency. B12 is required as a cofactor for methionine synthase
(homocysteine metabolism) and methylmalonyl-CoA mutase. Deficiency impairs DNA
synthesis, causing megaloblastic anemia with macrocytosis and neurological
symptoms. Folate deficiency elevates homocysteine but NOT methylmalonic acid.
Alcohol and liver disease do not typically cause this specific metabolic pattern.
Q3. A patient presents with severe metabolic acidosis (pH 7.15, HCO₃⁻ 12, pCO₂ 28),
anion gap 28 (normal 8-16), and lactate 6.5 mmol/L. The most likely pathophysiological
mechanism is:
A. Renal tubular acidosis type 1
,B. Lactic acidosis from tissue hypoperfusion
C. Diabetic ketoacidosis
D. Salicylate intoxication
Correct Answer: B
Rationale: High anion gap metabolic acidosis (HAGMA) with elevated lactate indicates
lactic acidosis. The anion gap formula (Na⁺ - [Cl⁻ + HCO₃⁻]) reveals unmeasured anions;
lactate accumulation from anaerobic metabolism (shock, hypoxia) is the most common
cause. RTA type 1 causes normal anion gap acidosis. DKA would show ketonemia and
glucose >250 mg/dL. Salicylate intoxication causes mixed respiratory alkalosis and
metabolic acidosis with respiratory rate increase.
Q4. A 28-year-old woman develops joint pain, malar rash, and photosensitivity. ANA is
positive 1:640, anti-dsDNA positive, C3 low. The underlying immunological mechanism
is:
A. Type I hypersensitivity (IgE-mediated)
B. Type II hypersensitivity (antibody-mediated cytotoxicity)
C. Type III hypersensitivity (immune complex deposition)
D. Type IV hypersensitivity (T-cell mediated)
Correct Answer: C
Rationale: Systemic lupus erythematosus (SLE) is a classic Type III hypersensitivity
reaction. Autoantibodies (anti-dsDNA) form immune complexes that deposit in tissues
(kidneys, skin, joints), activate complement (low C3), and cause inflammation. Type I is
, immediate allergy (anaphylaxis). Type II involves antibodies against cell surfaces
(autoimmune hemolytic anemia). Type IV is delayed-type (contact dermatitis, TB skin
test).
Q5. A patient with chronic hepatitis C develops hepatocellular carcinoma. The cellular
adaptation that preceded malignant transformation was most likely:
A. Metaplasia of hepatocytes to squamous epithelium
B. Dysplasia with cellular atypia and disordered architecture
C. Hypertrophy from increased metabolic demand
D. Hyperplasia with normal-appearing hepatocyte proliferation
Correct Answer: B
Rationale: Dysplasia (disordered cellular growth with nuclear atypia, pleomorphism, and
loss of polarity) is the premalignant cellular adaptation. In chronic liver disease,
dysplastic nodules progress to hepatocellular carcinoma. Metaplasia is reversible
change of one differentiated cell type to another (not typical in liver). Hypertrophy is
increased cell size. Hyperplasia is increased cell number with normal morphology.
DOMAIN 2: CARDIOVASCULAR & HEMATOLOGIC SYSTEMS
Q6. A 72-year-old woman with heart failure (EF 35%) presents with worsening dyspnea.
Current medications: lisinopril 10mg daily, metoprolol succinate 25mg daily, furosemide
40mg daily. Exam: JVD 8cm, bilateral crackles, S3 gallop, lower extremity edema. BP
112/68, HR 72. The most appropriate pharmacological adjustment is:
A. Increase lisinopril to 20mg daily
Systems 1-4 Complete Practice Test with
Verified Solutions
DOMAIN 1: CELLULAR & GENETIC FOUNDATIONS
Q1. A 68-year-old man with chronic hypertension presents with fatigue and edema. BP
158/96, serum Na⁺ 128 mEq/L (normal 135-145), urine osmolality 550 mOsm/kg
(normal 50-1200). He takes hydrochlorothiazide 25mg daily. The most likely
pathophysiological mechanism for his hyponatremia is:
A. Syndrome of Inappropriate ADH (SIADH) from lung cancer
B. Diuretic-induced volume depletion with appropriate ADH response
C. Psychogenic polydipsia from psychiatric medications
D. Addison's disease with mineralocorticoid deficiency
Correct Answer: B
Rationale: Thiazide diuretics block the Na⁺-Cl⁻ cotransporter in the distal convoluted
tubule, causing sodium loss and volume depletion. The hypertonic urine (550
mOsm/kg) indicates appropriate ADH secretion in response to volume depletion,
differentiating this from SIADH which would present with euvolemia and inappropriately
concentrated urine despite hyponatremia. Psychogenic polydipsia produces dilute urine
,(<100 mOsm/kg). Addison's disease causes hyperkalemia and hypotension, not just
hyponatremia.
Q2. A 45-year-old woman develops numbness and tingling in her fingers. Labs reveal
Hgb 9.2 g/dL, MCV 108 fL, vitamin B12 180 pg/mL (normal >300), homocysteine 22
µmol/L (normal <15), methylmalonic acid 0.8 µmol/L (normal <0.4). The
pathophysiological mechanism explaining her macrocytic anemia is:
A. Folate deficiency from inadequate dietary intake
B. Vitamin B12 deficiency impairing DNA synthesis
C. Alcohol-induced bone marrow suppression
D. Liver disease causing cholesterol membrane abnormalities
Correct Answer: B
Rationale: Elevated methylmalonic acid (MMA) and homocysteine with low B12
confirms B12 deficiency. B12 is required as a cofactor for methionine synthase
(homocysteine metabolism) and methylmalonyl-CoA mutase. Deficiency impairs DNA
synthesis, causing megaloblastic anemia with macrocytosis and neurological
symptoms. Folate deficiency elevates homocysteine but NOT methylmalonic acid.
Alcohol and liver disease do not typically cause this specific metabolic pattern.
Q3. A patient presents with severe metabolic acidosis (pH 7.15, HCO₃⁻ 12, pCO₂ 28),
anion gap 28 (normal 8-16), and lactate 6.5 mmol/L. The most likely pathophysiological
mechanism is:
A. Renal tubular acidosis type 1
,B. Lactic acidosis from tissue hypoperfusion
C. Diabetic ketoacidosis
D. Salicylate intoxication
Correct Answer: B
Rationale: High anion gap metabolic acidosis (HAGMA) with elevated lactate indicates
lactic acidosis. The anion gap formula (Na⁺ - [Cl⁻ + HCO₃⁻]) reveals unmeasured anions;
lactate accumulation from anaerobic metabolism (shock, hypoxia) is the most common
cause. RTA type 1 causes normal anion gap acidosis. DKA would show ketonemia and
glucose >250 mg/dL. Salicylate intoxication causes mixed respiratory alkalosis and
metabolic acidosis with respiratory rate increase.
Q4. A 28-year-old woman develops joint pain, malar rash, and photosensitivity. ANA is
positive 1:640, anti-dsDNA positive, C3 low. The underlying immunological mechanism
is:
A. Type I hypersensitivity (IgE-mediated)
B. Type II hypersensitivity (antibody-mediated cytotoxicity)
C. Type III hypersensitivity (immune complex deposition)
D. Type IV hypersensitivity (T-cell mediated)
Correct Answer: C
Rationale: Systemic lupus erythematosus (SLE) is a classic Type III hypersensitivity
reaction. Autoantibodies (anti-dsDNA) form immune complexes that deposit in tissues
(kidneys, skin, joints), activate complement (low C3), and cause inflammation. Type I is
, immediate allergy (anaphylaxis). Type II involves antibodies against cell surfaces
(autoimmune hemolytic anemia). Type IV is delayed-type (contact dermatitis, TB skin
test).
Q5. A patient with chronic hepatitis C develops hepatocellular carcinoma. The cellular
adaptation that preceded malignant transformation was most likely:
A. Metaplasia of hepatocytes to squamous epithelium
B. Dysplasia with cellular atypia and disordered architecture
C. Hypertrophy from increased metabolic demand
D. Hyperplasia with normal-appearing hepatocyte proliferation
Correct Answer: B
Rationale: Dysplasia (disordered cellular growth with nuclear atypia, pleomorphism, and
loss of polarity) is the premalignant cellular adaptation. In chronic liver disease,
dysplastic nodules progress to hepatocellular carcinoma. Metaplasia is reversible
change of one differentiated cell type to another (not typical in liver). Hypertrophy is
increased cell size. Hyperplasia is increased cell number with normal morphology.
DOMAIN 2: CARDIOVASCULAR & HEMATOLOGIC SYSTEMS
Q6. A 72-year-old woman with heart failure (EF 35%) presents with worsening dyspnea.
Current medications: lisinopril 10mg daily, metoprolol succinate 25mg daily, furosemide
40mg daily. Exam: JVD 8cm, bilateral crackles, S3 gallop, lower extremity edema. BP
112/68, HR 72. The most appropriate pharmacological adjustment is:
A. Increase lisinopril to 20mg daily
