USMLE® Content Outline

Biochemistry and molecular biology

• Gene expression: DNA structure, replication, exchange, and epigenetics (eg, imprinting, Xactivation, DNA methylation)
• Gene expression: transcription
• Gene expression: translation, post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra-extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum
• Structure and function of proteins and enzymes (eg, enzyme kinetics and structural/regulatory proteins)
• Energy metabolism (eg, ATP generation, transport chain)

Biology of cells

• Adaptive cell responses and cellular homeostasis (eg, hypertrophy)
• Mechanisms of injury and necrosis, including pathologic processes (eg, liquefactive necrosis, free radical formation)
• Apoptosis
• Cell cycle and cell cycle regulation (eg, mitosis)
• Mechanisms of dysregulation
  • cell biology of cancer (eg, role of p53, proto-oncogenes)
  • general principles of invasion and metastasis, including cancer staging
• Cell/tissue structure, regulation, and function, including cytoskeleton, organelles, glycolipids, channels, gap junctions, extracellular matrix, and receptors

Human development and genetics

• Principles of pedigree analysis
  • inheritance patterns
  • occurrence and recurrence risk determination
• Population genetics: Hardy-Weinberg law, founder effects, mutation-selection equilibrium
• Principles of gene therapy
• Genetic testing and counseling
• Genetic mechanisms (eg, penetrance, genetic heterogeneity)

Biology of tissue response to disease

• Acute inflammatory responses (patterns of response)
  • acute inflammation and mediator systems (eg, histamine, prostaglandins, bradykinins, eosinophilic basic protein, nitric oxide)
  • vascular response to injury, including mediators principles of cell adherence and migration (eg, ECAMs, selectins, leukocytic diapedesis, and rolling)
  • microbicidal mechanisms and tissue injury (eg, defensins)
  • clinical manifestations (eg, pain, fever, leukocytosis, leukemoid reaction, chills)
• Chronic inflammatory responses (eg, tumor necrosis factor)
• Reparative processes wound healing, repair: thrombosis, granulation tissue, angiogenesis, fibrosis, scar/keloid formation regenerative process

Pharmacodynamic and pharmacokinetic processes: general principles

• Pharmacokinetics: absorption, distribution, metabolism, excretion, dosage intervals
• Mechanisms of drug action, structure-activity relationships (eg, anticancer drugs)
• Concentration and dose-effect relationships (eg, efficacy, potency), types of agonists (eg, full, partial, inverse) and antagonists and their actions
• Individual factors altering pharmacokinetics and pharmacodynamics (eg, age, gender, disease, tolerance, compliance, body weight, metabolic proficiency, pharmacogenetics)
• Mechanisms of drug adverse effects, overdosage, toxicology
• Mechanisms of drug interactions
• Signal transduction, including structure/function of all components of signal transduction pathways such as receptors, ligands (eg, general principles of nitric oxide, autocrine and paracrine signaling)

Microbial biology

• Microbial identification and classification, including principles, microorganism identification, and non-immunologic laboratory diagnosis
• Bacteria
  • structure (eg, cell walls, composition, appendages, virulence factors, extracellular products, toxins, mechanism of action of toxins)
  • processes, replication, and genetics (eg, metabolism, growth, and regulation)
  • oncogenesis
  • antibacterial agents (eg, mechanisms of action on organism, toxicity to humans, and mechanisms of resistance)
• Viruses
  • structure (eg, physical and chemical properties, virulence factors)
  • processes, replication, and genetics (eg, life cycles, location of virus in latent infection)
  • oncogenesis
  • antiviral agents (eg, mechanisms of action on virus, toxicity to humans, and mechanisms of resistance)
• Fungi
  • structure (eg, cell wall, composition, appendages, virulence factors, extracellular products, toxins, mechanisms of action of toxins)
  • processes, replication, and genetics (eg, asexual vs. sexual, metabolism, growth)
  • antifungal agents (eg, mechanisms of action on fungus, toxicity to humans, and mechanisms of resistance)
• Parasites
  • structure (eg, appendages, macroscopic features, and virulence factors)
  • processes, replication, and genetics (eg, life cycles, metabolism, and growth)
  • oncogenesis
  • antiparasitic agents (eg, mechanisms of action on parasite, toxicity to humans, and mechanisms of resistance)
• Prions

Normal age-related findings and care of the well patient

• Infancy and childhood (0-12 years)
  • Normal physical changes: linear growth, variations in linear growth, including constitutional delay; weight; head circumference; micturition, defecation, primary incontinence/bedwetting; normal physical examination; screening; sleep; teething syndrome
  • Developmental stages: motor; speech; cognitive; psychosocial; anticipatory guidance
  • Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, guns, swimming, motor vehicles, car seats); routine vaccinations
• Adolescence (13-17 years)
  • Normal physical changes: linear growth, variations in linear growth including constitutional delay; weight; puberty; normal physical examination; gynecomastia; autonomy/self-identity; sleep
  • Developmental stages: cognitive (eg, abstract thought); psychosocial (eg, autonomy, role confusion, sexual identity); anticipatory guidance
  • Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, risk-taking behavior, helmets, safe sex, motor vehicles, seat belts, distractions); routine vaccinations
• Adulthood (18-64 years)
  • Normal physical changes: weight; normal physical examination; screening; sleep
  • Developmental stages: cognitive; intimacy vs isolation; anticipatory guidance
  • Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention; routine vaccinations
• Older Adulthood (65 years and older)
  • Normal physical changes, including normal physical exam for age: weight, height (spinal compression), skin, bruising; normal physical examination; response to temperature; micturition, defecation; sleep
  • Developmental stages: motor; cognitive (eg, psychomotor slowing); psychosocial; integrity vs despair; retrospection; anticipatory guidance
  • Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, falls, general medical condition; polypharmacy, driving, caregiver stress); routine vaccinations

Normal processes

• Development of cells of the adaptive immune response, including positive and negative selection during immune development
• Structure, production, and function
  • granulocytes, natural killer cells, macrophages, mast cells, dendritic cells, cell receptors (eg, complement receptors and Toll-like receptors), cytokines, chemokines
  • T lymphocytes, including T-lymphocyte receptors, accessory molecules (eg, CD3, CD4, CD8, B7), cell activation and proliferation, cytotoxic T lymphocytes, and memory T lymphocytes
  • B lymphocytes and plasma cells, including B-lymphocyte receptors, immunoglobulins, cell activation and proliferation, including development of antibodies and memory B lymphocytes
  • host defense mechanisms, host barriers to infection, mucosal immunity (eg, gutassociated lymphoid tissue and bronchus-associated lymphoid tissue), anatomical locations of T and B lymphocytes
• Cellular basis of the immune response and immunologic mediators
  • antigen processing and presentation in the context of MHC I and MHC II molecules (eg, TAP, beta-2 microglobulin), intracellular pathways, mechanisms by which MHC is expressed on the surface; including distribution of MHC I and MHC II on different cells, mechanisms of MHC I and MHC II deficiencies, and the genetics of MHC
  • regulation of the adaptive immune response (eg, peripheral tolerance, anergy, regulatory T lymphocytes, termination of immune response, and B-T lymphocyte interactions)
  • activation, function, and molecular biology of complement (eg, anaphylatoxins) functional and molecular biology of cytokines (eg, IL 1-15)
• Basis of immunologic diagnostics (eg, antigen-antibody reactions used for diagnostic purposes, ELISA, immunoblotting, antigen-antibody changes over time, ABO typing)
• Principles of immunologic protection
  • vaccine production and mechanisms of vaccine action
    • biologically active antibodies (eg, monoclonal antibodies, polyclonal antibodies including IVIG, VZIG, rabies immunoglobulin)
• Effect of age on the function of components of the immune system

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Disorders associated with immunodeficiency
  • deficiency primarily of humoral immunity: common variable immunodeficiency; hyper IgM syndrome; hypogammaglobulinemia/agammaglobulinemia, X-linked (Bruton); selective immunodeficiency (eg, IgA, IgM, IgE)
  • deficiency/dysfunction primarily of cell-mediated immunity: adenosine deaminase deficiency; thymic aplasia (DiGeorge syndrome); severe combined immunodeficiency disease (SCID); Wiskott-Aldrich syndrome; granulomatosis; allergic reactions/skin
  • complement deficiency: alternative pathway component deficiency (C2, C3b, C3bB, C36B6); classical pathway component deficiency (C1q, C1r, C1-C5); terminal component deficiency (C5b-C9; terminal complement complex); C1 esterase inhibitor deficiency, hereditary angioedema; mannose-binding lectin (MBL) deficiency; membrane attack complex deficiency
  • deficiency of phagocytic cells and natural killer cells: Chediak-Higashi disease; chronic granulomatous disease and other disorders of phagocytosis; leukocyte adhesion deficiency
• HIV/AIDS: HIV1 and HIV2; AIDS; AIDS complications (eg, neuropathy, dementia, renal insufficiency); immunology of AIDS; immune reconstitution syndrome (IRS); secondary infections; noninfectious complications
• Immunologically mediated disorders
  • hypersensitivity reactions: type 1, 2, 3, including anaphylaxis; type 4; drug reactions; serum sickness
  • transplantation: rejection; graft-vs-host disease
• Adverse effects of drugs on the immune system: Jarisch-Herxheimer reaction; drugs affecting the immune system (eg, prednisone, azathioprine, cyclosporine, methotrexate, monoclonal antibody drugs [eg, abciximab, adalimumab; bevacizumab, infliximab, omalizumab, rituximab]); vaccine adverse effects

Normal Processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
• Cell/tissue structure and function
  • production and function of erythrocytes, including heme and hemoglobin synthesis; hemoglobin O2 and CO2 transport, transport proteins, erythropoietin production and function of platelets
  • production and function of coagulation and fibrinolytic factors; hemostasis
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious and immunologic
  • infectious disorders
    • bacteria
    • viral: hemorrhagic fever (Ebola virus, Marburg virus); chikungunya; dengue fever; Zika virus disease
    • primary infections of lymphoid tissue: lymphadenitis (viral, bacterial, fungal, parasitic); lymphangitis; buboes, bubonic plague (Yersinia pestis); cat scratch disease (Bartonella henselae)
    • immunologic and inflammatory disorders: cryoglobinemia, essential mixed cryoglobinemia; autoimmune hemolytic anemia; paroxysmal nocturnal hemoglobinuria; thrombotic thrombocytopenic purpura; hemolytic uremic syndrome
• Neoplasms: leukemia, acute (ALL, AML); leukemia, chronic (CLL, CML); lymphomas, Hodgkin disease, non-Hodgkin lymphoma, Burkitt lymphoma, T-cell lymphoma; multiple myeloma, dysproteinemias, monoclonal gammopathy of unknown significance (MGUS); myelofibrosis; myelodysplastic syndrome, myelodysplasias; other immunoproliferative neoplasms (eg, Waldenstrom macroglobulinemia)
• Anemia, cytopenias, and polycythemia anemias
  • decreased production: anemia of chronic disease
  • hemolysis: glucose-6-phosphate dehydrogenase deficiency; pyruvate kinase deficiency
  • disorders of hemoglobin, heme, or membrane: disorders of red cell membranes; hereditary spherocytosis, elliptocytosis; methemoglobinemia, congenital; sickle cell disease; sideroblastic anemia; thalassemias
  • other causes of anemia: blood loss, acute and chronic as a cause of anemia
  • cytopenias: aplastic anemia; leukopenia; neutropenia, cyclic neutropenia, agranulocytosis; pancytopenia; thrombocytopenia, quantitative; immune thrombocytopenic purpura (ITP)
  • cythemias: leukocytosis; polycythemia vera; secondary polycythemia
• Coagulation disorders (hypocoagulable and hypercoagulable conditions)
  • hypocoagulable: disseminated intravascular coagulation; hemophilia, congenital factor VIII [hemophilia A] and IX [hemophilia B]; hypofibrinogenemia; von Willebrand disease; platelet dysfunction, qualitative
  • hypercoagulable: heparin-induced thrombocytopenia; other coagulopathies (eg, homocysteinemia, hypoplasminogenemia, antithrombin III, protein C/protein S deficiency, Factor V Leiden, anticardiolipin antibodies, lupus anticoagulant, prothrombin G20210A mutation)
  • reactions to blood components: ABO incompatibility/anaphylaxis; Rh incompatibility/anaphylaxis; hemolysis, delayed; transfusion reaction; transfusion contaminated with bacteria; transfusion-related acute lung injury (TRALI); anaphylactoid reaction (IgA deficiency)
• Traumatic, mechanical, and vascular disorders: mechanical injury to erythrocytes (eg, cardiac valve hemolysis); disorders of the spleen; splenic rupture/laceration; splenic infarct; splenic abscess; effects/complications of splenectomy (eg, sepsis due to encapsulated bacteria); hypersplenism
• Adverse effects of drugs on the hematologic and lymphoreticular systems: antiplatelet drugs, antithrombin drugs (eg, dabigatran); chemotherapeutic agents; inhibitors of coagulation factors; methemoglobinemia, acquired; propylthiouracil; tumor lysis syndrome; warfarin

Normal Processes

• Psychodynamic and behavioral factors, related past experience (eg, transference, personality traits)
• Adaptive behavioral responses to stress and illness (eg, coping mechanisms)
• Maladaptive behavioral responses to stress and illness (eg, drug-seeking behavior, sleep deprivation)
• Patient adherence: general adherence; adolescent adherence

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Psychotic disorders: brief psychotic disorder; delusional disorder; psychotic disorder due to another medical condition; schizophrenia; schizoaffective disorder; substance-induced psychotic disorder
• Anxiety disorders: acute stress disorder; anxiety disorders (generalized anxiety disorder, anxiety due to another medical condition, social phobia); hyperventilation syndrome; obsessive-compulsive disorder; panic disorder with and without agoraphobia; phobic disorders; post-traumatic stress disorder; separation anxiety disorder; substance-induced anxiety disorder, trichotillomania
• Mood disorders: major depressive disorder with and without psychotic features, with and without seasonal pattern; major depressive disorder, postpartum, with and without psychotic features, including screening; cyclothymic disorder; persistent depressive disorder (dysthymia); bipolar disorder, manic/depressed/mixed; premenstrual dysphoric disorder; bipolar and related disorder or depressive disorder due to another medical condition; substance/medication-induced bipolar and related disorder or depressive disorder (illegal or prescribed); suicidal ideation/attempt
• Somatoform disorders: body dysmorphic disorder; conversion disorder, including psychogenic seizures; dissociative disorders; illness anxiety disorder (hypochondriasis); malingering; pain disorder; somatic symptom disorder
• Factitious disorders: factitious disorder imposed on self
• Eating disorders and impulse control disorders: anorexia nervosa; binge-eating disorder; bulimia nervosa; eating disorder; disruptive, impulse-control, and conduct disorders (eg, gambling, kleptomania, pyromania)
• Disorders originating in infancy/childhood: reactive attachment disorder; attentiondeficit/hyperactivity disorder; speech sound disorder or language disorder; learning disorder/dyslexia; intellectual developmental disorder and developmental delay, undefined, including school problems, fetal alcohol syndrome; oppositional defiant disorder, conduct disorder; autism spectrum disorder, Rett syndrome; psychoses with origin specific to childhood; elimination disorders (incontinence, encopresis); tic disorders/Tourette disorder
• Personality disorders: antisocial personality disorder; avoidant personality disorder; borderline personality disorder; dependent personality disorder; histrionic personality disorder; narcissistic personality disorder; obsessive-compulsive personality disorder; paranoid personality disorder; schizoid personality disorder
• Psychosocial disorders/behaviors: adjustment disorder; grief response/bereavement, normal and persistent complex; parent-child relational problems other than physical or emotional abuse; other psychosocial stress
• Sexual and gender identity disorders: gender dysphoria; psychosexual dysfunction
• Substance use disorders: alcohol use disorder/intoxication/dependence/withdrawal; tobacco/nicotine use disorder/dependence/withdrawal; varenicline use; cannabis use disorder/intoxication/dependence; hallucinogen use disorder/intoxication/dependence/withdrawal; inhalant use disorder/intoxication/dependence/withdrawal; opioid, heroin, including prescription drug, use disorder/intoxication/dependence/withdrawal; sedative, hypnotic, including benzodiazepine and barbiturate use disorder/intoxication/dependence/withdrawal; stimulant, cocaine, methamphetamine use disorder/intoxication/dependence/withdrawal; other drugs of use disorders (eg, ecstasy, PCP, bath salts)/intoxication/dependence/withdrawal; polysubstance use disorder/intoxication/dependence/withdrawal

Normal Processes

• Embryonic development, fetal maturation, and perinatal changes, including neural tube derivatives, cerebral ventricles, and neural crest derivatives
• Organ structure and function
  • spinal cord
    • gross anatomy and blood supply spinal reflexes
  • brain stem (eg, cranial nerves and nuclei, reticular formation, anatomy and blood supply, control of eye movements)
  • brain
    • gross anatomy and blood supply
    • higher function: cognition, language, memory, executive function
    • hypothalamic function
    • limbic system and emotional behavior
    • circadian rhythm sleep-wake disorder
  • sensory systems
    • general sensory modalities, including sharp, dull, temperature, vibratory, and proprioception
    • special sensory modalities, including vision, hearing, taste, olfaction, and balance
  • motor systems
    • brain and spinal cord (upper motoneuron)
    • basal ganglia and cerebellum
  • autonomic nervous system
  • peripheral nerves
• Cell/tissue structure and function, including neuronal cellular and molecular biology
  • axonal transport
  • excitable properties of neurons, axons, and dendrites, including channels
  • synthesis, storage, release, reuptake, and degradation of neurotransmitters and neuromodulators
  • presynaptic and postsynaptic receptor interactions, trophic and growth factors brain metabolism
  • glia, myelin brain homeostasis: blood-brain barrier, cerebrospinal fluid formation and flow, choroid plexus
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders: meningitis: bacterial (Actinomyces israelii; Haemophilus influenzae; Listeria monocytogenes; Mycobacterium tuberculosis; Neisseria meningitidis; Staphylococcus aureus, epidermidis; Streptococcus agalactiae; Streptococcus pneumoniae); viral (adenovirus, arboviruses, echovirus and coxsackie A & B viruses, polioviruses, herpes simplex virus, varicella zoster, human immunodeficiency virus, lymphocytic choriomeningitis virus, measles virus, mumps virus, St. Louis encephalitis virus, California encephalitis virus, Western equine encephalitis virus); fungal (Blastomycosis dermatitidis, Cryptococcus neoformans/gattii); spirochetal (Borrelia burgdorferi; Leptospira; Treponema pallidum, including neurosyphilis); protozoal/helminths (Acanthamoeba, Naegleria fowleri, Strongyloides stercoralis, Angiostrongylus cantonensis, Baylisascaris procyonis); encephalitis (herpesvirus [HSVI], varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, mumps virus, enterovirus, West Nile virus, St. Louis encephalitis virus, rabies virus, Eastern and Western equine encephalitis virus, poliovirus, Taenia, Toxoplasma gondii); prion disease (eg, Creutzfeldt-Jakob disease); botulism (Clostridium botulinum), tetanus (Clostridium tetani); CNS disorders associated with AIDS (eg, progressive multifocal leukoencephalopathy)
  • immunologic and inflammatory disorders: myasthenia gravis, including thymoma; multiple sclerosis; transverse myelitis
• Neoplasms (cerebral, spinal, and peripheral): benign (meningioma, neurofibromatosis); malignant (glioblastoma multiforme, astrocytoma, medulloblastoma, primary CNS lymphoma); metastatic (eg, breast, lung, pancreatic, testicular, melanoma)
• Cerebrovascular disease: arteriovenous malformations, ectatic cerebral vessels; transient ischemic attack; stroke, thrombotic: cerebral artery occlusion/cerebral infarction; stroke, embolic: cerebral embolism; stroke: intracerebral hemorrhage, including subarachnoid hemorrhage, traumatic intracranial hemorrhage; cerebral artery aneurysm; carotid artery stenosis/atherosclerosis/occlusion/dissection; vertebral artery deficiency/dissection; subclavian steal syndrome; vascular dementia; hypertensive encephalopathy; posterior reversible encephalopathy syndrome; venous sinus thrombosis
• Disorders relating to the spine, spinal cord, and spinal nerve roots: cauda equina syndrome; spinal artery thrombosis/embolus/infarct; spinal cord compression; spinal cord transection, paraplegia and quadriplegia, acute and chronic effects (eg, autonomic dysreflexia); spinal stenosis (cervical, lumbar); syringomyelia
• Cranial and peripheral nerve disorders
  • cranial nerve injury/disorders: cranial nerve injury; Bell palsy; anisocoria, miosis, mydriasis; internuclear ophthalmoplegia; nystagmus and other irregular eye movements; vestibular neuritis, labyrinthitis; ptosis of the eyelid; Horner syndrome
  • peripheral nerve/plexus injury/disorders: peripheral nerve injury, including brachial plexus; carpal/cubital/tarsal/peroneal tunnel syndrome; mononeuritis, Guillain-Barré syndrome; Miller Fisher syndrome; neuropathy (eg, Charcot-Marie-Tooth disease); herpes zoster
  • Neurologic pain syndromes: complex regional pain syndrome (reflex sympathetic dystrophy, causalgia); fibromyalgia; postherpetic neuralgia; phantom limb pain/syndrome; thalamic pain syndrome; trigeminal neuralgia
  • Degenerative disorders/amnestic syndromes: Alzheimer disease; frontotemporal dementia, including progressive supranuclear palsy, Lewy body disease; mild neurocognitive disorder, mild cognitive impairment
  • Global cerebral dysfunction: altered states of consciousness; delirium; coma/brain death
  • Neuromuscular disorders: amyotrophic lateral sclerosis/spinal muscular atrophy; muscular dystrophy (eg, Duchenne, myotonic); muscle channelopathies (eg, hypokalemic period paralysis)
  • Movement disorders: acute dystonia; adult tic disease; essential tremor; Huntington disease; Parkinson disease, including Parkinson dementia
  • Metabolic disorders: adrenoleukodystrophy; metabolic encephalopathy
  • Paroxysmal disorders: headache, including migraine, mixed, tension, ice-pick, cluster, medication withdrawal, caffeine withdrawal; seizure disorders, including generalized tonic-clonic, partial, absence, febrile
  • Sleep disorders: cataplexy and narcolepsy; circadian rhythm sleep-wake disorder; insomnia, primary; sleep terror disorder and sleepwalking; REM sleep behavior disorder; restless legs syndrome
  • Traumatic and mechanical disorders and disorders of increased intracranial pressure: anoxic brain damage, cerebral hypoxia; epidural, subdural hematoma (cerebral and spinal); intraparenchymal hemorrhage, traumatic subarachnoid hemorrhage; cerebral edema; pseudotumor cerebri (idiopathic intracranial hypertension); torticollis/cervical dystonia; hydrocephalus, including normal-pressure; traumatic brain injury (concussion)/postconcussion syndrome (dementia pugilistica); traumatic brain syndrome
  • Congenital disorders: Friedreich ataxia; neural tube defects (eg, spina bifida, holoprosencephaly, anencephaly); microcephaly; Sturge-Weber syndrome; tuberous sclerosis, von Hippel-Lindau disease; hydrocephalus, obstructive (Arnold-Chiari)
  • Adverse effects of drugs on the nervous system: acute dystonic reaction; drug-induced meningitis (eg, NSAIDs, sulfa drugs); drug-induced neuropathy (eg, vincristine, isoniazid, metronidazole); extrapyramidal adverse effects (eg, akathisia, dystonia, drug-induced parkinsonism); neuroleptic malignant syndrome; poisoning by psychotropic agents, including antidepressants; serotonin syndrome; tardive dyskinesia
  • Disorders of the eye and eyelid
    • infectious and inflammatory disorders of the eye: blepharitis/eyelid inflammation; chalazion; chorioretinitis; conjunctivitis (adenovirus)/keratoconjunctivitis; dacryocystitis; endophthalmitis; hordeolum; iridocyclitis; optic neuritis; periorbital cellulitis; uveitis
    • neoplasms of the eye: melanoma; retinoblastoma
    • disorders of the eye and eyelid, structural: cataract; glaucoma; lacrimal system disorders; pterygium; refractive disorders (presbyopia, myopia, hyperopia, astigmatism)
    • disorders of the pupil, iris, muscles (extraocular): amblyopia; strabismus
    • disorders of the retina: hypertensive retinopathy; macular degeneration; papilledema; retinal detachment; retinitis pigmentosa; vascular disorders affecting the retina, including central retinal artery embolus, retinal hemorrhage, amaurosis fugax, embolus, carotid artery stenosis, central retinal vein occlusion; visual impairment/blindness, night blindness
    • traumatic and mechanical disorders: black eye; burn of the eye and adnexa; corneal abrasion, ulcer; dislocated lens; foreign body in eye; hyphema; injury to optic nerve and pathways; laceration of the eye and eyelid; ocular open wounds; orbital fracture; subconjunctival hemorrhage
    • adverse effects of drugs on the eyes: ethambutol; hydroxychloroquine; prednisone
  • Disorders of the ear
    • infectious and inflammatory disorders of the ear: chondritis; mastoiditis; otitis, externa, media, interna, serous, suppurative, malignant otitis externa
    • neoplasms: acoustic neuroma, neurofibromatosis type 2; cholesteatoma
    • hearing loss/deafness: hearing loss, including noise-induced; otosclerosis; tinnitus
    • disorders of balance and spatial orientation: Meniere disease; motion sickness; vertigo, including benign positional vertigo
    • traumatic and mechanical disorders: barotrauma; foreign body in ear; impacted cerumen; laceration, avulsion; perforation of tympanic membrane; eustachian tube disorders
    • adverse effects of drugs on the ear: antineoplastic agents, including cisplatin; aminoglycosides; furosemide; salicylates

Normal Processes

• Embryonic development, fetal maturation, and neonatal changes
• Organ structure and function, including barrier function, thermal regulation
• Cell/tissue structure and function, eccrine function
• Repair, regeneration, and changes associated with stage of life (eg, senile purpura, male pattern baldness, postmenopausal hair changes)
• Skin defense mechanisms and normal flora

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders and infestations
    • bacterial: cellulitis, erysipelas, impetigo, staphylococcal scalded skin syndrome; abscess, cutaneous, including septic abscess; anthrax (Bacillus anthracis); carbuncle; folliculitis; pilonidal cyst, infected; pyoderma gangrenosum; MSSA and MRSA skin infections; mycobacterial infections (eg, leprosy, draining sinus); scarlet fever (group A Streptococcus)
    • viral: herpes simplex type 1 & type 2, herpes zoster, Ramsay-Hunt syndrome; molluscum contagiosum; hand-foot-and-mouth disease; herpangina; parvovirus; chickenpox, erythema infectiosum (fifth disease), rubella, measles, roseola (exanthema subitum); verrucae vulgaris
    • fungal (deep and superficial): candidiasis, skin; dermatophytosis, tinea corporis; dermatomycoses; diaper rash; onychomycosis
    • parasitic: cutaneous larva migrans; cutaneous leishmaniasis
    • infestations, nonvenomous bites, stings: scabies; lice; insect bites, including bed bugs
  • immunologic and inflammatory disorders
    • papulosquamous and eczematous dermatoses: psoriasis; lichen planus and lichenoid dermatoses; allergic/irritant contact dermatitis (eg, nickel); dermatoses caused by plants (poison ivy, poison oak)
    • vesiculobullous disorders: epidermolysis bullosa; dermatitis herpetiformis; pemphigus; pemphigoid
    • urticaria, erythema, exanthema, and purpura: erythema nodosum; atopic dermatitis; pityriasis rosea; urticaria; Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis
    • autoimmune disorders: vitiligo
• Neoplasms
  • benign neoplasms, cysts and other skin lesions: actinic keratoses; cysts, including epidermal; hemangiomas; lipoma; pigmented nevi; seborrheic keratosis; xanthomas
  • malignant neoplasms: basal cell carcinoma; squamous cell carcinoma; melanoma, including genital; Kaposi sarcoma; cutaneous T-cell lymphoma, mycosis fungoides
• Integumentary disorders (hair and hair follicles, nails, sweat glands, sebaceous glands, oral mucous membranes)
  • disorders of the hair and hair follicles: alopecia; seborrhea capitis/seborrheic dermatitis; tinea barbae and capitis
  • disorders of the nails (including ingrowing nail)
  • disorders of sweat and sebaceous glands: acne vulgaris; hidradenitis suppurativa; hyperhidrosis; ichthyosis; rosacea
• Oral disease: aphthous ulcers (stomatitis, canker sores); leukoplakia
• Disorders of pigmentation: albinism; lentigo
• Traumatic and mechanical disorders: animal bites (dogs, cats, etc); burns or wounds affecting the skin or subcutaneous tissue (eg, sunburn, other including blast injuries and burns); cauliflower ear; effects of ultraviolet light; keloids; tattoo; thermal injury, perniosis, frostbite; ulcers, decubitus
• Congenital disorders: xeroderma pigmentosum; benign lesions in neonates, infants, children (eg, congenital nevi)
• Adverse effects of drugs on skin and subcutaneous tissue: drug reactions, eruptions, including local reaction to vaccine

Normal processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
• Cell/tissue structure and function
  • biology of bones, joints, tendons, skeletal muscle, cartilage
  • exercise and physical conditioning/deconditioning
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, inflammatory, and immunologic disorders
  • infectious disorders: gangrene, dry and wet, clostridial myonecrosis (Clostridium perfringens); discitis; myositis, infective; necrotizing fasciitis; osteomyelitis; septic arthritis; spondylitis, tuberculous
  • immunologic disorders: ankylosing spondylitis; dermatomyositis/polymyositis; juvenile idiopathic arthritis; rheumatoid arthritis, Felty syndrome; psoriatic arthropathy
  • inflammatory disorders: adhesive capsulitis of shoulder (frozen shoulder syndrome); ankylosis/spondylopathy (inflammatory); bursitis; fasciitis; osteochondritis, osteochondritis dissecans; tendinitis, supraspinatus syndrome, enthesopathy of spine, elbow, ankle; temporomandibular joint disorders; fibrositis, myofascial pain syndrome; synovitis; tenosynovitis; myositis
• Neoplasms: benign neoplasms (e.g., ganglion cyst); malignant neoplasms of bone (eg, osteosarcoma, sarcoma, leiomyosarcoma, rhabdosarcoma); metastases to bone, secondary malignant neoplasm of bone
• Degenerative and metabolic disorders
  • degenerative/metabolic disorders of bone, tendon, and cartilage: chondromalacia; disc degeneration, herniated disc; Legg-Calvé-Perthes disease; Osgood-Schlatter disease; osteodystrophy; osteomalacia; osteonecrosis (avascular), bone infarct; osteoporosis; osteopenia; osteitis deformans (Paget disease of bone); pathologic fracture; radiculopathies; spondylolisthesis/spondylosis (degenerative)
  • degenerative/metabolic disorders of joints: gout, gouty arthritis, pseudogout; joint effusion; osteoarthritis
  • degenerative/metabolic disorders of muscles, ligaments, fascia: Dupuytren contracture; muscle calcification and ossification; muscle wasting and diffuse atrophy; rhabdomyolysis
• Traumatic and mechanical disorders: amputation and care of amputees; backache, including low back pain; blast injuries; compartment syndrome; contractures, hospital-acquired; contusions; dislocations; fractures; sprains, strains; kyphoscoliosis, scoliosis; rotator cuff syndrome; slipped capital femoral epiphysis; dislocation of hip
• Congenital disorders: achondroplasia/dwarfism; disorders of limb development (HOX gene mutation, phocomelia); developmental dysplasia of the hip; dislocation of hip in infantile spinal muscular atrophy; genu valgum or varum; foot deformities (flat foot, valgus/varus deformities); osteogenesis imperfecta; McArdle disease; mitochondrial myopathies
• Adverse effects of drugs on the musculoskeletal system: drug-induced myopathy (eg, steroids, statins, cocaine, AZT); malignant hyperthermia

Normal processes

• Embryonic development, fetal maturation, and perinatal transitional changes
• Organ structure and function
  • chambers, valves
  • cardiac cycle, mechanics, heart sounds, cardiac conduction
  • hemodynamics, including blood volume and systemic vascular resistance
  • circulation in specific vascular beds, including pulmonary and coronary
• Cell/tissue structure and function
  • heart muscle, metabolism, oxygen consumption, biochemistry, and secretory function (eg, atrial natriuretic peptide)
  • endothelium and secretory function, vascular smooth muscle, microcirculation, and lymph flow
  • neural and hormonal regulation of the heart, blood vessels, and blood volume, including responses to change in posture, exercise, and tissue metabolism, and autonomic responses
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders: bacterial endocarditis, myocarditis
  • immunologic and inflammatory disorders: atherosclerosis (eg, atherosclerosis of the aorta)
• Neoplasms: myxoma, metastases
• Dysrhythmias: premature beats (PACs, PVCs); atrial flutter/fibrillation; multifocal atrial tachycardia; paroxysmal tachycardias; ventricular tachycardia/fibrillation; wide complex tachycardia; torsades de pointes; bradycardias; atrioventricular block (first-, second-, third-degree); conduction disorder (LBBB, RBBB); cardiac arrest; sick sinus syndrome; prolonged QT syndrome; Wolff-Parkinson-White syndrome; carotid sinus hypersensitivity; pacemaker dysfunction, including failure to sense, capture
• Heart failure: chordae tendineae rupture; congestive heart failure; cor pulmonale; diastolic dysfunction; systolic dysfunction; mitral valve dysfunction; heart failure secondary to myocardial infarction; high-output heart failure, including thyrotoxicosis-induced, anemia-induced; tachycardia-induced; cardiogenic pulmonary edema
• Ischemic heart disease: acute coronary syndrome, acute myocardial infarction; angina pectoris, stable and unstable/coronary artery disease/coronary insufficiency; coronary artery spasm
• Diseases of the myocardium: cardiomyopathy, dilated, including alcoholic, viral, takotsubo; cardiomyopathy, obstructive hypertrophic; cardiomyopathy, familial dilated; cardiomyopathy, restrictive; hypertensive heart disease, left ventricular hypertrophy, right ventricular hypertrophy; complications of myocardial infarction; nontraumatic tamponade post-myocardial infarction; papillary muscle rupture/dysfunction; ventricular free wall rupture; myocarditis
• Diseases of the pericardium: chronic constrictive pericarditis; pericardial effusion; pericardial tamponade; acute pericarditis; pericarditis, following myocardial infarction, surgery, trauma Valvular heart disease: valve disorders, mitral/aortic/tricuspid, pulmonic (eg, regurgitation, stenosis, prolapse, insufficiency, vegetation); functional murmurs; rheumatic heart disease; complications of artificial valves
• Hypotension: orthostatic hypotension
• Hypertension: elevated blood pressure reading without diagnosis of hypertension; essential hypertension; malignant hypertension; secondary hypertension
• Dyslipidemia: hypercholesterolemia; hyperlipidemia; hypertriglyceridemia; lipoproteins/lipoprotein lipase deficiency
• Vascular disorders
  • disorders of the great vessels: aneurysm, aortic (abdominal/thoracic), dissection, ruptured; aneurysm, iliac, other peripheral vascular, ruptured; aortoiliac disease
  • peripheral arterial vascular disease: arterial embolus/thrombosis; arteriovenous fistula; atheroembolic disease; claudication; cholesterol emboli; hypertensive vascular disease; peripheral arterial disease; thromboangiitis obliterans
  • diseases of the veins: deep venous thrombosis, venous thromboembolism; phlebitis/thrombophlebitis; varicose veins; venous insufficiency; stasis ulcers, stasis dermatitis
• Traumatic and mechanical disorders: ventricular puncture; myocardial contusion; myocardial rupture; traumatic aortic dissection; traumatic tamponade
• Congenital disorders, including disease in adults: anomalous left coronary artery; atrial septal defect; coarctation of the aorta; endocardial cushion defect; patent foramen ovale; patent ductus arteriosus; tetralogy of Fallot; transposition of the great vessels; ventricular septal defect
• Adverse effects of drugs on the cardiovascular system: adriamycin; cocaine, amphetamine, PCP; ACE inhibitors, calcium channel blockers, alpha blockers, minoxidil

Normal processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
  • airways, including mechanics and regulation of breathing
  • lung parenchyma, including ventilation, perfusion, gas exchange
  • pleura
  • nasopharynx, sinuses
• Cell/tissue structure and function, including surfactant formation, and alveolar structure
• Repair, regeneration, and changes associated with stage of life
• Pulmonary defense mechanisms and normal flora

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious, immunologic, and inflammatory disorders of the upper airways: acute upper respiratory infection; viral infections (adenovirus, coronaviruses, coxsackievirus, influenza virus, parainfluenza virus, rhinoviruses); sinusitis; nasopharyngitis; epiglottitis; Bordetella pertussis pneumonia; croup; acute laryngitis; acute laryngotracheitis; tracheitis; pharyngitis; streptococcal throat infections; tonsillitis; peritonsillar abscess; rhinitis, allergic, chronic; ulcers of nasal cavity/sinuses
  • infectious, immunologic, and inflammatory disorders of the lower airways: hospitalacquired pneumonia; ventilator-associated pneumonia, community-acquired pneumonia, acute bronchiolitis; bronchiolitis obliterans with organizing pneumonia (BOOP); anthrax, pulmonary (Bacillus anthracis); aspiration pneumonia, pneumonitis; bronchitis, acute; bronchopneumonia; pneumonia (Burkholderia pseudomallei, Chlamydophila pneumoniae, Coxiella burnetii, Francisella tularensis, Haemophilus influenzae, Klebsiella pneumoniae, Legionella, Moraxella catarrhalis, Mycoplasma pneumoniae, Pseudomonas aeruginosa, Streptococcus, MSSA, MRSA, other gram‐negative bacteria); viral infection (eg, influenza A, B, adenovirus, H1N1, respiratory syncytial virus, parainfluenza virus); fungal infection (aspergillosis, including allergic bronchopulmonary aspergillosis and aspergilloma, histoplasmosis, coccidioidomycosis, Pneumocystis jirovecii); pulmonary tuberculosis; lung abscess; viral infection (eg, influenza A, B, adenovirus, respiratory syncytial virus, parainfluenza virus, avian influenza virus); fungal infection (aspergillosis, including allergic bronchopulmonary aspergillosis and aspergilloma, histoplasmosis, coccidioidomycosis, Pneumocystisjirovecii)
• Neoplasms
  • benign neoplasms: upper airways (eg, vocal cord polyps, nasal polyps, juvenile papillomatosis); lungs and pleura (eg, solitary pulmonary nodule, bronchial carcinoid tumors)
  • malignant neoplasms
    • upper airways: lip, oral cavity, and pharynx; head and neck cancer; larynx; trachea
    • lower airways and pleura: malignant neoplasms of bronchus and/or lung (squamous cell, adenocarcinoma, large cell, small cell); malignant neoplasms of pleura (mesothelioma); secondary malignant neoplasms of lung; secondary malignant neoplasms of pleura
  • metastatic neoplasms including pleural
• Obstructive airway disease: asthma, reactive airway disease; bronchiectasis; chronic airway obstruction; chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema
• Pneumoconiosis/fibrosing/restrictive pulmonary disorders/interstitial lung disease: pneumoconiosis; asbestosis; silicosis; silo-filler's lung, byssinosis, bagassosis, berylliosis; hypersensitivity pneumonitis; hypereosinophilic syndromes, Loeffler syndrome; interstitial pneumonia, usual (UIP), desquamative (DIP), nonspecific
• Respiratory failure/respiratory arrest and pulmonary vascular disorders: acute respiratory distress syndrome (ARDS); pulmonary hypertension; pulmonary vascular disorders, arteriovenous fistula; pulmonary edema, pulmonary cause and unspecified; pulmonary embolism; air and fat embolism; respiratory failure due to enteral feeding
• Metabolic, regulatory, and structural disorders: disorders of gas exchange; hypoventilation; hypoxia; pulmonary alveolar proteinosis; ventilation-perfusion imbalance
• Disorders of the pleura, mediastinum, and chest wall: chylothorax; costochondritis; empyema; hemothorax; mediastinitis; pleural effusion; pleuritis; pneumomediastinum; pneumothorax
• Traumatic and mechanical disorders
  • upper airways: epistaxis; barotrauma, sinus; laryngeal/pharyngeal obstruction; tracheoesophageal fistula; tracheal stenosis; tracheomalacia; trauma (eg, tracheal injury); foreign body (nose, pharynx, larynx, trachea); traumatic/mechanical disorders of the nasal cavity/sinuses (eg, septal perforation)
  • lower airways and pleura: atelectasis; diaphragm/chest wall injury; drowning and neardrowning; foreign body, upper and lower respiratory tract; penetrating chest wounds; pulmonary contusion; sleep apnea, obstructive and central; hypoventilation syndrome, obesity-hypoventilation syndrome
• Congenital disorders: bronchogenic cysts; congenital cysts; congenital diaphragmatic hernia; pulmonary sequestration; immotile cilia syndrome
• Adverse effects of drugs on the respiratory system: bleomycin, amiodarone; adverse effects of 100% oxygen; acute effects of tobacco/nicotine, inhalants, cocaine

Normal processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
  • anatomy of the alimentary canal, including mouth, pharynx, esophagus, stomach, small intestine, large intestine, anus, peritoneal cavity
  • liver and biliary system, including enterohepatic circulation
  • salivary glands and exocrine pancreas
  • gastrointestinal motility, including defecation digestion and absorption
• Cell/tissue structure and function
  • endocrine and neural regulatory functions, including GI hormones (eg, gastrin)
  • salivary, gastrointestinal, pancreatic, hepatic secretory products, including enzymes, proteins, bile salts, and processes
  • synthetic and metabolic functions of hepatocytes
• Repair, regeneration, and changes associated with stage of life
• Gastrointestinal defense mechanisms and normal flora

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders
    • bacterial: pseudomembranous colitis (Clostridium difficile); enteritis/enteric infections (includes gastroenteritis) (eg, Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, Yersinia enterocolitica, Campylobacter species, Vibrio cholerae, Salmonella species, Shigella species, traveler's/infectious diarrhea); hepatic abscess, subhepatic abscess, subphrenic abscess; peritonitis, primary and secondary; Whipple disease
    • viral: infectious esophagitis (eg, CMV, herpes); hepatitis A, B, C, D, E; coxsackievirus enteritis/colitis; Echovirus enteritis/colitis; rotavirus enteritis; mumps; gingivostomatitis, herpetic
    • fungal: thrush
    • parasitic: Cryptosporidium, Cyclospora, Entamoeba histolytica, Giardia, Isospora belli, Strongyloides stercoralis
  • immunologic and inflammatory disorders: autoimmune hepatitis; celiac disease; eosinophilic esophagitis; granulomatous enteritis; inflammatory bowel disease, including Crohn disease, regional enteritis, microscopic colitis (collagenous and lymphocytic colitis), ulcerative colitis, toxic megacolon
• Neoplasms
  • benign neoplasms, including polyps, cysts: stomach; small intestine; colon, rectum, and anus, including polyps
  • malignant neoplasms and pre-malignant conditions: oral cancer (eg, lips, mouth, tongue, salivary glands); esophageal, squamous and adenocarcinoma; Barrett esophagus; gastrinoma, Zollinger-Ellison syndrome; gastrointestinal carcinoid tumors; gastrointestinal stromal tumors; small intestine; stomach, adenocarcinoma, lymphoma, MALT; colon, rectum, anus; hereditary colon cancer syndromes, familial adenomatous polyposis (eg, Peutz-Jeghers syndrome, Gardner syndrome, Turcot syndrome,); MUTYH-associated polyposis; gallbladder, cholangiocarcinoma, adenocarcinoma of the ampulla of Vater; liver, including hepatoma; peritoneal cancer, including metastatic studding with cancer; pancreas
  • metastatic neoplasms
• Signs, symptoms, and ill-defined disorders: upper gastrointestinal bleeding; lower gastrointestinal bleeding; constipation; diarrhea; hematochezia; bright red rectal bleeding; melena; nausea, vomiting, rumination
• Disorders of the oral cavity, salivary glands, and esophagus
  • oral cavity and salivary glands: abscessed tooth; dental caries; malocclusion; disorders of the salivary glands (eg, stones, sialadenitis, parotitis)
  • esophagus: achalasia and cardiospasm; dysphagia; diverticulum (eg, Zenker); esophageal periapical abscess without sinus; esophagitis/esophageal reflux (GERD); esophagitis, pill; Mallory-Weiss syndrome; paraesophageal (hiatal) hernia; stricture and stenosis of esophagus
• Disorders of the stomach, small intestine, colon, rectum, anus
  • stomach: dyspepsia/hyperacidity; gastric ulcer; gastritis; peptic ulcer; peptic ulcer perforation; gastroparesis
  • small intestine, colon: appendicitis; angiodysplasia; diverticula, diverticulitis, diverticulosis; duodenitis, duodenal ulcer, peptic ulcer; gastroenteritis and colitis (noninfectious); granulomatous enterocolitis; Hirschsprung disease; impaction of intestine; intestinal obstruction/stricture; intussusception; irritable colon/irritable bowel syndrome; mesenteric ischemia/ischemic bowel/ischemic colitis; necrotizing enterocolitis; paralytic ileus; volvulus; malnutrition and malabsorption, including lactose intolerance, short bowel syndrome
  • rectum and anus: abscess of anal and rectal regions; anal fissure; anal fistula; ulcer; fecal incontinence; hemorrhage (rectum, anus); proctitis; hemorrhoids; rectal prolapse
• Disorders of the liver and biliary system, noninfectious
  • liver: cirrhosis; Dubin-Johnson, Rotor syndromes; end-stage liver disease, including indications for transplantation; Gilbert syndrome, Crigler-Najjar syndrome; hepatic coma/hepatic encephalopathy; hepatitis, noninfectious; hepatitis, fatty liver, alcoholic; hepatorenal syndrome; hepatopulmonary syndrome; jaundice; nonalcoholic fatty liver disease; portal hypertension/esophageal varices
  • biliary system: bile duct obstruction/cholestasis; cholangitis, including ascending; choledocholithiasis; cholelithiasis/cholecystitis; cholestasis due to parenteral nutrition; gallstone ileus; Mirizzi syndrome; primary biliary cirrhosis; primary sclerosing cholangitis
• Disorders of the pancreas: pancreatitis, acute; pancreatitis, chronic; pancreatitis, hereditary; pancreatic cyst/pseudocyst; pancreatic duct obstruction; pancreatic insufficiency
• Disorders of the peritoneal cavity: ascites
• Traumatic and mechanical disorders: abdominal wall defects; adhesions, postsurgical; digestive system complications of surgery; post-gastric surgery syndromes (eg, blind loop syndrome, adhesions); duodenal tear; foreign body in digestive system; inguinal, femoral, and abdominal wall hernias; open wound, abdominal; perforation of hollow viscus and blunt trauma; perforation/rupture of esophagus (Boerhaave syndrome); umbilical hernia
• Congenital disorders: annular pancreas, biliary atresia, cleft lip and palate, esophageal atresia, malrotation without volvulus, Meckel diverticulum, pyloric stenosis, tracheoesophageal fistula
• Adverse effects of drugs on the gastrointestinal system: drug-induced changes in motility (chronic laxative abuse, opioids); drug-induced gastritis, duodenitis, peptic ulcer disease (NSAIDs); drug-induced hepatitis (eg, acetaminophen, isoniazid); drug-induced pancreatitis (eg, thiazide diuretics)

Normal processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
  • kidneys, ureters, bladder, urethra
  • glomerular filtration and hemodynamics
  • urine concentration and dilution
  • renal mechanisms in acid-base balance
  • renal mechanisms in body fluid homeostasis
  • micturition
• Cell/tissue structure and function
  • renal metabolism and oxygen consumption
  • tubular reabsorption and secretion, including transport processes and proteins
  • hormones produced by or acting on the kidney (eg, renin, aldosterone, angiotensin II, vasopressin)
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders
    • upper urinary tract: granulomatous pyelonephritis; perinephric abscess; pyelonephritis; pyonephrosis; renal abscess; renal tuberculosis
    • lower urinary tract and urinary tract infections of unspecified location: cystitis; chlamydial and nonchlamydial
  • immunologic and inflammatory disorders
    • upper urinary tract
      • glomerular disorders: Alport syndrome; glomerular disease due to hepatitis B, C; glomerulonephritis, including poststreptococcal; IgA nephropathy; lupus nephritis; minimal change disease; nephrotic syndrome; thin basement membrane disease
      • tubular interstitial disease: acute tubular necrosis (ATN); acute interstitial nephritis; papillary necrosis; HIV nephropathy
    • lower urinary tract: interstitial cystitis
• Neoplasms
  • benign neoplasms and cysts: polycystic kidney disease
  • malignant neoplasms: renal (eg, Wilms tumor/nephroblastoma, renal cell carcinoma, renal tumors associated with congenital/hereditary conditions); urinary bladder and collecting system
• Signs, symptoms, and ill-defined disorders: dysuria; hematuria; oliguria, anuria; proteinuria
• Metabolic and regulatory disorders: acute kidney injury; renal insufficiency; azotemia, uremic syndrome; chronic kidney disease, including end-stage renal disease; cystinuria; Fanconi syndrome; hypertensive renal disease (renal complications of hypertension); renal calculi, ureteral calculi, nephrolithiasis; renal tubular acidosis
• Vascular disorders: renal artery stenosis (atherosclerosis, fibromuscular dysplasia, nephrosclerosis); renal vein thrombosis; renal infarction
• Traumatic and mechanical disorders: bladder rupture; neurogenic bladder; obstructive uropathy; posterior urethral valves; renal laceration; renal vascular injury; ureteral laceration/avulsion/disruption; urethral diverticulum; obstruction/stricture/prolapse, urethral/ureteral, vaginal walls, uterine, uterovaginal; urinary incontinence, including secondary enuresis; vesicoureteral reflux
• Congenital disorders: double ureters/ureteral duplication/double collecting system; horseshoe kidney; hydronephrosis/reflux; renal agenesis, renal hypoplasia, renal dysplasia; single kidney
• Adverse effects of drugs on the renal and urinary system: ACE inhibitors; aminoglycosides; amphotericin B; cisplatin; furosemide; gadolinium (nephrogenic systemic fibrosis); heroin; iodinated contrast dye; lithium; NSAIDs; penicillins; sulfa drugs; tenofovir; drug -induced urinary retention

Normal processes

• Organ structure and function: pregnancy, including fertilization, implantation, development of embryo, labor and delivery, the puerperium, lactation, gestational uterus, placenta

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Prenatal care
  • preconception counseling and care: folate deficiency prevention; immunizations; nutritional assessment, including vitamins; Rh screening
  • prenatal risk assessment/prevention: adolescent pregnancy; antepartum fetal evaluation, including biophysical profile; genetic screening; α-fetoprotein; diabetes mellitus; neural tube defects; Rh isoimmunization
  • supervision of normal pregnancy: assessment of gestational age; iron deficiency prevention; nutrition, including weight management; surveillance, including ultrasonography and assessment of fetal growth; vitamin deficiency prevention; infections, maternal, fetal, newborn (focus on prevention and screening): cytomegalovirus, coxsackievirus, hepatitis B virus, herpes simplex viruses, HIV, influenza virus, parvovirus B19 virus, rubella virus, varicella-zoster virus, Chlamydia trachomatis, Treponema pallidum, Streptococcus agalactiae, Toxoplasma gondii, amnionitis; asymptomatic urinary tract infection
• Obstetric complications: abortion, induced, septic, missed, spontaneous, threatened; acute fatty liver of pregnancy; anemia of pregnancy, sickle cell disease, thalassemia in pregnancy; antepartum hemorrhage, including third-trimester bleeding; cardiomyopathy of pregnancy; cervical insufficiency, cervical shortening; cholestasis of pregnancy, intrahepatic; congenital abnormalities, maternal (eg, bicornuate uterus); ectopic pregnancy; fetal abnormality affecting management of mother (eg, hydrocephalus, spina bifida); fetal growth restriction; gestational diabetes; maternal mortality; multiple gestation; placental abnormalities (abruptio placentae, placenta previa, premature separation of placenta); polyhydramnios, oligohydramnios; preeclampsia, eclampsia, HELLP syndrome, gestational hypertension; prolonged pregnancy; Rh isoimmunization affecting management of mother; vomiting in pregnancy (morning sickness, hyperemesis gravidarum); trauma in pregnancy; infections complicating pregnancy
• Labor and delivery: labor and delivery, uncomplicated; labor and delivery, complicated, including shoulder dystocia; cesarean delivery, including complications; cord compression, cord prolapse; fetal malpresentations (eg, breech/external cephalic); intrapartum fetal evaluation, including fetal heart tones; intrapartum prophylaxis (eg, HIV, Chlamydia, gonococcal prophylaxis); premature rupture of membranes; preterm (before 37 weeks' gestation) and postdates labor and delivery; threatened preterm labor
• Puerperium, including complications: lactation problems; breast-feeding problems; lochia; postpartum cardiomyopathy; postpartum blues; postpartum hemorrhage; postpartum sepsis; retained placenta, products of conception (eg, placenta accreta); uterine atony
• Newborn (birth to 4 weeks of age)
  • normal newborn
    • examination of liveborn at admission to hospital
    • screening, newborn
  • disorders of the newborn: screening, newborn; ABO incompatibility in newborn; hemolytic disease due to Rh incompatibility; birth asphyxia syndrome (liveborn neonate); birth trauma (eg, cord compression, brachial palsy, lacerations); drug withdrawal syndrome in newborn; feeding problems in newborn; fetal growth and development abnormalities, including fetal growth restriction; gastrointestinal obstruction; hypocalcemia of newborn; infections, congenital or peripartum (cytomegalovirus, herpes simplex viruses, HIV, hepatitis B, rubella virus, parvovirus B19 virus, varicella zoster virus, Chlamydia trachomatis, Streptococcus agalactiae, Treponema pallidum, Toxoplasma gondii); intrapartum fetal distress/death including stillborn; jaundice, fetal/neonatal/perinatal; laryngomalacia; macrosomia (large for gestational age); meconium aspiration syndrome; neonatal acne; neonatal Candida infection (thrush); neonatal hypoglycemia; neonatal conjunctivitis and dacryocystitis; ophthalmic gonorrhea; phenylketonuria; premature infant; postterm infant; pseudomembranous colitis of infancy; respiratory distress syndrome (hyaline membrane disease); respiratory problems after birth (eg, bronchopulmonary dysplasia, tracheomalacia; tracheoesophageal fistula in neonates); retinitis of prematurity; seizures in newborn; sudden infant death syndrome (SIDS), apparent life-threatening event (ALTE); tetanus neonatorum
• Congenital disorders, neonatal: congenital malformations and anomalies; neonatal hydrocele
• Adverse effects of drugs on pregnancy, childbirth, and the puerperium: alcohol, tobacco, and other drugs (ATOD); prenatal radiation exposure; teratology (eg, ACE inhibitors, SSRIs, warfarin, infections, toxins)
• Systemic disorders affecting pregnancy, labor and delivery, and puerperium: appendicitis; asthma; carpal tunnel syndrome in pregnancy; cirrhosis; deep venous thrombosis (DVT); diabetes mellitus; heart failure, valvular heart disease;hypertension; myasthenia gravis; obesity; pancreatitis; psychiatric disorders; renal calculus/calculi; renal failure/renal disease, including SLE; seizure disorders; thyroid disorders, hypothyroidism, hyperthyroidism

Normal processes

• Embryonic development, fetal maturation, and perinatal changes, gametogenesis
• Organ structure and function
  • female structure, including breast
  • female function (eg, ovulation, menstrual cycle, puberty)
  • intercourse, sexual response
• Cell/tissue structure and function: hypothalamic-pituitary-gonadal axis, sex steroids, and gestational hormones
• Reproductive system defense mechanisms and normal flora
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Breast
  • infectious, immunologic, and inflammatory disorders: breast abscess; inflammatory disease of breast, fat necrosis; mastitis; nipple discharge
  • neoplasms
    • benign and undefined neoplasms: breast cyst, solitary; fibrocystic changes; fibroadenoma; hypertrophy of breast; intraductal papilloma
    • malignant neoplasms (including screening): breast cancer; intraductal carcinoma; Paget disease of breast; phyllodes tumors
• Female reproductive system
  • infectious, immunologic, and inflammatory disorders: bacterial vaginosis; Bartholin gland abscess; cellulitis, pelvic; candidiasis of the vulva or vagina; lichen sclerosus; sexually transmitted infections and exposure; cervicitis and endocervicitis; chancroid (Haemophilus ducreyi); genital herpes; gonorrhea (Neisseria gonorrhoeae); human papillomavirus infection, genital/venereal/anal warts, condylomata acuminata; lymphogranuloma venereum (Chlamydia trachomatis), non-lymphogranuloma venereum; pelvic inflammatory disease; Fitz-Hugh-Curtis syndrome; salpingitis and oophoritis; syphilis (Treponema pallidum); trichomoniasis (Trichomonas vaginalis); urethritis; vaginitis; vulvovaginitis
• Neoplasms of the cervix, ovary, uterus, vagina, and vulva
  • benign neoplasms and cysts: abnormal Pap smear; benign neoplasm of ovary; endocervical and endometrial polyps; leiomyomata uteri; ovarian cyst
  • malignant and precancerous neoplasms: cervical cancer; HPV causing cancer; cervical dysplasia, HPV causing dysplasia; endometrial hyperplasia; endometrial/uterine cancer; gestational trophoblastic disease (hydatidiform mole); ovarian cancer; vulvar dysplasia and cancer
• Fertility and infertility: assisted reproductive techniques (ART); contraception (eg, oral contraceptives, IUD, vaginal cap, cervical sponge, diaphragm, implant, morning-after pill, male and female condoms); female infertility; gonadal dysgenesis 45,X (Turner syndrome); sterilization; tubal factors; infertility
• Menopause: ovarian failure, premature menopause; perimenopause; premenopausal menorrhagia; postmenopausal atrophic vaginitis (vaginal atrophy); postmenopausal bleeding; vasomotor symptoms
• Menstrual and endocrine disorders: abnormal uterine bleeding, including perimenopausal; absence of menstruation (primary amenorrhea, secondary amenorrhea including undiagnosed pregnancy); anovulation; dysmenorrhea; endometriosis; hirsutism, virilization; mittelschmerz; pelvic pain; polycystic ovarian syndrome; postcoital bleeding; premenstrual syndrome
• Sexual dysfunction: dyspareunia; orgasmic dysfunction; sexual desire/arousal syndrome; vaginismus
• Traumatic and mechanical disorders: Asherman syndrome; chronic inversion of uterus; chronic pelvic pain syndrome; cystocele; imperforate hymen; injuries, wounds, and burns affecting the female reproductive system and injuries, wounds, burns, and blast injuries; ovarian torsion; pelvic relaxation; rectocele; urethrocele
• Congenital disorders: müllerian agenesis; uterus didelphys, bicornuate uterus; short cervix
• Adverse effects of drugs on the female reproductive system and breast: antihistamines, H2-receptor blockers; benzodiazepines; beta-adrenergic blockers; hormone replacement; opioids; spironolactone; selective serotonin reuptake inhibitors; tricyclic antidepressants

Normal processes

• Embryonic development, fetal maturation, and neonatal changes, gametogenesis
• Organ structure and function
  • structure, male genitalia and prostate
  • function, male genitalia and prostate (eg, spermatogenesis, puberty)
  • intercourse, orgasm, erection
• Cell/tissue structure and function, including hypothalamic-pituitary-gonadal axis, sex steroids, and gestational hormones
• Reproductive system defense mechanisms and normal flora
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders: balanitis; epididymitis; orchitis; prostatitis; sexually transmitted infections and exposure; chancroid (Haemophilus ducreyi); genital herpes; gonorrhea (Neisseria gonorrhoeae); human papillomavirus infection, genital/venereal/anal warts, condylomata acuminata; lymphogranuloma venereum (Chlamydia trachomatis); syphilis (Treponema pallidum); trichomoniasis (Trichomonas vaginalis); urethritis, chlamydial and nonchlamydial, nongonococcal
  • immunologic and inflammatory disorders: autoimmune hypogonadism
• Neoplasms: malignant neoplasms, penile, prostate, testicular, breast
• Metabolic and regulatory disorders, including sexual dysfunction: erectile dysfunction, impotence; infertility, male factor; male sexual dysfunction; premature ejaculation
• Traumatic and mechanical disorders: benign prostatic hyperplasia/hypertrophy; circumcision, including complications; epididymal cyst; hydrocele; injuries, wounds, and burns to male genitalia, including blast injuries; penile laceration, penile fracture, Peyronie disease; phimosis; scrotal laceration; spermatocele; testicular rupture/avulsion/laceration; torsion of testis; urethral laceration/disruption; varicocele
• Congenital disorders of the male reproductive system: hypospadias; Klinefelter syndrome; undescended testicle
• Adverse effects of drugs on the male reproductive system: alcohol; androgens, testosterone; antipsychotics, antidepressants including selective serotonin reuptake inhibitors; betaadrenergic blockers; diuretic including thiazides; drug-induced priapism (eg, trazodone); finasteride, dutasteride; sildenafil, tadalafil, vardenafil; marijuana; nitric oxide reductase inhibitors

Normal processes

• Embryonic development, fetal maturation, and perinatal changes
• Organ structure and function
  • hypothalamus, posterior and anterior pituitary gland
  • thyroid gland
  • parathyroid gland
  • adrenal cortex, adrenal medulla
  • pancreatic islets
  • ovary and testis
  • adipose tissue
• Cell/tissue/structure and function, including hormone synthesis, secretion, action, metabolism
  • peptide hormones
  • steroid hormones, including vitamin D
  • thyroid hormones
  • catecholamine hormones
  • renin-angiotensin system
• Repair, regeneration, and changes associated with stage of life

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Diabetes mellitus and other disorders of the endocrine pancreas
  • diabetes mellitus: diabetes mellitus, type 1; diabetes mellitus, type 1.5; diabetes mellitus, type 2; diabetes mellitus, acute complications: hyperosmolar coma, hypoglycemic shock, ketoacidosis, including cerebral edema, associated electrolyte abnormalities; diabetes mellitus, chronic complications: gastrointestinal/gastroparesis, neurologic/neuropathy, ophthalmologic/retinopathy, peripheral vascular, renal/nephropathy, metabolic syndrome
  • hypoglycemia and islet cell disorders: hypoglycemia (secondary to insulinoma, surreptitious insulin use, sepsis, liver failure); hyperglycemia (secondary to glucagonoma); hyperinsulinism; islet cell tumors/insulinoma/somatostatinoma; pancreatic neuroendocrine tumors
• Thyroid disorders: cyst, nodule; euthyroid sick syndrome; goiter (euthyroid-normal thyroid function with goiter); hypothyroidism; hyperthyroidism, including thyrotoxicosis and thyroid storm; thyroiditis, including Hashimoto; Graves disease; neoplasms (benign cysts and nodules, thyroid cancer including papillary, follicular, medullary, and anaplastic); thyroid deficiency from pituitary disorder; infertility due to thyroid disease; secondary hypothyroidism and hyperthyroidism
• Parathyroid disorders: hyperparathyroidism; hypoparathyroidism; metabolic bone disease
• Adrenal disorders: corticoadrenal insufficiency (Addison disease); adrenal insufficiency, secondary; hypocortisolism; Cushing syndrome; hyperaldosteronism; neoplasms, benign and malignant (adrenal neuroblastoma, pheochromocytoma, adrenal carcinoma, adrenal adenoma, aldosteronoma, adrenal incidentaloma); delayed and precocious puberty; hypertensive endocrine disease
• Pituitary disorders: acromegaly/gigantism; diabetes insipidus; galactorrhea not associated with childbirth; panhypopituitarism from any cause; pituitary apoplexy (eg, Sheehan syndrome); growth hormone deficiency; short stature; SIADH (inappropriate secretion of ADH [vasopressin]); neoplasm, benign and malignant (pituitary adenomas, craniopharyngioma, metastatic disease); prolactinoma and hyperprolactinemia, including infertility due to these disorders; hypogonadism, primary and secondary
• Hypothalamic endocrine disorders
• Multiple endocrine neoplasia (MEN1, MEN2)
• Congenital disorders: disorders of sexual differentiation; congenital adrenal hyperplasia; androgen insensitivity/resistance syndrome; congenital hypothyroidism
• Adverse effects of drugs on the endocrine system: drug, medicinal, and biologic substance effects; exogenous steroid suppression of adrenal glands, anabolic steroids

Normal processes

• Principles of nutrition
  • generation, expenditure, and storage of energy at the whole-body level
  • functions of nutrients (eg, essential, trans-fatty acids, cholesterol)
• Electrolyte and water metabolism
  • electrolyte metabolism (calcium, potassium, phosphorus)
  • water metabolism
• Intracellular accumulations (eg, pigments, fats, proteins, carbohydrates, minerals, inclusions, vacuoles, lysosomal/glycogen storage disease and structures related to storage diseases, glycogen phosphorylase deficiency, Zellweger syndrome)

Abnormal Processes: Health and Health Maintenance, Screening, Diagnosis, Management, Risks, Prognosis

• Infectious, immunologic, and inflammatory disorders
  • infectious disorders
    • bacterial: brucellosis (Brucella spp); leptospirosis (Leptospira interrogans); Lyme disease (Borrelia burgdorferi); melioidosis (Burkholderia pseudomallei); miliary (disseminated) tuberculosis (Mycobacterium tuberculosis); tularemia (Francisella tularensis); toxic shock syndrome; Q fever (Coxiella burnetii); anaplasmosis and ehrlichiosis (Anaplasma and Ehrlichia species); rickettsiosis (Rocky Mountain spotted fever [Rickettsia rickettsii])
    • viral: infectious mononucleosis (Epstein-Barr virus); cytomegalovirus infection; yellow fever; human herpesvirus 8 (HHV-8)
    • fungal: blastomycosis (Blastomyces dermatitidis); candidiasis (Candida albicans); coccidioidomycosis (Coccidioides immitis/posadasii); histoplasmosis (Histoplasma capsulatum)
    • parasitic: schistosomiasis (Schistosoma); leishmaniasis (Leishmania spp), visceral (kalaazar); trypanosomiasis/Chagas disease, acute and chronic (Trypanosoma)
  • immunologic and inflammatory disorders: acute rheumatic fever; autoimmune arteritis/vasculitis; Behcet syndrome; Churg-Strauss syndrome; eosinophilic granuloma, histiocytosis, Langerhans cell histiocytosis; Goodpasture syndrome; Henoch-Schönlein purpura; Kawasaki disease; mixed connective tissue disease; polyangiitis; polyarteritis nodosa; polyglandular autoimmune syndrome, type 1; polymyalgia rheumatica, temporal arteritis; Raynaud disease/Raynaud syndrome; reactive arthritis, formerly Reiter disease, including Reiter arthritis; scleroderma (systemic sclerosis); Sjogren syndrome; systemic lupus erythematosus; Takayasu arteritis; granulomatosis with polyangiitis (formerly Wegener granulomatosis); familial Mediterranean fever; sarcoidosis, Lofgren syndrome
• Neoplasms and related disorders
  • paraneoplastic syndromes: endocrine (eg, SIADH, Cushing syndrome, hypercalcemia of malignancy [parathyroid‐related protein and paraneoplastic syndrome with hypercalcemia]); hematologic (polycythemia, nonbacterial thrombotic endocarditis); neurologic (myasthenic syndrome, paraneoplastic cerebellar degeneration, limbic encephalitis, pure sensory neuropathy, anti-NMDA receptor encephalitis); mucocutaneous (eg, acanthosis nigricans); musculoskeletal (eg, pulmonary osteoarthropathy, polymyositis); other (membranous glomerulonephritis)
  • inherited cancer syndromes: DNA repair abnormalities (eg, Fanconi anemia); hereditary nonpolyposis colorectal cancer (gastrointestinal and female reproductive)
• Signs, symptoms, and ill-defined disorders: arthralgias; abdominal pain; chest pain; cough; dizziness, light-headedness, syncope, including breath-holding spells with syncope; dyspnea, shortness of breath; edema, anasarca; fatigue; fever of unknown origin; hemoptysis; pain management (in a nonaddiction, nonpalliative-care setting); joint pain; lymphedema; palpitations; pruritus; unexpected weight gain/weight loss
• Nutrition
  • protein-calorie malnutrition (kwashiorkor, marasmus)
  • vitamin deficiencies and/or toxicities: vitamin A; vitamin B; vitamin B1, thiamine (eg, Wernicke- Korsakoff syndrome, beriberi); vitamin B3, niacin; vitamin B6, pyridoxine; vitamin B9, folic acid; vitamin B12, cobalamins (pernicious anemia); vitamin C (scurvy); vitamin D (rickets); vitamin E; vitamin K
  • mineral deficiencies and/or toxicities
  • obesity
  • enteral/parenteral nutrition (TPN)
• Toxins and environmental extremes
  • physical and associated disorders
    • temperature (eg, hypothermia, hyperthermia, heat stroke)
    • radiation (eg, radon, uranium mining, imaging studies)
    • thermal injury, burns, electrocution, lightning
    • decreased atmospheric pressure, high-altitude sickness
    • increased water pressure (nitrogen narcosis)
  • chemical including Gulf War illness
    • gases, vapors, smoke inhalation
    • agricultural hazards (eg, pesticides, green tobacco poisoning, anhydrous ammonia, Agent Orange)
    • olatile organic solvents
    • metals (eg, lead)
    • other chemical agents (eg, ethylene glycol, carbon tetrachloride, methanol; BPA)
    • principles of poisoning and therapy (eg, acetylsalicylic acid [ASA], acetaminophen)
• Venomous bites and stings: hymenoptera bites and stings; scorpion bites; snake bites; spider bites; jellyfish stings
• Fluid, electrolyte, and acid-base balance disorders
  • fluid volume and electrolyte/ion disorders: fluid volume disorders; dehydration; hypovolemia; volume overload; electrolyte disorders; hyponatremia, hypernatremia; hypokalemia, hyperkalemia; hypocalcemia, hypercalcemia; hypophosphatemia, hyperphosphatemia; hypomagnesemia
  • acid-base disorders: metabolic acidosis; metabolic alkalosis; respiratory acidosis; respiratory alkalosis; mixed acid-base disturbances
• Abuse
  • child, nonaccidental trauma/inflicted head trauma/factitious disorder by proxy
  • intimate partner abuse, sexual, emotional, and physical including injuries (eg, rib fractures) related to abuse
  • elder abuse, sexual, emotional, and physical including injuries (eg, rib fractures) related to abuse sexual assault
• Multiple trauma (eg, prioritization, blast injury involving more than one organ system)
• Shock, cardiogenic, hypovolemic, neurogenic, septic, sepsis, bacteremia, systemic inflammatory response syndrome (SIRS), refractory, multiorgan dysfunction syndrome: meningococcemia
• Genetic metabolic and developmental disorders
  • multifactorial: VATER syndrome, association syndromes
  • large genomic changes: Beckwith-Wiedemann syndrome; Down syndrome; PraderWilli syndrome
  • enzymatic/metabolic: alpha-1 antitrypsin deficiency; porphyria; inborn errors of metabolism (eg, maple syrup urine disease, diseases involving urea cycle); storage diseases (eg, Fabry disease, Tay-Sachs disease, glycogen storage disease, mucopolysaccharidoses)
  • structural protein disorders: amyloidosis; Ehlers-Danlos syndrome; immotile cilia syndrome (Kartagener syndrome; primary ciliary dyskinesia); Marfan syndrome
  • intracellular/extracellular transport receptors: cystic fibrosis; hemochromatosis; Wilson disease
  • triplet repeat/RNA disorders: fragile X syndrome
• Adverse effects of drugs on multisystem disorders: drug-induced electrolyte abnormalities and acid base-disorders (eg, albuterol; prednisone; diuretics; alcohol; drugs inducing polydipsia, SIADH, or diabetes insipidus)

• Epidemiology/population health
  • Measures of disease frequency: incidence/prevalence
  • Measures of health status: rates, crude and adjusted; reproductive rates (eg, maternal mortality, neonatal/infant/under-5 mortality); mortality, morbidity; standardization; life expectancy, health-adjusted life expectancy; population attributable risk (PAR), population attributable risk percent (PAR%); risk factors
  • Survival analysis interpretation (eg, Kaplan-Meier curve)
  • Composite health status indicators, measures of population impact: years of potential life lost; quality-adjusted life years; disability-adjusted life years; standardized mortality ratio
  • Population pyramids and impact of demographic changes
  • Disease surveillance and outbreak investigation: disease reporting; response to public health advisory, health promotion; recognition of clusters
  • Communicable disease transmission: attack rate; herd immunity; reportable diseases
  • Points of intervention: primary, secondary; community level (eg, cigarette taxes, soda taxes, smoke-free cities, buildings: restaurants, public buildings); school policies; access, healthy food, transportation, clean air, safe environments
• Study design, types and selection of studies (includes dependent/independent variables)
  • Descriptive studies (case report [one person]/case series [more than one])
  • Analytical studies: observational: community surveys; cross-sectional (individuals); ecological (populations); case control; retrospective and prospective cohort
  • Analytical studies: interventional: clinical trial (randomized controlled trial; double-blind; placebo-controlled; noninferiority/equivalence trials); community intervention
  • Systematic reviews and meta-analysis: potential uses; estimation of effect sizes; heterogeneity; publication bias; forest plots, funnel diagrams; risk of bias, bias risk scale
  • Obtaining and describing samples: matching, inclusion/exclusion criteria, selecting appropriate controls for studies, lack of controls, concealed allocation, randomization, stratification
  • Methods to handle noncompliance: loss to follow-up; intention-to-treat analysis
  • Qualitative analysis
• Measures of association
  • Relative risk
  • Odds ratio, hazard ratio
  • Other measures of association: number needed to treat/harm; absolute risk (AR), absolute risk percent (AR%); population attributable risk (PAR), population attributable risk percent (PAR%)
• Distributions of data: measures of central tendency; measures of variability; regression to mean; normal distribution; nominal measurement
• Correlation and regression, uses and interpretation: correlation coefficients; multiple regression
• Principles of testing and screening
  • Properties of a screening test: validity, accuracy, reliability; criteria for a screening test; confirmatory testing; appropriateness; lead-time bias, length bias; screening vs diagnostic tests
  • Sensitivity and specificity; predictive value, positive and negative
  • ROC curves
  • Probability: theory (independence, product, addition rules); decision trees; likelihood ratios (application of Bayes theorem); posttest, pretest
• Study interpretation, drawing conclusions from data
  • Causation: hypothesis-generating vs hypothesis-driven testing; causal criteria, temporality, temporal sequence, dose-response relationship; reverse causality
  • Chance
    • null hypothesis, Type I error and alpha level (multiple comparisons, random error/chance)
    • sample size and Type II error, beta, power
    • selection and interpretation of basic tests of statistical significance: chi-square; confidence intervals; p-values; t-test
    • a priori vs. post hoc analysis: subgroup analysis; error rate; affect types
  • Interpretation of graphs/tables and text
  • Bias, confounding, and threats to validity (includes methods to address)
    • selection, sampling bias
    • information bias: recall; ascertainment, ecologic fallacy, lack of blinding; loss to follow up
    • confounding variables, Hawthorne effect (includes methods to address)
    • other threats to validity (eg, placebo effect)
  • Internal vs. external validity: generalizability (external validity); efficacy vs effectiveness
  • Statistical vs. clinical significance; clinical and surrogate outcome/end point
• Clinical decision making, interpretation and use of evidence-based data and recommendations: application of study results to patient care and practice, including patient preferences and individualization of risk profiles; risk/benefit analysis; synthesis of concepts with real data
• Research ethics
  • Informed consent for research
  • Privacy of patient data (HIPAA)
  • Roles of institutional review boards (IRBs)
  • Intervention analysis: intervention analysis; stopping analysis; safety monitoring
  • Regulatory issues: drug development, phases of approval; appropriateness of placebo; appropriateness of randomized clinical trial; components of studies; ethics; scheduling; off-label use
• Other issues related to research ethics

• Communication and interpersonal skills, including health literacy and numeracy, cultural competence
  • Patient interviewing, consultation, and interactions with the family (patient-centered communication skills)
    • fostering the relationship (eg, expressing interest)
    • information gathering (eg, exploring patient's reaction to illness)
    • information provision (eg, providing information about working diagnosis)
    • making decisions (eg, eliciting patient's perspectives)
    • supporting emotions (eg, effective discussion with difficult patients)
    • enabling patient behaviors (eg, education and counseling)
  • Use of an interpreter or surrogate
• Medical ethics and jurisprudence, include issues related to death and dying and palliative care
  • Consent/informed consent to treatment, permission to treat (full disclosure, risks and benefits, placebos, alternative therapies, conflict of interest, and vulnerable populations)
  • Determination of medical decision-making capacity/informed refusal
  • Involuntary admission
  • Legal issues related to abuse (child, elder, and intimate partner)
    • child protective services, foster care, immunizations
    • legal requirements for reporting abuse or neglect/obligation to warn
  • Birth-related issues
  • Death and dying and palliative care
    • life support
    • advance directive, health care proxy, advance care planning
    • euthanasia and physician-assisted suicide
    • brain death/diagnosing brain death/diagnosing death
    • pronouncing death
    • organ donation
    • hospice
    • pain management, including ethical issues related to death and dying
    • information sharing, counseling families
    • psychosocial and spiritual counseling, fear and loneliness
  • Physician-patient relationship (boundaries, confidentiality including HIPAA, privacy, truthtelling, other principles of medical ethics, eg, autonomy, justice, beneficence)
  • Impaired physician, including duty to report impaired physician
  • Negligence/malpractice, including duty to report negligence and malpractice
  • Physician misconduct, including duty to report physician misconduct
  • Referrals
  • Cultural issues not otherwise coded
• Systems-based practice (including health systems, public health, community, schools) and patient safety (including basic concepts and terminology)
  • Complexity/systems thinking
    • Characteristics of a complex system and factors leading to complexity: how complexity leads to error
    • Health care/organizational behavior and culture: environmental factors, workplace design and process; staffing; overcommitment, space, people, time, scheduling; standardization, reducing variance, simplification, metrics; safety culture; integration of care across settings; overutilization of resources (imaging studies, antibiotics, opioids); economic factors
  • Quality improvement
    • Improvement science principles
      • Variation and standardization: variation in process, practice; checklists, guidelines, and clinical pathways
      • Reliability
    • Specific models of quality improvement: model for improvement: plan-do-study-act (PDSA), plan-do-check-act (PDCA)
    • Quality measurement
      • Structure, process, outcome, and balancing measures
      • Measurement tools: run and control charts
      • Development and application of system and individual quality measures: core measures; physician quality report system (PQRS); event reporting system
    • Strategies to improve quality
      • Role of leadership
      • Principles of change management in quality improvement: specific strategies
    • Attributes of high-quality health care
      • High-value/cost-conscious care: overutilization of resources, including diagnostic testing, medications
      • Equitable care: access
      • Patient-centered care
      • Timely care
  • Patient Safety
    • Patient safety principles
      • Epidemiology of medical error
      • Error categorization/definition: active vs latent errors; Swiss cheese model of error; preventable vs non-preventable; near miss events/safety hazards
      • Causes of error
        • Patient factors: understanding of medication use; health literacy; economic status; cultural factors (eg, religion); failure to make appointments; socioeconomic status
        • Physician factors: deficiency of knowledge; judgment errors; diagnostic errors; fatigue, sleep deprivation; bias – cognitive, availability, heuristic, anchoring, framing
        • Human factors (eg, cognitive, physical, environmental)
      • High reliability of organization (HRO) principles: change management and improvement science; conceptual models of improvement
      • Reporting and monitoring for errors: event reporting systems
      • Communication with patients after adverse events (disclosure/transparency)
    • Specific types of error
      • Transitions of care errors (eg, handoff communication including shift-to-shift, transfer, and discharge): handoffs and related communication; discontinuities; gaps; discharge; transfers
      • Medication errors
        • Ordering, transcribing, dispensing, administration (wrong quantity, wrong route,wrong drug)
        • Medication reconciliation
        • Mathematical error
      • Procedural errors
        • Universal protocol (time out); wrong patient; wrong site; wrong procedure
        • Retained foreign bodies
        • Injury to structures: paracentesis; bowel perforation; thoracentesis; pneumothorax; central venous/arterial line injuries; arterial puncture and bleeding and venous thrombosis; lumbar puncture bleeding; paralysis
        • Other errors: anesthesia-related errors; mathematical errors
      • Health care-associated infections: nosocomial infection – eg, surgical site, ventilator associated, catheter-related; handwashing procedures or inadequate number of handwashing stations; central line-associated blood stream infections; surgical site infections; catheter-associated urinary tract infections; ventilator-associated pneumonia
      • Documentation errors: electronic medical record (including voice-recognition software errors); record keeping; incorrect documentation (eg, wrong patient, wrong date, copying and pasting, pre-labeling)
      • Patient identification errors
        • Mislabeling: transfusion errors related to mislabeling
        • Verification/two identifiers: lack of dual validation, including verbal verification of lab results
      • Diagnostic errors: errors in diagnostic studies; misinterpretation
      • Monitoring errors
        • Cardiac monitoring/telemetry
        • Drug monitoring (warfarin, antibiotics)
      • Device-related errors
        • malfunction
        • programming error
        • incorrect use
    • Strategies to reduce error
      • Human factors engineering
        • Situational awareness
        • Hierarchy of effective interventions: forcing function; visual cues
      • Error analysis tools: error/near miss analysis; failure modes and effect analysis; morbidity and mortality review; root cause analysis
      • Safety behavior and culture at the individual level: hierarchy of health care, flattening hierarchy, speak up to power; afraid to report, fear; psychological safety; closed-loop communication
      • Teamwork: principles of highly effective teams; case management; physician teams, physician-physician communication; interprofessional/intraprofessional teams; strategies for communication among teams, including system-provider communication, physician-physician communication (eg, consultations), interprofessional communication, provider-patient communication
  • Health care policy and economics
    • Health care policy
      • Health care disparities: race/ethnicity; numeracy/literacy; socioeconomic status
      • Access to care: critical access systems or hospitals
      • Social justice
    • Health care economics/Health care financing
      • Types of insurance: Medicare, Medicaid, private insurance, self-pay
      • Navigating the insurance system: deductibles/co-pays; in-/out-of-network; preferred providers
      • Reimbursement issues affecting safety and quality: emergency services – EMTALA; pay-for-performance