Medical Council Step exam for International Medical Graduates / ECFMG Certification USMLE Step 1: Foundational & Basic Sciences Syllabus

Distinguish labile, stable, and permanent tissues with respect to regenerative capacity.

Labile: continuously dividing (gut epithelium, skin, bone marrow). Stable (quiescent, G0): divide when stimulated (hepatocytes, renal tubules). Permanent: cannot regenerate (neurons, cardiac and skeletal muscle) -> heal by scar.

What is the difference between a benign and malignant neoplasm in terms of nomenclature and behavior?

Benign: well-differentiated, slow-growing, encapsulated, no metastasis (suffix -oma). Malignant: poorly differentiated/anaplastic, invasive, metastasizing (carcinoma = epithelial; sarcoma = mesenchymal).

Define the hallmarks: dysplasia, carcinoma in situ, and invasive carcinoma.

Dysplasia: disordered, abnormal but reversible cellular growth, no basement membrane invasion. Carcinoma in situ: full-thickness dysplasia, basement membrane intact. Invasive carcinoma: malignant cells breach the basement membrane and can metastasize.

Give two classic examples each of oncogenes and tumor suppressor genes and the cancers associated.

Oncogenes (gain of function): RAS (many carcinomas), MYC (Burkitt lymphoma), HER2/neu (breast). Tumor suppressors (loss of function, two-hit): TP53 (Li-Fraumeni, many cancers), RB (retinoblastoma, osteosarcoma).

What is the difference between paraneoplastic syndromes from small cell lung cancer producing ADH vs. ACTH?

Ectopic ADH (SIADH) causes hyponatremia. Ectopic ACTH causes Cushing syndrome (hypertension, hyperglycemia, hypokalemia). Both are paraneoplastic and classically caused by small cell lung carcinoma.

Distinguish transudate from exudate in edema, including protein content and specific gravity.

Transudate: low protein, specific gravity <1.012, due to increased hydrostatic or decreased oncotic pressure (e.g., CHF, cirrhosis). Exudate: high protein/cells, specific gravity >1.020, due to inflammation/increased vascular permeability.

What are the three components of Virchow's triad for thrombosis?

1) Endothelial injury, 2) Stasis/abnormal blood flow, and 3) Hypercoagulability.

Compare the four major types of shock (hypovolemic, cardiogenic, distributive, obstructive) by preload, cardiac output, and SVR.

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

What is a fat embolism, and what is its classic clinical triad?

Fat embolism follows long bone/pelvic fractures or liposuction; classic triad = hypoxemia (respiratory distress), neurologic abnormalities (confusion), and petechial rash.

Describe the difference between Gram-positive and Gram-negative bacterial cell walls and how this affects Gram staining.

Gram-positive: thick peptidoglycan layer retains crystal violet -> stains purple. Gram-negative: thin peptidoglycan plus an outer membrane with LPS (endotoxin); crystal violet washes out, counterstain safranin -> stains pink/red.

Compare exotoxins and endotoxin.

Exotoxins: secreted proteins from Gram+ and Gram- bacteria, high potency, often have specific actions, can be made into toxoids, heat-labile. Endotoxin (LPS): outer membrane component of Gram-negative bacteria only, released on lysis, induces fever/shock/DIC via macrophage activation, heat-stable, no toxoid.

Which bacteria are obligate intracellular and obligate aerobes (give the classic mnemonic organisms)?

Obligate intracellular (need host ATP): Rickettsia, Chlamydia (and Coxiella). Obligate aerobes: Nocardia, Pseudomonas, MycoBacterium tuberculosis, Bacillus (mnemonic 'Nagging Pests Must Breathe').

What is the mechanism of diphtheria and Pseudomonas exotoxin A?

Both ADP-ribosylate elongation factor 2 (EF-2), inhibiting host cell protein synthesis. Diphtheria toxin -> pseudomembranous pharyngitis and myocarditis.

Differentiate DNA from RNA viruses by genome features and the classic exceptions.

Most DNA viruses are double-stranded, linear, enveloped or naked, and replicate in the nucleus (except poxvirus = cytoplasm). Most RNA viruses are single-stranded and replicate in the cytoplasm (except influenza and retroviruses). Positive-sense ssRNA is directly translatable; negative-sense ssRNA must carry an RNA-dependent RNA polymerase.

What enzyme do retroviruses (e.g., HIV) use, and what are HIV's three structural genes?

Reverse transcriptase (RNA-dependent DNA polymerase). The three structural genes are gag (capsid p24), pol (reverse transcriptase, integrase, protease), and env (gp120/gp41 envelope glycoproteins).

Define antigenic drift versus antigenic shift in influenza.

Antigenic drift: minor point mutations in hemagglutinin/neuraminidase causing seasonal epidemics. Antigenic shift: reassortment of segmented genomes between strains causing major changes and pandemics.

Which fungus causes which disease: Cryptococcus, Pneumocystis jirovecii, Candida, and Aspergillus in immunocompromised hosts?

Cryptococcus neoformans: meningitis (India ink/encapsulated, soap-bubble lesions). Pneumocystis jirovecii: interstitial pneumonia (silver stain, treat TMP-SMX). Candida albicans: thrush/esophagitis/disseminated. Aspergillus fumigatus: invasive aspergillosis/ABPA (septate hyphae branching at 45 degrees).

Match the parasite to its key feature: Plasmodium, Giardia, Toxoplasma, and Entamoeba histolytica.

Plasmodium: malaria, cyclic fevers, Anopheles mosquito vector. Giardia lamblia: fatty diarrhea after camping/contaminated water. Toxoplasma gondii: cat feces/undercooked meat, ring-enhancing brain lesions in AIDS, congenital chorioretinitis. Entamoeba histolytica: bloody dysentery + flask-shaped liver abscess.

Compare the four hypersensitivity reactions with mechanism and an example each.

Type I: IgE-mediated, immediate (anaphylaxis, allergy). Type II: antibody (IgG/IgM) against fixed cell-surface antigens (autoimmune hemolytic anemia, Goodpasture). Type III: immune complex deposition (SLE, serum sickness). Type IV: T-cell mediated, delayed (PPD test, contact dermatitis, transplant rejection).

Which interleukins and cell types define Th1 vs Th2 helper T-cell responses?

Th1: driven by IL-12, secretes IFN-gamma; activates macrophages and cytotoxic T cells (cell-mediated immunity/intracellular pathogens). Th2: driven by IL-4, secretes IL-4, IL-5, IL-10, IL-13; promotes B-cell antibody/IgE production and eosinophils (parasites/allergy).

Distinguish the functions of MHC class I and MHC class II.

MHC I (HLA-A, B, C): on all nucleated cells, presents endogenous (intracellular/viral) peptides to CD8+ cytotoxic T cells. MHC II (HLA-DR, DP, DQ): on antigen-presenting cells, presents exogenous peptides to CD4+ helper T cells.

In pharmacokinetics, write the formulas for volume of distribution, clearance, and half-life.

Vd = amount of drug in body / plasma drug concentration. Clearance (CL) = rate of elimination / plasma concentration = 0.693 x Vd / t1/2. Half-life t1/2 = 0.693 x Vd / CL.

Differentiate zero-order from first-order elimination kinetics, with drug examples.

Zero-order: a constant amount eliminated per time (capacity-limited), independent of concentration -> Phenytoin, Ethanol, Aspirin (high dose) ('PEA'). First-order: a constant fraction eliminated per time, proportional to concentration (most drugs).

Define loading dose and maintenance dose formulas.

Loading dose = (Cp target x Vd) / bioavailability (F). Maintenance dose = (Cp target x CL x dosing interval) / F. Loading dose is unchanged in renal/hepatic disease; maintenance dose is reduced.

Explain the difference between a competitive and noncompetitive antagonist on potency (EC50) and efficacy (Vmax/Emax).

Competitive antagonist: surmountable, shifts the dose-response curve right (decreased potency, increased EC50) with no change in maximal efficacy. Noncompetitive antagonist: insurmountable, decreases maximal efficacy (decreased Emax/Vmax) with potency unchanged.

Compare the effects of activating the sympathetic vs parasympathetic nervous system on heart rate, pupils, bronchi, and GI motility.

Sympathetic (fight/flight): increased HR, mydriasis (pupil dilation), bronchodilation, decreased GI motility. Parasympathetic (rest/digest): decreased HR, miosis (pupil constriction), bronchoconstriction, increased GI motility/secretions.

Match the autonomic receptor to its primary action: alpha-1, alpha-2, beta-1, beta-2, and M3.

Alpha-1: vasoconstriction, mydriasis, increased bladder sphincter tone. Alpha-2: decreased sympathetic outflow/decreased norepinephrine release. Beta-1: increased heart rate, contractility, and renin release. Beta-2: vasodilation, bronchodilation, uterine relaxation. M3: increased exocrine secretions, smooth muscle contraction, miosis.

Compare CYP450 inducers and inhibitors with classic examples, and the effect on coadministered drug levels.

Inducers (increase metabolism -> lower drug levels): rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort, chronic alcohol, griseofulvin. Inhibitors (decrease metabolism -> higher drug levels/toxicity): cimetidine, ketoconazole, macrolides (erythromycin), grapefruit juice, ritonavir, isoniazid, fluoroquinolones.

Differentiate Phase I and Phase II drug metabolism.

Phase I: reduction, oxidation, hydrolysis (mostly CYP450) yielding slightly polar, often still-active metabolites; diminished first in elderly. Phase II: conjugation (glucuronidation, acetylation, sulfation) yielding very polar, usually inactive, water-soluble metabolites for excretion.

Give the antidotes for: acetaminophen, opioids, benzodiazepines, warfarin, and organophosphate poisoning.

Acetaminophen: N-acetylcysteine. Opioids: naloxone. Benzodiazepines: flumazenil. Warfarin: vitamin K (acute reversal with fresh frozen plasma/PCC). Organophosphates: atropine + pralidoxime.

In epidemiology, write the formulas for sensitivity, specificity, PPV, and NPV.

Sensitivity = TP/(TP+FN) (true positives among diseased). Specificity = TN/(TN+FP) (true negatives among healthy). PPV = TP/(TP+FP) (proportion with positive test who have disease). NPV = TN/(TN+FN). PPV and NPV vary with disease prevalence; sensitivity/specificity do not.

Differentiate relative risk (RR), odds ratio (OR), and attributable risk (AR), and which study design uses each.

RR = risk in exposed / risk in unexposed (cohort studies). OR = (a/b)/(c/d) = ad/bc, approximates RR in case-control studies (used when incidence is unknown). AR = risk in exposed - risk in unexposed (excess risk due to exposure).

Define Type I and Type II error, alpha, beta, and statistical power.

Type I error (alpha): rejecting a true null hypothesis (false positive). Type II error (beta): failing to reject a false null (false negative). Power = 1 - beta = probability of correctly detecting a true effect; increases with larger sample size and effect size.

What is the difference between confounding bias and effect modification?

Confounding: a third variable distorts the apparent exposure-outcome association (controlled by randomization, matching, stratification, multivariate analysis). Effect modification: the exposure's effect genuinely differs across levels of a third variable (a real finding, reported by stratum, not 'corrected').

List Erikson's psychosocial stages for the first three life stages and their core conflicts.

Infancy (0-1 yr): Trust vs. Mistrust. Toddler (1-3 yr): Autonomy vs. Shame and doubt. Preschool (3-6 yr): Initiative vs. Guilt.

What are the expected gross motor and language milestones at approximately 12 months of age?

~12 months: stands/takes first steps (walks), pincer grasp, says first words ('mama/dada' specific), and stranger anxiety; object permanence is established.

Distinguish the mature defense mechanisms (sublimation, altruism, suppression, humor) from immature ones.

Mature defenses are adaptive: sublimation (channeling impulses into socially acceptable acts), altruism, suppression (consciously postponing attention to a stressor), and humor. Immature defenses (e.g., projection, denial, displacement, regression, acting out, splitting) are maladaptive and associated with poorer functioning.

Define the defense mechanisms: projection, displacement, reaction formation, and isolation of affect.

Projection: attributing one's own unacceptable feelings to others. Displacement: redirecting emotions from the true target to a safer one. Reaction formation: replacing an unacceptable impulse with its opposite. Isolation of affect: separating feelings from events/ideas (describing trauma without emotion).

In behavioral theory, distinguish classical from operant conditioning, and positive vs negative reinforcement.

Classical conditioning: a neutral stimulus paired with an unconditioned stimulus elicits a conditioned response (Pavlov). Operant conditioning: behavior shaped by consequences (Skinner). Positive reinforcement = adding a reward to increase behavior; negative reinforcement = removing an aversive stimulus to increase behavior (both increase behavior).