Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Internal Medicine and Medical Subspecialties Syllabus

What pulmonary function test finding is characteristic of idiopathic pulmonary fibrosis?

A restrictive pattern (reduced FVC and TLC with normal/high FEV1/FVC) plus a markedly reduced DLCO; HRCT shows usual interstitial pneumonia with subpleural honeycombing.

Give the Henderson-Hasselbalch / Winter's formula for expected PaCO2 compensation in metabolic acidosis.

Winter's formula: expected PaCO2 = (1.5 x HCO3-) + 8 +/- 2. If measured PaCO2 is higher, there is a concurrent respiratory acidosis; if lower, a concurrent respiratory alkalosis.

How do you calculate the anion gap and what is the mnemonic for a high anion gap metabolic acidosis?

Anion gap = Na+ - (Cl- + HCO3-); normal ~8-12. High-gap causes: MUDPILES (Methanol, Uremia, DKA, Propylene glycol, Iron/INH, Lactic acidosis, Ethylene glycol, Salicylates).

What ECG changes and acute treatment are associated with severe hyperkalemia?

ECG: peaked T waves, then widened QRS, PR prolongation, loss of P waves, sine wave. Treatment: IV calcium gluconate (membrane stabilization), then insulin+glucose and beta-agonists (shift), then dialysis/diuretics/binders (elimination).

How do you distinguish prerenal AKI from intrinsic (ATN) AKI using BUN/Cr ratio and FENa?

Prerenal: BUN/Cr >20:1, FENa <1%, urine osmolality >500, bland sediment. ATN (intrinsic): BUN/Cr ~10-15:1, FENa >2%, urine osmolality ~300, muddy brown granular casts.

What defines chronic kidney disease and what GFR defines each stage G1-G5?

CKD = GFR <60 or kidney damage markers for >=3 months. Stages: G1 >=90 (with damage), G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, G5 <15 (kidney failure).

What are the diagnostic glycemic criteria for diabetes mellitus?

HbA1c >=6.5%, fasting plasma glucose >=126 mg/dL, 2-hour OGTT glucose >=200 mg/dL, or random glucose >=200 mg/dL with classic symptoms. (Prediabetes: A1c 5.7-6.4%, FPG 100-125.)

Distinguish DKA from hyperosmolar hyperglycemic state (HHS).

DKA (usually type 1): glucose ~250-600, marked ketoacidosis (pH <7.3, high anion gap), moderate hyperosmolality. HHS (usually type 2): glucose >600, minimal/no ketones, pH >7.3, severe hyperosmolality (>320) and profound dehydration; higher mortality.

Compare lab findings (TSH, free T4) in primary hyperthyroidism, primary hypothyroidism, and central hypothyroidism.

Primary hyperthyroid: low TSH, high free T4. Primary hypothyroid: high TSH, low free T4. Central (secondary) hypothyroid: low/inappropriately normal TSH with low free T4.

What are the lab findings and confirmatory test for primary adrenal insufficiency (Addison disease)?

Low cortisol, high ACTH, hyponatremia, hyperkalemia, hypoglycemia, and hyperpigmentation. Confirmed with the cosyntropin (ACTH) stimulation test showing a blunted cortisol response.

How do you differentiate Cushing disease from ectopic ACTH syndrome and adrenal Cushing's?

Cushing disease (pituitary ACTH adenoma): high ACTH, suppresses with high-dose dexamethasone. Ectopic ACTH: high ACTH, no suppression. Adrenal tumor: low ACTH (ACTH-independent), no suppression.

What hormone abnormality causes acromegaly and what is the best screening test?

Excess growth hormone (usually from a pituitary adenoma) acting via IGF-1. Best screening test: elevated serum IGF-1; confirm with failure of GH to suppress during an oral glucose tolerance test.

What are the alarm features in GERD that warrant endoscopy, and what complication is Barrett esophagus?

Alarm features: dysphagia, odynophagia, weight loss, GI bleeding/anemia, vomiting, age >50 with new symptoms. Barrett esophagus is metaplasia of esophageal squamous to intestinal columnar epithelium, a precursor to adenocarcinoma.

Contrast gastric and duodenal peptic ulcers by relationship of pain to meals.

Gastric ulcer: pain worsens with eating (weight loss). Duodenal ulcer: pain improves with eating and worsens 2-3 hours after meals or at night (weight gain). Both are commonly H. pylori or NSAID related.

What is the triple therapy regimen for Helicobacter pylori eradication?

A proton pump inhibitor plus clarithromycin plus amoxicillin (or metronidazole if penicillin-allergic) for 14 days. Bismuth quadruple therapy is used in high clarithromycin-resistance areas.

Differentiate Crohn disease from ulcerative colitis by distribution and histology.

Crohn: skip lesions anywhere mouth-to-anus (often terminal ileum), transmural inflammation, non-caseating granulomas, fistulas/strictures. UC: continuous involvement from rectum proximally, mucosa/submucosa only, no granulomas, crypt abscesses, increased colon cancer risk.

Distinguish celiac disease serology and the gold-standard diagnostic test.

Serology: anti-tissue transglutaminase (tTG) IgA (with total IgA). Gold standard: duodenal biopsy showing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Associated with HLA-DQ2/DQ8 and dermatitis herpetiformis.

What pattern of liver enzymes suggests hepatocellular versus cholestatic injury?

Hepatocellular: predominant AST/ALT elevation (AST:ALT >2 suggests alcohol). Cholestatic: predominant alkaline phosphatase and GGT elevation with bilirubin (biliary obstruction/PBC/PSC).

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

Charcot's triad: fever, RUQ pain, jaundice. Reynolds' pentad adds hypotension and altered mental status, indicating suppurative cholangitis requiring urgent biliary decompression.

What are Ranson's criteria used for and name two on-admission markers of severe acute pancreatitis?

Ranson's criteria estimate severity/mortality of acute pancreatitis. On-admission markers include age >55, WBC >16,000, glucose >200, AST >250, and LDH >350.

How do you clinically distinguish upper from lower GI bleeding?

Upper GI bleed (proximal to ligament of Treitz): hematemesis, coffee-ground emesis, melena, elevated BUN/Cr ratio. Lower GI bleed: hematochezia (bright red blood per rectum), though brisk upper bleeds can also cause hematochezia.

What is the initial management priority and key pharmacologic agents in variceal upper GI hemorrhage?

Resuscitation (IV fluids/blood, two large-bore IVs), then octreotide (splanchnic vasoconstriction), IV PPI, prophylactic antibiotics (ceftriaxone), and urgent endoscopy with band ligation.

Classify anemia by MCV and give one cause in each category.

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

What lab profile distinguishes 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 TIBC, with elevated hepcidin.

Compare sickle cell disease and the alpha/beta thalassemias by underlying defect.

Sickle cell: point mutation (Glu->Val) in beta-globin causing HbS polymerization/vaso-occlusion. Thalassemias: reduced quantity of normal globin chains (alpha = deletions of alpha genes; beta = mutations reducing beta-chain synthesis) causing microcytic anemia.

What coagulation test abnormalities are seen in hemophilia A versus von Willebrand disease?

Hemophilia A (factor VIII deficiency, X-linked): prolonged aPTT, normal PT, normal platelets/bleeding time. von Willebrand disease: prolonged aPTT (low VIII) +/- prolonged bleeding time/abnormal platelet function, with mucocutaneous bleeding; most common inherited bleeding disorder.

What lab pattern (PT, aPTT, platelets, fibrinogen, D-dimer) defines disseminated intravascular coagulation?

Prolonged PT and aPTT, low platelets, low fibrinogen, and elevated D-dimer (with schistocytes on smear), reflecting simultaneous consumption of clotting factors and fibrinolysis.

Distinguish Hodgkin from non-Hodgkin lymphoma, including the pathognomonic cell.

Hodgkin lymphoma: Reed-Sternberg cells (CD15+/CD30+), contiguous nodal spread, bimodal age, often with B symptoms; better prognosis. Non-Hodgkin: more heterogeneous, often disseminated/extranodal, B- or T-cell origin.

What translocations are classically associated with CML and Burkitt lymphoma?

CML: t(9;22) Philadelphia chromosome (BCR-ABL fusion), treated with tyrosine kinase inhibitors like imatinib. Burkitt lymphoma: t(8;14) (c-MYC), 'starry sky' appearance on histology.

What autoantibodies are associated with systemic lupus erythematosus, and which are most specific?

ANA is sensitive (screening). Most specific: anti-dsDNA (correlates with disease activity/nephritis) and anti-Smith. Anti-histone antibodies suggest drug-induced lupus.

Differentiate rheumatoid arthritis from osteoarthritis by joint involvement and stiffness pattern.

RA: symmetric small-joint inflammation (MCP, PIP, wrists), morning stiffness >1 hour, RF/anti-CCP positive, spares DIP. OA: asymmetric, weight-bearing/DIP joints (Heberden nodes), brief (<30 min) stiffness, worse with use.

What antibody and clinical features characterize systemic sclerosis (scleroderma), including the CREST syndrome?

Diffuse: anti-Scl-70 (topoisomerase I). Limited (CREST): anti-centromere antibody. CREST = Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias.

What are the most common bacterial causes of community-acquired pneumonia and the empiric outpatient treatment?

Streptococcus pneumoniae is most common (also H. influenzae, atypicals like Mycoplasma). Outpatient empiric: a macrolide or doxycycline (or a respiratory fluoroquinolone / beta-lactam + macrolide if comorbidities).

What organisms cause uncomplicated cystitis and what is first-line therapy?

Most commonly E. coli (also Klebsiella, Proteus, Staphylococcus saprophyticus). First-line: nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin.

What CSF findings distinguish bacterial from viral meningitis?

Bacterial: high opening pressure, neutrophilic pleocytosis (high WBC), low glucose, high protein. Viral: lymphocytic pleocytosis, normal glucose, mildly elevated protein.

At what CD4 count do you start prophylaxis for Pneumocystis jirovecii and what agent is used?

Start PCP prophylaxis when CD4 <200 cells/mm3 (or oropharyngeal candidiasis); first-line is trimethoprim-sulfamethoxazole.

Match HIV opportunistic infections to their CD4 thresholds: PCP, Toxoplasmosis, MAC, CMV retinitis.

PCP: CD4 <200. Toxoplasma encephalitis: CD4 <100. CMV retinitis and disseminated MAC: CD4 <50.

What is the time-window and mechanism of tPA (alteplase) for acute ischemic stroke?

IV alteplase (a thrombolytic that activates plasminogen to dissolve clot) is given within 4.5 hours of symptom onset after hemorrhage is excluded by CT and contraindications are checked.

Distinguish the headache features of migraine, cluster, and tension-type headache.

Migraine: unilateral, pulsating, moderate-severe, photophobia/phonophobia/nausea, +/- aura, lasts 4-72 hours. Cluster: severe unilateral orbital pain with ipsilateral autonomic signs (tearing, rhinorrhea, ptosis), short attacks in clusters. Tension: bilateral, band-like, pressing, mild-moderate, no nausea.

What clinical features distinguish a focal seizure with impaired awareness from a generalized tonic-clonic seizure?

Focal impaired-awareness: starts in one hemisphere, automatisms, altered/impaired consciousness, often with postictal confusion, may have aura. Generalized tonic-clonic: bilateral from onset, loss of consciousness, tonic stiffening then clonic jerking, tongue-biting/incontinence, postictal state.

Contrast the core motor and cognitive features of Parkinson disease and Alzheimer disease.

Parkinson: resting tremor, bradykinesia, cogwheel rigidity, postural instability from dopaminergic nigrostriatal loss. Alzheimer: progressive anterograde memory loss then global cognitive decline, with amyloid plaques and neurofibrillary (tau) tangles.