STEP 1 Content Outline

General Principles

Biochemistry and molecular biology

• gene expression: DNA structure, replication, and exchange
  • DNA structure: single- and double-stranded DNA, stabilizing forces, supercoiling
  • analysis of DNA: sequencing, restriction analysis, PCR amplification, hybridization
  • DNA replication, mutation, repair, degradation, and inactivation
  • gene structure and organization; chromosomes; centromere, telomere
  • recombination, insertion sequences, transposons
  • mechanisms of genetic exchange, including transformation, transduction, conjugation, crossover, recombination, linkage
  • plasmids and bacteriophages
• gene expression: transcription, including defects
  • transcription of DNA into RNA, enzymatic reactions, RNA, RNA degradation
  • regulation: cis-regulatory elements, transcription factors, enhancers, promoters, silencers, repressants, splicing
• gene expression: translation, including defects
  • the genetic code
  • structure and function of tRNA
  • structure and function of ribosomes
  • protein synthesis
  • regulation of translation
  • post-translational modifications, including phosphorylation, addition of CHO units
  • protein degradation
• structure and function of proteins
  • principles of protein structure and folding
  • enzymes: kinetics, reaction mechanisms
  • structural and regulatory proteins: ligand binding, self-assembly
  • regulatory properties
• energy metabolism, including metabolic sequences and regulation
  • generation of energy from carbohydrates, fatty acids, and essential amino acids; glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, ketogenesis, electron transport and oxidative phosphorylation, glycogenolysis
  • storage of energy: gluconeogenesis, glycogenesis, fatty acid and triglyceride synthesis
  • thermodynamics: free energy, chemical equilibria and group transfer potential, energetics of ATP and other high-energy compounds
• metabolic pathways of small molecules and associated diseases
  • biosynthesis and degradation of amino acids (eg, homocystinuria, maple syrup urine disease)
  • biosynthesis and degradation of purine and pyrimidine nucleotides
  • biosynthesis and degradation of lipids (eg, dyslipidemias, carnitine deficiency, adrenogenital syndromes)
  • biosynthesis and degradation of porphyrins
  • galactosemia and other small sugar disorders
  • biosynthesis and degredation of alcohols and other small molecules
• biosynthesis and degradation of other macromolecules and associated abnormalities, complex carbohydrates (eg, lysosomal storage disease), glycoproteins, and proteoglycans (eg, type II glycogen storage disease)

Biology of cells

• structure and function of cell components (eg, nucleus, cytoskeleton, endoplasmic reticulum, plasma membrane)
• signal transduction (including basic principles, receptors and channels, second messengers, signal trasnduction pathways)
• cell-cell and cell-matrix adhesion
• cell motility
• intracellular sorting (eg, trafficking, endocytosis)
• cellular homeostasis (eg, turnover, pH maintenance, proteasome, ions, soluble proteins)
• cell cycle (eg, mitosis, meiosis, structure of spindle apparatus, cell cycle regulation)
• structure and function of basic tissue components (including epithelial cells, connective tissue cells, muscle cells, nerve cells, and extracellular matrix)
• adaptive cell response to injury
• intracellular accumulations (eg, pigments, fats, proteins, carbohydrates, minerals, inclusions, vacuoles)
• mechanisms of injury and necrosis
• apoptosis

Human development and genetics

• embryogenesis: programmed gene expression, tissue differentiation and morphogenesis, homeotic genes, and developmental regulation of gene expression
• congenital abnormalities: principles, patterns of anomalies, dysmorphogenesis
• principles of pedigree analysis, including inheritance patterns, occurrence and recurrence risk determination
• population genetics: Hardy-Weinberg law, founder effects, mutation-selection equilibrium
• genetic mechanisms: chromosomal abnormalities, mendelian inheritance, multifactorial diseases
• clinical genetics, including genetic testing, prenatal diagnosis, newborn screening, genetic counseling/ethics, gene therapy

Biology of tissue response to disease

• inflammation, including cells and mediators
  • acute inflammation and mediator systems
  • vascular response to injury, including mediators
  • inflammatory cell recruitment, including adherence and cell migration, and phagocytosis
  • bactericidal mechanisms and tissue injury
  • clinical manifestations (eg, pain, fever, leukocytosis, leukemoid reaction, and chills)
  • chronic inflammation
• reparative processes
  • wound healing, hemostasis, and repair: thrombosis, granulation tissue, angiogenesis, fibrosis, scar/keloid formation
  • regenerative processes
• neoplasia
  • classification, histologic diagnosis
  • grading and staging of neoplasms
  • cell biology, biochemistry, and molecular biology of neoplastic cells: transformation, oncogenes, altered cell differentiation, and proliferation
  • hereditary neoplastic disorders
  • invasion and metastasis
  • tumor immunology
  • paraneoplastic manifestations of cancer
  • cancer epidemiology and prevention

Gender, ethnic, and behavioral considerations affecting disease treatment and prevention, including psychosocial, cultural, occupational, and environmental

• progression through the life cycle, including birth through senescence
  • cognitive, language, motor skills, and social and interpersonal development
  • sexual development (eg, puberty, menopause)
  • influence of developmental stage on physician-patient interview
• psychologic and social factors influencing patient behavior
  • personality traits or coping style, including coping mechanisms
  • psychodynamic and behavioral factors, related past experience
  • family and cultural factors, including socioeconomic status, ethnicity, and gender
  • adaptive and maladaptive behavioral responses to stress and illness (eg, drug-seeking behavior, sleep deprivation)
  • interactions between the patient and the physician or the health care system (eg, transference)
  • patient adherence, including general and adolescent
• patient interviewing, consultation, and interactions with the family
  • establishing and maintaining rapport
  • data gathering
  • approaches to patient education
  • enticing patients to make lifestyle changes
  • communicating bad news
  • “difficult” interviews (eg, anxious or angry patients)
  • multicultural ethnic characteristics
• medical ethics, jurisprudence, and professional behavior
  • consent and informed consent to treatment
  • physician-patient relationships (eg, ethical conduct, confidentiality)
  • death and dying
  • birth-related issues
  • issues related to patient participation in research
  • interactions with other health professionals (eg, referral)
  • sexuality and the profession; other “boundary” issues
  • ethics of managed care
  • organization and cost of health care delivery

Multisystem processes

• nutrition
  • generation, expenditure, and storage of energy at the whole-body level
  • assessment of nutritional status across the life span, including calories, protein, essential nutrients, hypoalimentation
  • functions of nutrients, including essential, trans-fatty acids, cholesterol
  • protein-calorie malnutrition
  • vitamin deficiencies and/or toxicities
  • mineral deficiencies and toxicities
  • eating disorders (eg, obesity, anorexia, bulimia)
• temperature regulation
• adaptation to environmental extremes, including occupational exposures
  • physical and associated disorders (eg, temperature, radiation, burns, decreased atmospheric pressure, high-altitude sickness, increased water pressure)
  • chemical (eg, gases, vapors, smoke inhalation, agricultural hazards, volatile organic solvents, heavy metals, principles of poisoning and therapy)
• fluid, electrolyte, and acid-base balance and disorders (eg, dehydration, acidosis, alkalosis)

Pharmacodynamic and pharmacokinetic processes

• general principles
  • pharmacokinetics: absorption, distribution, metabolism, excretion, dosage intervals
  • mechanisms of drug action, structure-activity relationships
  • concentration- and dose-effect relationships (eg, efficacy, potency), types of agonists and antagonists and their actions
  • individual factors altering pharmacokinetics and pharmacodynamics (eg, age, gender, disease, tolerance, compliance, body weight, metabolic proficiency, pharmacogenetics)
  • drug side effects, overdosage, toxicology
  • drug interactions
  • regulatory issues (eg, drug development, approval, scheduling)
• general properties of autacoids, including peptides and analogs, biogenic amines, prostanoids and their inhibitors, and smooth muscle/endothelial autacoids
• general principles of autonomic pharmacology
• general properties of antimicrobials, including mechanisms of action and resistance
• general properties of antineoplastic agents and immunosuppressants, including drug effects on rapidly dividing mammalian cells

Microbial biology and infection

• microbial classification and its basis
• bacteria and bacterial diseases
  • structure and composition
  • metabolism, physiology, and regulation
  • genetics
  • nature and mechanisms of action of virulence factors
  • pathophysiology of infection
  • epidemiology and ecology
  • principles of cultivation, assay, and laboratory diagnosis
• viruses and viral diseases
  • physical and chemical properties
  • replication
  • genetics
  • principles of cultivation, assay, and laboratory diagnosis
  • molecular basis of pathogenesis
  • pathophysiology of infection
  • latent and persistent infections
  • epidemiology
  • oncogenic viruses
• fungi and fungal infections
  • structure, physiology, cultivation, and laboratory diagnosis
  • pathogenesis and epidemiology
• parasites and parasitic diseases
  • structure, physiology, and laboratory diagnosis
  • pathogenesis and epidemiology
• principles of sterilization and pure culture technique

Immune responses

• production and function of granulocytes, natural killer cells, and macrophages
• production and function of T lymphocytes, T-lymphocyte receptors
• production and function of B lymphocytes and plasma cells; immunoglobulin and antibodies: structure and biologic properties
• antigenicity and immunogenicity; antigen presentation; cell activation and regulation; tolerance and clonal deletion
• immunologic mediators: chemistry, function, molecular biology, classic and alternative complement pathways, cytokines, chemokines
• immunogenetics; MHC structure and function, class I, II molecules; erythrocyte antigens
• immunizations: vaccines, protective immunity
• alterations in immunologic function
  • T- or B-lymphocyte deficiencies (eg, DiGeorge syndrome)
  • deficiencies of phagocytic cells
  • combined immunodeficiency disease
  • HIV infection/AIDS and other acquired disorders of immune responsiveness
  • drug-induced alterations in immune responses, immunopharmacology
• immunologically mediated disorders
  • hypersensitivity (types I–IV)
  • transplant and transplant rejection
  • autoimmune disorders
  • risks of transplantation, transfusion (eg, graft-versus-host disease)
  • isoimmunization, hemolytic disease of the newborn
  • immunopathogenesis
• immunologic principles underlying diagnostic laboratory tests (eg, ELISA, complement fixation, RIA, agglutination)
• innate immunity

Quantitative methods

• fundamental concepts of measurement
  • scales of measurement
  • distribution, central tendency, variability, probability
  • disease prevalence and incidence
  • disease outcomes (eg, fatality rates)
  • associations (eg, correlation and covariance)
  • health impact (eg, risk differences and ratios)
  • sensitivity, specificity, predictive values
• fundamental concepts of study design
  • types of experimental studies (eg, clinical trials, community intervention trials)
  • types of observational studies (eg, cohort, case-control, cross-sectional, case series, community surveys)
  • sampling and sample size
  • subject selection and exposure allocation (eg, randomization, stratification, self-selection, systematic assignment)
  • outcome assessment
  • internal and external validity
• fundamental concepts of hypothesis testing and statistical inference
  • confidence intervals
  • statistical significance and Type I error
  • statistical power and Type II error