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

USMLE Step 1: Foundational & Basic Sciences syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for USMLE Step 1: Foundational & Basic Sciences in Medical Council Step exam for International Medical Graduates / ECFMG Certification, not a summary of it.

1. 1

   General Principles: Biochemistry, Genetics & Cell Biology

   3 topics

   • Molecular Biology & Genetics
     • DNA replication, transcription, translation
     • Mendelian and non-Mendelian inheritance patterns
     • Mutations, repair mechanisms, trinucleotide repeats
     • Population genetics and Hardy-Weinberg principle
   • Metabolism
     • Glycolysis, TCA cycle, oxidative phosphorylation
     • Glycogen storage and lipid metabolism disorders
     • Amino acid metabolism and urea cycle defects
     • Vitamin functions and deficiency syndromes
   • Cellular Biology & Signaling
     • Cell membrane transport and second messengers
     • Cytoskeleton, collagen, and connective tissue
     • Cell cycle regulation and apoptosis
2. 2

   General Pathology

   4 topics

   • Cellular Injury & Adaptation
     • Hypertrophy, hyperplasia, atrophy, metaplasia
     • Reversible vs irreversible injury, necrosis, apoptosis
     • Free radical injury and intracellular accumulations
   • Inflammation & Repair
     • Acute vs chronic inflammation mediators
     • Wound healing, granulation, and scar formation
     • Granulomatous inflammation
   • Neoplasia
     • Oncogenes, tumor suppressors, and carcinogenesis
     • Tumor grading, staging, and metastasis
     • Tumor markers and paraneoplastic syndromes
   • Hemodynamic disorders: edema, thrombosis, embolism, shock
3. 3

   Microbiology & Immunology

   4 topics

   • Bacteriology
     • Gram-positive and gram-negative pathogens
     • Bacterial toxins and virulence factors
     • Antibiotic mechanisms and resistance
   • Virology
     • DNA and RNA virus classification
     • Viral replication and host interaction
   • Mycology and parasitology essentials
   • Immunology
     • Innate vs adaptive immunity and complement
     • Hypersensitivity reactions types I-IV
     • Immunodeficiencies and autoimmunity
     • MHC, antigen presentation, and cytokines
4. 4

   General Pharmacology

   4 topics

   • Pharmacokinetics & Pharmacodynamics
     • Absorption, distribution, metabolism, excretion
     • Half-life, clearance, volume of distribution
     • Receptor binding, agonists, antagonists, efficacy
   • Autonomic nervous system pharmacology
   • Drug metabolism, CYP450 interactions, and toxicology
   • Adverse drug reactions and antidotes
5. 5

   Behavioral Sciences & Biostatistics

   3 topics

   • Epidemiology & Biostatistics
     • Study designs and bias
     • Sensitivity, specificity, predictive values
     • Hypothesis testing, p-values, confidence intervals
     • Relative risk, odds ratio, number needed to treat
   • Psychological development and aging
   • Defense mechanisms and behavioral theory

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

20 of 59 cards from the USMLE Step 1: Foundational & Basic Sciences deck — real questions with worked answers.

1. In molecular biology, what is the difference between a missense, nonsense, and silent point mutation?

   Missense = base change produces a different amino acid; Nonsense = base change produces a premature STOP codon (truncated protein); Silent = base change codes for the same amino acid (usually a wobble/3rd-position change).

2. What is the name and mechanism of the phenomenon where a single gene produces multiple distinct phenotypic effects?

   Pleiotropy — one gene influences several seemingly unrelated traits (e.g., PKU causing intellectual disability, hypopigmentation, and musty odor).

3. List the four phases of the eukaryotic cell cycle and the key checkpoint controlled by p53.

   G1 (growth), S (DNA synthesis), G2 (growth), M (mitosis). p53 controls the G1/S checkpoint, arresting cells with DNA damage; loss of p53 allows damaged cells to replicate (most commonly mutated tumor suppressor).

4. Which DNA repair mechanism is defective in xeroderma pigmentosum, and what is the clinical consequence?

   Nucleotide excision repair (removes bulky UV-induced pyrimidine dimers). Defect causes extreme UV sensitivity and dramatically increased skin cancer risk.

5. What is anticipation in genetics, and which class of disorders classically shows it?

   Anticipation = a disease becomes more severe and/or presents at an earlier age in successive generations; seen in trinucleotide (triplet) repeat expansion disorders (e.g., Huntington disease, fragile X, myotonic dystrophy).

6. Glycolysis: what is the net ATP, NADH, and pyruvate yield per glucose, and which is the rate-limiting enzyme?

   Net per glucose: 2 ATP, 2 NADH, 2 pyruvate. Rate-limiting enzyme is phosphofructokinase-1 (PFK-1), activated by AMP and fructose-2,6-bisphosphate, inhibited by ATP and citrate.

7. Which enzyme is the rate-limiting (committed) step of the TCA cycle, and how is it regulated?

   Isocitrate dehydrogenase. Activated by ADP and Ca2+; inhibited by ATP and NADH (high energy charge slows the cycle).

8. In oxidative phosphorylation, how many ATP are produced per NADH and per FADH2, and where do they enter the electron transport chain?

   ~2.5 ATP per NADH (enters at Complex I) and ~1.5 ATP per FADH2 (enters at Complex II). The difference reflects fewer protons pumped when starting at Complex II.

9. Which metabolic pathway generates NADPH and ribose-5-phosphate, and what is its rate-limiting enzyme?

   The pentose phosphate pathway (HMP shunt). Rate-limiting/committed enzyme is glucose-6-phosphate dehydrogenase (G6PD); NADPH is used for reductive synthesis and glutathione regeneration.

10. What are the three irreversible enzymes of glycolysis that must be bypassed in gluconeogenesis?

    Hexokinase/glucokinase, phosphofructokinase-1, and pyruvate kinase. Gluconeogenesis bypasses them with pyruvate carboxylase + PEP carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase.

11. Compare the second messengers and prototypical receptors for Gs, Gi, and Gq G-protein-coupled receptor pathways.

    Gs: activates adenylyl cyclase -> increased cAMP (e.g., beta-adrenergic). Gi: inhibits adenylyl cyclase -> decreased cAMP (e.g., M2, alpha-2). Gq: activates phospholipase C -> IP3 (Ca2+ release) + DAG (PKC) (e.g., alpha-1, M1, M3, H1).

12. What is the difference between receptor tyrosine kinase signaling and the JAK-STAT pathway?

    RTKs (e.g., insulin, EGF) autophosphorylate on ligand binding and activate RAS/MAPK and PI3K pathways. JAK-STAT (used by many cytokines/growth hormone/prolactin) relies on receptor-associated JAK kinases that phosphorylate STATs, which dimerize and act as transcription factors.

13. Name the three types of cellular adaptation to increased workload/stimulus and give the definition of each.

    Hyperplasia = increased cell number; Hypertrophy = increased cell size; Metaplasia = reversible change of one differentiated cell type to another (e.g., squamous to columnar in Barrett esophagus).

14. What distinguishes reversible from irreversible cell injury at the cellular level?

    Reversible: cellular swelling, ribosomal detachment, decreased ATP, membrane blebbing. Irreversible: mitochondrial damage (loss of ATP), severe membrane damage with Ca2+ influx, and leakage of enzymes; nuclear changes (pyknosis, karyorrhexis, karyolysis).

15. Compare the major morphologic patterns of necrosis: coagulative, liquefactive, caseous, fat, and fibrinoid.

    Coagulative: ischemia in most organs (preserved architecture, e.g., MI). Liquefactive: brain infarcts and abscesses (enzymatic digestion). Caseous: TB/fungal (cheese-like granuloma). Fat: pancreatitis/breast trauma (saponification). Fibrinoid: vascular wall damage in vasculitis/malignant hypertension.

16. Distinguish apoptosis from necrosis.

    Apoptosis: programmed, ATP-dependent, single-cell, intact membrane, no inflammation, apoptotic bodies. Necrosis: pathologic, ATP-depleted, groups of cells, membrane rupture with enzyme leakage, and inflammation.

17. What are the intrinsic and extrinsic pathways of apoptosis?

    Intrinsic (mitochondrial): triggered by injury/loss of survival signals -> Bax/Bak release cytochrome c -> activates caspase-9. Extrinsic (death receptor): Fas-FasL or TNF binding -> activates caspase-8. Both converge on executioner caspases-3/6/7.

18. List the five cardinal signs of acute inflammation and the Latin terms.

    Redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function (functio laesa).

19. What are the steps of leukocyte extravasation in acute inflammation, in order?

    1) Margination/rolling (selectins - E-selectin, P-selectin, Sialyl-Lewis X); 2) Tight adhesion (integrins binding ICAM-1/VCAM-1); 3) Diapedesis/transmigration (PECAM-1/CD31); 4) Chemotaxis/migration (C5a, LTB4, IL-8, bacterial products).

20. Compare a granuloma's caseating vs. non-caseating types and name a key cytokine for granuloma formation.

    Caseating granulomas (central necrosis) suggest TB or fungal infection; non-caseating granulomas occur in sarcoidosis, Crohn disease, berylliosis. Th1 cells secrete IFN-gamma, which (with TNF) activates macrophages/epithelioid cells; TNF is critical for maintenance.

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