NR-507 – Advanced Pathophysiology Advanced study of disease mechanisms, physiological dysfunctions, diagnostic implications, clinical manifestations, and healthcare management.

NR-507 – Advanced Pathophysiology Advanced
study of disease mechanisms, physiological
dysfunctions, diagnostic implications, clinical
manifestations, and healthcare management.


Question 1
A 45-year-old male with a history of alcohol use disorder presents with jaundice,
ascites, and asterixis. Laboratory results show AST:ALT ratio >2, elevated
bilirubin, and low albumin. The most likely underlying mechanism of liver injury
is:
A) Autoimmune destruction of hepatocytes
B) Accumulation of fat leading to steatohepatitis
C) Mitochondrial injury from acetaldehyde and oxidative stress
D) Viral-induced immune complex deposition
Answer: C – Rationale: Alcoholic liver disease results from ethanol metabolism
→ acetaldehyde → mitochondrial damage, oxidative stress, inflammation, and
fibrosis. AST:ALT >2 is characteristic.


Question 2
A patient with chronic kidney disease stage 4 has serum phosphate of 7.2 mg/dL
and calcium of 7.0 mg/dL. The expected compensatory mechanism is:
A) Decreased parathyroid hormone (PTH)
B) Increased PTH (secondary hyperparathyroidism)
C) Increased calcitonin
D) Decreased vitamin D synthesis (already low) – but the key is increased PTH
Answer: B – Rationale: Hyperphosphatemia and hypocalcemia in CKD stimulate
PTH secretion (secondary hyperparathyroidism) to maintain calcium, but PTH
cannot excrete phosphate due to low GFR.

,Question 3
A patient with systemic lupus erythematosus (SLE) develops diffuse proliferative
glomerulonephritis. Which immune complex deposition pattern is most likely?
A) Linear IgG along glomerular basement membrane (Goodpasture)
B) Granular immune complexes in subendothelial and mesangial areas
C) Pauci-immune (no immune complexes)
D) IgA-dominant mesangial deposits
Answer: B – Rationale: SLE nephritis (Class IV) shows subendothelial and
mesangial granular immune complexes (IgG, IgM, IgA, C3) on
immunofluorescence.


Question 4
A patient with small cell lung cancer develops hyponatremia (serum Na 118
mEq/L) with urine osmolality 500 mOsm/kg (concentrated). The most likely
paraneoplastic syndrome is:
A) Syndrome of inappropriate antidiuretic hormone (SIADH)
B) Cerebral salt wasting
C) Addison’s disease
D) Diabetes insipidus
Answer: A – Rationale: Small cell lung cancer produces ectopic ADH → SIADH
→ hyponatremia with concentrated urine and euvolemia.


Question 5
A 60-year-old with hypertension and diabetes presents with sudden onset of
painless hematuria. CT scan reveals a renal mass. Which genetic abnormality is
most associated with clear cell renal cell carcinoma?
A) BRAF mutation
B) VHL gene inactivation on chromosome 3p
C) EGFR amplification
D) HER2/neu overexpression
Answer: B – Rationale: Clear cell RCC is associated with VHL tumor suppressor
gene inactivation (3p25), leading to HIF accumulation and angiogenesis.

,Question 6
A patient with a large anterior wall myocardial infarction develops a new systolic
murmur at the apex 3 days later. The most likely diagnosis is:
A) Ventricular septal rupture
B) Papillary muscle rupture (mitral regurgitation)
C) Acute pericarditis
D) Aortic stenosis
Answer: B – Rationale: Post-MI, papillary muscle rupture (usually
posteromedial) causes acute severe MR with apical holosystolic murmur and
shock. VSD presents with harsh holosystolic murmur at left sternal border.


Question 7
A newborn presents with respiratory distress, cyanosis, and decreased breath
sounds on the left. Chest X-ray shows a hyperlucent left lung with mediastinal shift
to the right. The most likely diagnosis is:
A) Congenital diaphragmatic hernia
B) Congenital lobar emphysema (left upper lobe)
C) Pulmonary sequestration
D) Respiratory distress syndrome
Answer: B – Rationale: Congenital lobar emphysema (CLE) causes overinflation
of a lobe (often left upper) → hyperlucency, mediastinal shift, respiratory distress.
Surgical lobectomy may be needed.


Question 8
A patient with ulcerative colitis for 12 years develops bloody diarrhea, weight loss,
and a new stricture on colonoscopy. Biopsy shows dysplasia. The most concerning
complication is:
A) Toxic megacolon
B) Colorectal cancer
C) Primary sclerosing cholangitis
D) Perforation

, Answer: B – *Rationale: Long-standing ulcerative colitis (≥8-10 years) increases
colorectal cancer risk. Dysplasia is a precursor. Regular surveillance colonoscopy
is recommended.*


Question 9
A patient with septic shock has a serum lactate of 8 mmol/L. The primary
mechanism of hyperlactatemia in sepsis is:
A) Increased hepatic clearance
B) Type A (hypoxic) and type B (impaired utilization) – but best answer: tissue
hypoxia from hypoperfusion and microvascular dysfunction
C) Increased gluconeogenesis
D) Alkalosis
Answer: B – Rationale: Septic shock causes hypoperfusion (Type A lactate) and
mitochondrial dysfunction with impaired pyruvate utilization (Type B).


Question 10
A patient with chronic myelogenous leukemia (CML) has the Philadelphia
chromosome. This translocation involves:
A) t(9;22) → BCR-ABL fusion with constitutive tyrosine kinase activity
B) t(15;17) → PML-RARA
C) t(8;14) → MYC activation
D) t(11;14) → cyclin D1
Answer: A – *Rationale: CML is caused by t(9;22)(q34;q11) → BCR-ABL fusion
gene → unregulated tyrosine kinase → myeloid proliferation.*


Question 11
A 25-year-old female with Graves’ disease develops pretibial myxedema and
ophthalmopathy. These findings are caused by:
A) Direct thyroid hormone toxicity
B) Autoantibodies against TSH receptor cross-reacting with orbital and dermal
fibroblasts