Internal Medicine Step 2 CK: 8 High-Yield Practice Questions
USMLE Step 2 CK internal medicine covers clinical decision-making across all medicine subspecialties. These 8 questions target the highest-yield Step 2 clinical management scenarios — the ones that appear most frequently on the exam.
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update Updated October 2026
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Question 1 of 8Score: 0 / 0
Q1Diabetes Management
A 55-year-old with type 2 diabetes and CKD stage 3a (GFR 48) has HbA1c 8.9%. His current medication is metformin 1000mg twice daily. What is the next best step?
Explanation: An SGLT2 inhibitor (empagliflozin or dapagliflozin) is the preferred add-on for type 2 diabetes with CKD — guidelines recommend SGLT2i in T2DM patients with CKD (eGFR ≥20) to slow CKD progression (renal protective effect independent of glycemic control). Canagliflozin and dapagliflozin specifically have FDA approval for CKD progression reduction. Sulfonylureas risk hypoglycemia and do not offer cardiorenal protection. Metformin is safe at GFR ≥30 (can continue). Insulin would be appropriate for HbA1c >10 or symptomatic hyperglycemia.
Q2Hepatology
A 62-year-old with cirrhosis presents with confusion, asterixis, and bilateral symmetric tremor. Ammonia is 98 μmol/L (normal <35). What is the first-line treatment?
Explanation: Hepatic encephalopathy: first-line treatment is lactulose, titrated to produce 2-3 soft bowel movements per day. Lactulose acidifies the colon → converts NH3 (ammonia) to NH4+ (ammonium, not absorbed) + acts as cathartic. Rifaximin is added as secondary prophylaxis after first episode to prevent recurrence. Protein restriction is outdated — patients should maintain adequate protein intake (1.0-1.5g/kg/day) because malnutrition worsens outcomes. Identify and treat precipitants: GI bleed (#1 precipitant), infection, constipation, sedatives, electrolyte disturbances.
Q3Thyroid Disorders
A 48-year-old woman has fatigue, constipation, weight gain, and cold intolerance. TSH is 12.4 mIU/L (normal 0.4-4.0), free T4 is 0.6 ng/dL (low). What is the most appropriate next step?
Explanation: Overt hypothyroidism (elevated TSH + low free T4 + symptoms): start levothyroxine immediately. Initial dose: 1.6 mcg/kg/day in young healthy adults; start lower (25-50 mcg/day) in elderly or those with cardiac disease. Recheck TSH in 6-8 weeks and titrate. Use synthetic T4 (levothyroxine) monotherapy — T3 (liothyronine) not recommended for routine hypothyroidism (short half-life, symptom fluctuation). Thyroid biopsy is for nodules. Subclinical hypothyroidism (elevated TSH + normal T4) with TSH >10 or symptoms: treat with levothyroxine.
Q4Glomerulonephritis and Nephrotic Syndrome
A 35-year-old woman with SLE has new-onset nephrotic syndrome. Urinalysis shows 4+ protein. Anti-dsDNA antibody titer rises sharply. Complement levels (C3, C4) are low. The most likely diagnosis is:
Explanation: Active lupus nephritis: rising anti-dsDNA titers + falling complement (C3, C4) + nephrotic/nephritic syndrome = lupus nephritis until proven otherwise. Class III (focal proliferative) and Class IV (diffuse proliferative — most common and severe) present with hematuria + proteinuria + elevated creatinine + low complement. Diagnosis requires kidney biopsy for classification. Treatment: Class III/IV: induction with mycophenolate mofetil + high-dose glucocorticoids (or cyclophosphamide for severe disease); maintenance with MMF + hydroxychloroquine. Membranous nephropathy (LN class V) presents with pure nephrotic syndrome without hematuria.
Q5Hematologic Malignancy
A 70-year-old man is found to have monoclonal protein spike (M-spike 1.8 g/dL) on SPEP. Bone marrow biopsy shows 12% plasma cells. He has no symptoms, normal kidney function, calcium, and no bone lesions. The diagnosis is:
Explanation: Smoldering multiple myeloma (SMM): M-spike ≥3 g/dL OR bone marrow plasma cells 10-60% BUT no CRAB criteria (hyperCalcemia, Renal failure, Anemia, Bone lesions). This patient has 12% plasma cells and M-spike 1.8 g/dL — meets SMM criteria. MGUS: M-spike <3 g/dL AND <10% plasma cells AND no CRAB. Active myeloma: CRAB features or SLiM criteria (60% plasma cells, FLC ratio ≥100, >1 focal MRI lesion). Management of SMM: watchful waiting (daratumumab now being studied for high-risk SMM).
Q6Rheumatology
A patient with rheumatoid arthritis on methotrexate presents with cough, fever, and bilateral interstitial infiltrates on CXR. PFTs show a restrictive pattern. The most likely complication is:
Explanation: Methotrexate pneumonitis: hypersensitivity reaction (not dose-dependent) occurring at any time during therapy. Presents with dry cough, fever, dyspnea, bilateral interstitial infiltrates, restrictive PFTs. BAL shows eosinophilia. Management: STOP methotrexate immediately + systemic corticosteroids. Methotrexate pneumonitis is different from RA-associated ILD (fibrosing alveolitis) — the latter is slowly progressive and associated with high-titer RF. Always consider infection (PCP, atypical) before attributing to drug; can do BAL/bronchoscopy to rule out infection.
Q7Pulmonology
A 58-year-old with COPD and FEV1 35% (predicted) is hospitalized for COPD exacerbation. He is started on nebulized ipratropium + albuterol and systemic corticosteroids. On day 2, his PaCO2 is 72 mmHg and pH 7.28. The most appropriate respiratory support is:
Explanation: Acute hypercapnic respiratory failure in COPD exacerbation (pH <7.35, elevated PaCO2): BiPAP (noninvasive positive-pressure ventilation) is the preferred initial respiratory support. BiPAP reduces work of breathing, improves alveolar ventilation, and in COPD exacerbation reduces mortality and intubation rates compared to standard therapy. Indications: pH 7.25-7.35, RR >25, accessory muscle use, acute-on-chronic hypercapnia. High-flow NC does not support ventilation (no pressure support). High FiO2 in COPD can worsen hypercapnia (Haldane effect). Intubate if BiPAP fails, patient deteriorates, or cannot protect airway.
Q8Heart Failure
A 44-year-old with hypertension and obesity develops worsening leg edema, dyspnea on exertion, and orthopnea. Echo shows EF 58%, grade 3 diastolic dysfunction with elevated filling pressures. BNP is 420 pg/mL. The diagnosis is:
Explanation: HFpEF (EF ≥50% with diastolic dysfunction + elevated filling pressures + elevated BNP + symptoms): treatment focuses on diuretics for symptom relief (loop diuretics for fluid overload) + SGLT2 inhibitors (dapagliflozin/empagliflozin — now shown to reduce hospitalization and cardiovascular death in HFpEF). The 'four pillar' GDMT (ACEi/ARNI + beta-blocker + MRA + SGLT2i) is proven for HFrEF; for HFpEF, only SGLT2i has robust mortality data. Manage risk factors: BP control is critical (targets <130/80 in HFpEF).
What are the CRAB criteria for diagnosing active multiple myeloma?
CRAB criteria define organ damage from myeloma: C = hyperCalcemia (>10.5 mg/dL); R = Renal failure (creatinine >2 mg/dL from myeloma); A = Anemia (hemoglobin <10 g/dL from myeloma); B = Bone lesions (osteolytic lesions on skeletal survey or CT). Any one CRAB feature in a patient with ≥10% plasma cells confirms active myeloma requiring treatment. SLiM criteria (newer additions): 60% plasma cells, serum free light chain ratio ≥100, >1 focal lesion on MRI — these also indicate high-risk smoldering myeloma that requires treatment.
What is the first-line treatment for COPD exacerbation requiring hospitalization?
Hospitalized COPD exacerbation treatment: (1) Short-acting bronchodilators — ipratropium + albuterol nebulization q4-6h; (2) Systemic corticosteroids — prednisone 40mg daily × 5 days (no difference between 5 and 14 days); (3) Antibiotics — if purulent sputum, increased dyspnea, or increased sputum volume (Anthonisen criteria): amoxicillin-clavulanate, doxycycline, or azithromycin for mild; fluoroquinolone for severe/hospitalized. (4) Respiratory support: BiPAP if acute hypercapnic failure (pH <7.35). Target SpO2 88-92% (not higher — prevents hypoxic drive suppression and Haldane effect).
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