United States Medical Licensing Examination (USMLE) Internal Medicine and Clinical Knowledge (Step 2 CK) Syllabus

What is the Wells criteria-based diagnostic pathway for suspected pulmonary embolism?

Low/intermediate probability (Wells <=4): obtain D-dimer-if negative, PE excluded; if positive, do CT pulmonary angiography. High probability (Wells >4): go directly to CTPA. Use V/Q scan if contrast/contraindication to CT (e.g., renal failure).

What is the treatment of acute pulmonary embolism, including the indication for thrombolysis?

Anticoagulation (LMWH/DOAC, or heparin if unstable). Thrombolysis (e.g., tPA) is indicated for massive PE with hemodynamic instability (hypotension). Submassive PE with RV strain may be considered for thrombolysis/embolectomy. IVC filter if anticoagulation is contraindicated.

How does Light's criteria differentiate exudative from transudative pleural effusions?

Exudate if ANY of: pleural/serum protein ratio >0.5; pleural/serum LDH ratio >0.6; or pleural LDH >2/3 the upper limit of serum LDH. Transudates (CHF, cirrhosis, nephrotic syndrome) meet none; exudates suggest infection, malignancy, or PE.

What pleural fluid findings indicate a complicated parapneumonic effusion/empyema requiring chest tube drainage?

Pleural fluid pH <7.2, glucose <60 mg/dL, positive Gram stain/culture, or frank pus. These require tube thoracostomy drainage in addition to antibiotics.

What are the Sepsis-3 definitions of sepsis and septic shock?

Sepsis: life-threatening organ dysfunction (SOFA increase >=2) due to dysregulated host response to infection. Septic shock: sepsis with vasopressor requirement to maintain MAP >=65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation.

What are the key components of the initial sepsis resuscitation ('Hour-1') bundle?

Measure lactate, obtain blood cultures before antibiotics, give broad-spectrum antibiotics, administer 30 mL/kg crystalloid for hypotension or lactate >=4, and start vasopressors (norepinephrine first-line) if hypotensive during/after fluids to maintain MAP >=65.

How are the four main shock types distinguished by cardiac output, SVR, and preload (CVP/PCWP)?

Hypovolemic: low CO, high SVR, low preload. Cardiogenic: low CO, high SVR, high preload. Obstructive (PE/tamponade): low CO, high SVR, variable/high preload. Distributive (septic/anaphylactic): high CO, low SVR, low preload.

What is the initial approach to acute upper GI bleeding and the role of risk stratification?

Resuscitate (two large-bore IVs, fluids, transfuse to Hgb ~7 g/dL restrictive threshold), IV PPI, and upper endoscopy within 24h. For suspected variceal bleed add octreotide and prophylactic antibiotics (ceftriaxone). Glasgow-Blatchford score identifies low-risk patients for outpatient management.

How do you differentiate upper from lower GI bleeding and what initial test helps?

Upper GI bleed (proximal to ligament of Treitz): hematemesis, melena, elevated BUN:Cr ratio (>20-30). Lower GI bleed: hematochezia. A nasogastric aspirate or upper endoscopy can confirm upper source; melena suggests upper but can be right colon.

What are the key distinguishing features between Crohn disease and ulcerative colitis?

Crohn: transmural, skip lesions anywhere mouth-to-anus (terminal ileum common), non-caseating granulomas, fistulae/strictures, cobblestoning. UC: continuous mucosal inflammation from rectum proximally, limited to colon, crypt abscesses, increased colon cancer risk, associated with PSC; curable by colectomy.

What is the general treatment escalation ('step-up') for inflammatory bowel disease?

5-ASA (mesalamine, mainly UC) -> corticosteroids for flares -> immunomodulators (azathioprine, 6-MP, methotrexate) -> biologics (anti-TNF like infliximab, anti-integrin vedolizumab, anti-IL-12/23 ustekinumab). Surgery is curative for UC.

What is the diagnostic workup and management of spontaneous bacterial peritonitis (SBP) in cirrhosis?

Diagnostic paracentesis showing ascitic fluid PMN count >=250 cells/mm3. Treat empirically with IV third-generation cephalosporin (cefotaxime) plus IV albumin (to reduce renal failure/mortality). Give long-term fluoroquinolone prophylaxis after an episode.

What is hepatic encephalopathy and its first-line treatment?

Reversible neuropsychiatric dysfunction from accumulated nitrogenous toxins (ammonia) in liver failure, often with asterixis. First-line: lactulose (titrated to 2-3 soft stools/day); add rifaximin for recurrence. Identify and treat precipitants (GI bleed, infection, constipation, electrolyte disturbance).

How is the severity and gradient of ascites assessed, and what does SAAG indicate?

Serum-ascites albumin gradient (SAAG) = serum albumin - ascites albumin. SAAG >=1.1 g/dL indicates portal hypertension (cirrhosis, heart failure, Budd-Chiari). SAAG <1.1 suggests non-portal causes (malignancy, TB, pancreatitis, nephrotic syndrome).

What are the diagnostic criteria for acute pancreatitis (2 of 3) and the main management?

Diagnosis requires >=2 of: (1) characteristic epigastric pain radiating to back; (2) lipase/amylase >=3x upper limit normal; (3) imaging findings. Management: aggressive IV fluids, analgesia, early enteral nutrition; most common causes are gallstones and alcohol.

What is Charcot's triad and Reynolds' pentad in acute cholangitis, and the management?

Charcot's triad: fever, RUQ pain, jaundice. Reynolds' pentad adds hypotension and altered mental status (suppurative cholangitis). Management: IV antibiotics, fluids, and urgent biliary decompression via ERCP.

What are the Rome IV-based diagnostic features and management of irritable bowel syndrome (IBS)?

Recurrent abdominal pain >=1 day/week for 3 months associated with defecation and/or change in stool frequency/form, without alarm features. Management is symptom-based: fiber/antispasmodics, IBS-C (linaclotide/lubiprostone), IBS-D (loperamide, rifaximin); evaluate alarm features (weight loss, bleeding, anemia, age >50).

At what age and intervals is average-risk colorectal cancer screening recommended, and what are the options?

Begin at age 45 (USPSTF). Options: colonoscopy every 10 years, FIT annually, FIT-DNA every 1-3 years, CT colonography every 5 years, or flexible sigmoidoscopy every 5 years. Continue through age 75 (individualize 76-85).

What distinguishes diabetic ketoacidosis (DKA) from hyperosmolar hyperglycemic state (HHS)?

DKA (usually T1DM): glucose >250, pH <7.3, bicarbonate <18, positive ketones, anion gap acidosis. HHS (usually T2DM): glucose often >600, osmolality >320, minimal/no ketones, pH >7.3, profound dehydration, altered mental status. Both treated with IV fluids, insulin, and potassium repletion.

What is the correct sequence and key safety points of DKA management?

IV isotonic fluids first; check potassium-if K <3.3, hold insulin and replete K first; start IV insulin infusion; add potassium when K <5.3 with urine output; switch fluids to D5-containing when glucose ~200; continue insulin until anion gap closes and overlap with subcutaneous insulin before stopping the drip.

How is primary versus secondary hyperthyroidism interpreted, and what is the treatment of thyroid storm?

Primary hyperthyroidism: low TSH, high free T4 (e.g., Graves). Thyroid storm treatment order: beta-blocker (propranolol), thionamide (PTU preferred), then iodine (Lugol's) at least 1 hour after thionamide, plus glucocorticoids; treat precipitant and provide supportive care.

How do you diagnose primary adrenal insufficiency (Addison) and manage adrenal crisis?

Diagnosis: low morning cortisol with inappropriately high ACTH and inadequate response to cosyntropin (ACTH) stimulation test; hyponatremia + hyperkalemia. Adrenal crisis treatment: immediate IV hydrocortisone, aggressive IV normal saline, and dextrose; do not delay steroids for testing.

How do you calculate the corrected sodium in hyperglycemia and the free water deficit in hypernatremia?

Corrected Na = measured Na + 1.6 (or 2.4) x [(glucose - 100)/100]. Free water deficit = total body water x [(serum Na/140) - 1], where TBW = 0.6 x weight(kg) in men (0.5 in women). Correct chronic hypernatremia slowly (<10-12 mEq/L per 24h).

What is the danger of overly rapid correction of hyponatremia, and the safe correction rate?

Overly rapid correction risks osmotic demyelination syndrome (central pontine myelinolysis). Limit correction to <=8 mEq/L per 24 hours (more conservative, ~6, in high-risk patients). For severe symptomatic hyponatremia, give 3% hypertonic saline boluses to raise Na ~4-6 mEq acutely.

How do you interpret a primary metabolic acidosis using the anion gap and Winter's formula?

Anion gap = Na - (Cl + HCO3); normal ~12. High anion gap acidosis (MUDPILES). Winter's formula predicts respiratory compensation: expected PaCO2 = 1.5 x HCO3 + 8 (+/-2). Measured PaCO2 above expected = concurrent respiratory acidosis; below = concurrent respiratory alkalosis.

How are the categories of acute kidney injury (prerenal, intrinsic, postrenal) distinguished by FENa and urine findings?

Prerenal: FENa <1%, BUN:Cr >20, bland sediment, concentrated urine (Uosm >500). Intrinsic (ATN): FENa >2%, muddy brown granular casts, isosthenuria. Postrenal: obstruction on imaging (hydronephrosis). FEurea <35% is useful for prerenal if on diuretics.

What are the emergent (AEIOU) indications for dialysis in acute kidney injury?

Acidosis (refractory metabolic), Electrolytes (refractory hyperkalemia), Intoxications (dialyzable toxins-methanol, ethylene glycol, salicylates, lithium), Overload (refractory volume overload/pulmonary edema), Uremia (encephalopathy, pericarditis, bleeding).

How is chronic kidney disease staged by GFR, and what are the cornerstones of management?

G1 >=90, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, G5 <15 (with albuminuria categories A1-A3). Management: ACE inhibitor/ARB for proteinuria, SGLT2 inhibitor, BP and glycemic control, manage anemia (EPO/iron), mineral-bone disease (phosphate binders, vitamin D), and avoid nephrotoxins.

What is the difference between empiric and definitive (de-escalation) antimicrobial therapy in stewardship?

Empiric therapy: broad-spectrum coverage started before culture results based on likely pathogens/site. Definitive therapy: narrow the spectrum once culture and susceptibility data return (de-escalation), choosing the narrowest effective agent for the shortest effective duration to limit resistance and toxicity.

At what CD4 count do major opportunistic infections occur in HIV, and what prophylaxis is given?

CD4 <200: Pneumocystis jirovecii pneumonia-prophylax with TMP-SMX. CD4 <100: Toxoplasma (also TMP-SMX). CD4 <50: Mycobacterium avium complex (historically azithromycin, now often deferred with ART) and CMV retinitis. Start antiretroviral therapy in all HIV patients.

What is the empiric treatment and key diagnostic of Pneumocystis jirovecii pneumonia (PCP)?

Presents with subacute dyspnea, dry cough, hypoxia, and elevated LDH; diffuse bilateral interstitial infiltrates. Treat with TMP-SMX; add adjunctive corticosteroids if PaO2 <70 mmHg or A-a gradient >=35 mmHg. Diagnosis via induced sputum/BAL with silver stain or PCR.

How are hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) defined and treated?

HAP: pneumonia >=48h after admission; VAP: >=48h after intubation. Empiric therapy must cover MRSA (vancomycin/linezolid) and Pseudomonas (e.g., piperacillin-tazobactam, cefepime), with double anti-pseudomonal coverage if high resistance risk or septic shock.

What is the diagnostic approach and treatment for Clostridioides difficile infection?

Diagnose with stool PCR/toxin testing in patients with >=3 unformed stools/24h. First-line treatment: oral vancomycin or fidaxomicin (oral metronidazole only if non-severe and alternatives unavailable). Stop the inciting antibiotic; fulminant cases need oral vancomycin + IV metronidazole +/- surgery.

What is tumor lysis syndrome, its lab findings, and management?

Massive tumor cell breakdown (often after chemo of high-grade lymphoma/leukemia) causing hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia, risking AKI and arrhythmia. Management: aggressive IV hydration, rasburicase (or allopurinol for prophylaxis), and treat electrolyte abnormalities.

What is the presentation and emergent management of malignant spinal cord compression?

Back pain (often worse when lying down), progressive weakness, sensory level, and bowel/bladder dysfunction in a cancer patient. Give immediate IV dexamethasone and obtain urgent whole-spine MRI, followed by radiation oncology/neurosurgery for definitive decompression.

How is anemia classified by MCV, with key examples in each category?

Microcytic (MCV <80): iron deficiency, thalassemia, anemia of chronic disease (late), sideroblastic. Normocytic (80-100): acute blood loss, hemolysis, anemia of chronic disease, CKD. Macrocytic (MCV >100): B12/folate deficiency (megaloblastic), alcohol, liver disease, hypothyroidism, drugs.

How do iron studies differentiate iron deficiency anemia from anemia of chronic disease?

Iron deficiency: low ferritin, low serum iron, HIGH TIBC, low transferrin saturation. Anemia of chronic disease: normal/high ferritin, low serum iron, LOW/normal TIBC, often normal/low transferrin saturation due to iron sequestration.

What lab pattern identifies disseminated intravascular coagulation (DIC)?

Prolonged PT and aPTT, low fibrinogen, elevated D-dimer/fibrin degradation products, and thrombocytopenia, with schistocytes on smear. Treat the underlying cause; support with platelets, FFP, and cryoprecipitate (for low fibrinogen) as needed for bleeding.

What are the diagnostic features and first-line treatment of systemic lupus erythematosus (SLE)?

Multisystem autoimmune disease with malar rash, arthritis, serositis, nephritis, cytopenias; positive ANA (sensitive) and anti-dsDNA/anti-Smith (specific). Monitor disease with complement (C3/C4) and dsDNA. Treatment: hydroxychloroquine for all, with corticosteroids/immunosuppressants for organ involvement (e.g., lupus nephritis).

How is giant cell (temporal) arteritis diagnosed and managed urgently?

Older patient with new headache, jaw claudication, scalp tenderness, visual changes, and markedly elevated ESR/CRP, often with polymyalgia rheumatica. Start high-dose corticosteroids IMMEDIATELY (do not wait for biopsy) to prevent irreversible blindness; confirm with temporal artery biopsy.

What synovial fluid features distinguish inflammatory, septic, and crystal arthritis?

Non-inflammatory: WBC <2,000. Inflammatory: WBC 2,000-50,000. Septic: WBC >50,000 (often >75,000), high PMNs, positive Gram stain/culture. Gout: negatively birefringent needle-shaped (monosodium urate) crystals; pseudogout: positively birefringent rhomboid (calcium pyrophosphate) crystals.

How is rheumatoid arthritis distinguished from osteoarthritis clinically and serologically?

RA: symmetric inflammatory polyarthritis of MCP/PIP/wrists with morning stiffness >1h, positive RF and anti-CCP, elevated ESR/CRP, erosions on X-ray; spares DIPs. OA: asymmetric, weight-bearing/DIP joints, brief stiffness, no systemic inflammation, osteophytes and joint-space narrowing on X-ray.

What is the time-sensitive treatment of acute ischemic stroke, including the tPA and thrombectomy windows?

IV thrombolysis (alteplase/tenecteplase) within 4.5 hours of symptom onset after excluding hemorrhage with non-contrast CT. Mechanical thrombectomy for large-vessel occlusion up to 24 hours in selected patients with favorable perfusion imaging. Maintain permissive hypertension unless giving tPA (then BP <185/110).

How do you differentiate a TIA from a stroke, and what is secondary prevention?

TIA: transient neurologic deficit from ischemia WITHOUT acute infarction on imaging (deficits typically resolve within an hour). Stroke: deficit with infarction. Secondary prevention: antiplatelet therapy (aspirin, or short-term dual antiplatelet for high-risk TIA/minor stroke), high-intensity statin, BP control, and carotid endarterectomy if stenosis 70-99% symptomatic.

What defines status epilepticus and what is the stepwise treatment?

Continuous seizure >=5 minutes or recurrent seizures without recovery between them. Step 1: IV benzodiazepine (lorazepam). Step 2: IV antiseizure agent (levetiracetam, fosphenytoin, or valproate). Step 3 (refractory): anesthetic infusion (midazolam, propofol) with intubation; check glucose and treat reversible causes.

What headache features are 'red flags' requiring urgent imaging?

Thunderclap (worst-ever, sudden) headache, focal neurologic deficit, papilledema, headache with fever/neck stiffness, onset after age 50, immunosuppression/cancer, headache worse with Valsalva/positional, or progressive worsening. A thunderclap headache mandates CT and possibly LP to rule out subarachnoid hemorrhage.

How is Parkinson disease characterized and treated, and what distinguishes essential tremor?

Parkinson: bradykinesia plus resting (pill-rolling) tremor, cogwheel rigidity, and postural instability; treat with levodopa-carbidopa (or dopamine agonists). Essential tremor: bilateral ACTION/postural tremor improved by alcohol, often familial, treated with propranolol or primidone-no rest tremor or rigidity.