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.

Biology of Cells

  • Structure and function of cell components (e.g., nucleus, cytoskeleton, endoplasmic reticulum, plasma membrane)

  • Signal transduction (including basic principles, receptors and channels, second messengers, signal transduction pathways)

  • Cell adhesion and cell motility

  • Intracellular sorting (e.g., trafficking, endocytosis)

  • Cellular homeostasis (e.g., turnover, pH maintenance, proteasome, ions, soluble proteins)

  • Cell cycle (e.g., 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 (e.g., 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 (e.g., 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


  • 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

  • Par neoplastic manifestations of cancer

  • Cancer epidemiology and prevention

Multisystem processes


  • 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 (e.g., obesity, anorexia, bulimia)

Adaptation to environmental extremes, including occupational exposures

  • Physical and associated disorders (e.g., temperature, radiation, burns, decreased atmospheric pressure, high-altitude sickness, increased water pressure)

  • Chemical (e.g., gases, vapors, smoke inhalation, agricultural hazards, volatile organic solvents, heavy metals, principles of poisoning and therapy)

Pharmacodynamics and pharmacokinetic processes

General principles

  • Pharmacokinetics: absorption, distribution, metabolism, excretion, dosage intervals

  • Mechanisms of drug action, structure-activity relationships

  • Concentration- and dose-effect relationships (e.g., efficacy, potency), types of agonists and antagonists and their actions

  • Individual factors altering pharmacokinetics and pharmacodynamics (e.g., age, gender, disease, tolerance, compliance, body weight, metabolic proficiency, pharmacogenetics)

  • Drug side effects, overdosage, toxicology

  • Drug interactions

  • Regulatory issues (e.g., 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 immunosuppressant’s, 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

  • ntigenicity 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; transplantation Immunizations: vaccines, protective immunity

  • Immunologic principles underlying diagnostic laboratory tests (e.g., 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 (e.g., fatality rates)

  • Associations (e.g., correlation and covariance)

  • Health impact (e.g., risk differences and ratios)

  • Sensitivity, specificity, predictive values

Fundamental concepts of study design

  • Types of experimental studies (e.g., clinical trials, community intervention trials)

  • Types of observational studies (e.g., cohort, case-control, cross-sectional, case series, community surveys)

  • Sampling and sample size

  • Subject selection and exposure allocation (e.g., 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

  • Hematopoietic and Lymphoreticular Systems

Normal processes

Embryonic development, fetal maturation, and perinatal changes Organ structure and function

Repair, regeneration, and changes associated with stage of life

Cell/tissue structure and function

  • production and function of erythrocytes, hemoglobin, O2 and CO2 transport, transport proteins

  • production and function of leukocytes and the lymphoreticular system

  • production and function of platelets

  • production and function of coagulation and fibrinolytic factors

Abnormal processes

Infectious, Inflammatory, and Immunologic disorders

  • Infections of the blood, Reticuloendothelial system, and lymphatics

  • Allergic and anaphylactic reactions and other immunopathologic mechanisms

  • Acquired disorders of immune deficiency

  • Autoimmunity and autoimmune diseases (e.g., Coombs positive hemolytic anemia, pernicious anemia, cryoglobulinemias, ITP)

  • Anemia of chronic disease

  • Transfusion complications, transplant rejection

Traumatic and mechanical injury (e.g., mechanical injury to erythrocytes, splenic rupture)

Neoplastic disorders (e.g., lymphoma, leukemia, multiple myeloma)

Metabolic and regulatory disorders, including acquired and congenital

  • Anemias and cytopenias (e.g., iron deficiency anemia, hemoglobinopathies, hereditary spherocytosis)

  • Cythemia

  • Hemorrhagic and hemostatic disorders (e.g., coagulopathies, DIC)

  • Bleeding secondary to platelet disorders (e.g., von Willebrand)

Vascular and endothelial disorders (e.g., effects and complications of splenectomy, hypersplenism, TTP, hemolytic-uremic syndrome)

Systemic disorders affecting the hematopoietic and lymphoreticular system (e.g., nutritional deficiencies, systemic lupus erythematosus)

Idiopathic disorders

Principles of Therapeutics

Mechanisms of action, use, and adverse effects of drugs for treatment of disorders of the hematopoietic system

  • Blood and blood products

  • Treatment of anemia, drugs stimulating erythrocyte production (e.g., erythropoietin)

  • Drugs stimulating leukocyte production (e.g., G-CSF, GM-CSF)

  • Anticoagulants, thrombolytic drugs

  • Antiplatelet drugs

  • Antimicrobials (e.g., antimalarial, anti-HIV)

  • Antineoplastic and immunosuppressive drugs

  • Drugs used to treat acquired disorders of immune responsiveness

Other therapeutic modalities (e.g., splenectomy, chelating agents, radiation therapy for lymphomas, plasmapheresis)

Patterns Affecting Treatment

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

  • Emotional and behavioral factors (e.g., diet, depression and immune responses, "blood doping" among athletes)

  • Influence on person, family, and society (e.g., childhood leukemia)

  • Occupational and other environmental risk factors (e.g., heavy metals, hydrocarbons, lead)

  • Gender and ethnic factors (e.g., herbal treatments with bone marrow depression)

Progression through the life cycle, including birth through senescence

  • Cognitive, language, motor skills, and social and interpersonal development

  • Sexual development (e.g., puberty, menopause)

  • Influence of developmental stage on physician-patient interview