General Principles + Foundations
12-16%of exam
Organ Systems + Pathology
60-75%of exam
Disciplines + Competencies
10-20%of exam
Quick Facts
- Exam
- USMLE Step 1
- Scoring
- Pass/Fail only
- Pass/Fail since
- Jan 26 2022
- Questions
- Up to 280
- Blocks
- 14 x 30 min
- Per block
- Up to 20
- Session
- 8-hour day
- Fee
- $695 (2026)
Tumor Markers
AFP=liver, CA-125=ovary, CEA=colon
Exotoxin vs Endotoxin
Exotoxin
- Secreted protein
- Highly toxic
- Toxoid vaccine
Endotoxin
- LPS, gram-negative
- Lysis released
- No toxoid
Secreted vs membrane
Biochem + Genetics
- Rate-limiting glycolysis
- PFK-1
- Tay-Sachs
- Hexosaminidase ANo HSM
- Gaucher
- GlucocerebrosidaseHSM
- PKU
- Phenylalanine hydroxylase
- Marfan
- Fibrillin-1 (FBN1)
- Anticipation
- Trinucleotide repeats
- Imprinting
- Prader-Willi / Angelman
- Mitochondrial
- Maternal inheritance
Collagen Types
Type I bone, II cartilage, III vessels, IV membrane
Microbiology Bugs
- Currant-jelly sputum
- Klebsiella
- Rusty sputum
- S. pneumoniae
- Rice-water stools
- Vibrio cholerae
- Bull's-eye rash
- Borrelia (Lyme)
- Sulfur granules
- Actinomyces
- Owl-eye inclusions
- CMV
- Negri bodies
- Rabies
- Tumbling motility
- Listeria
Antidote Recall
Acetaminophen=NAC; opioid=naloxone; benzo=flumazenil
Immunology
- Type I
- IgE, mast cells
- Type II
- Antibody, cell-bound
- Type III
- Immune complexes
- Type IV
- T-cell delayed
- MHC I
- CD8, all cells
- MHC II
- CD4, APCs
- Th1
- IFN-gamma, macrophages
- Th2
- IL-4/5, B cells
Pharm + Antidotes
- Acetaminophen
- N-acetylcysteine
- Opioids
- Naloxone
- Benzodiazepines
- Flumazenil
- Warfarin
- Vitamin K, FFP
- Heparin
- Protamine sulfate
- Organophosphates
- Atropine + pralidoxime
- Methanol/ethylene glycol
- Fomepizole
- Digoxin
- Digoxin Fab antibodies
High Anion Gap
MUDPILES
Transudate vs Exudate
Transudate
- Low protein
- Pressure-driven
- CHF, cirrhosis
Exudate
- High protein
- Inflammation-driven
- Infection, malignancy
Pressure vs inflammation
Anemia Workup
- Low MCV→Microcytic(Iron, thalassemia)
- Normal MCV→Normocytic
- High MCV→Macrocytic(B12, folate)
- High reticulocytes→Hemolytic / blood loss
- Low reticulocytes→Marrow failure
- Hypersegmented neutrophils→B12 or folate
- Neuro deficits→B12 deficiency(Not folate)
- Schistocytes present→Microangiopathic hemolysis
System Weights
- Repro + endocrine
- 12-16%
- Respiratory + renal
- 11-15%
- Behavioral + nervous
- 10-14%
- Blood + lymph/immune
- 9-13%
- MSK + skin
- 8-12%
- Multisystem
- 8-12%
- Cardiovascular
- 7-11%
- Gastrointestinal
- 6-10%
- Communication/social
- 6-9%
- Biostats/epidemiology
- 4-6%
Necrosis vs Apoptosis
Necrosis
- Cell swelling
- Membrane rupture
- Inflammation
Apoptosis
- Cell shrinkage
- Membrane intact
- No inflammation
Pathologic vs programmed
Acid-Base Picker
- Low pH, low HCO3→Metabolic acidosis
- High anion gap→MUDPILES causes
- Normal anion gap→Diarrhea / RTA
- Low pH, high CO2→Respiratory acidosis
- High pH, high HCO3→Metabolic alkalosis
- High pH, low CO2→Respiratory alkalosis
- Winter formula off→Mixed disorder
Cardio + Pulm + Renal
- Pulsus paradoxus
- Cardiac tamponade
- Boot-shaped heart
- Tetralogy of Fallot
- S3 gallop
- Heart failure
- Curschmann spirals
- Asthma
- Honeycomb lung
- Pulmonary fibrosis
- Kimmelstiel-Wilson
- Diabetic nephropathy
- RBC casts
- Glomerulonephritis
- Muddy-brown casts
- Acute tubular necrosis
Neuro + Endocrine
- Lewy bodies
- Parkinson disease
- Neurofibrillary tangles
- Alzheimer disease
- Negri-like, hyperphagia
- Kluver-Bucy
- Whorled psammoma bodies
- Meningioma
- Hurthle cells
- Hashimoto thyroiditis
- Orphan Annie nuclei
- Papillary thyroid cancer
- Pheochromocytoma
- Episodic hypertension
- Waterhouse-Friderichsen
- Adrenal hemorrhage
GI + Heme + MSK
- Anti-mitochondrial antibody
- Primary biliary cholangitis
- String sign
- Crohn disease
- Mallory bodies
- Alcoholic hepatitis
- Auer rods
- Acute myeloid leukemia
- Smudge cells
- CLL
- Reed-Sternberg cells
- Hodgkin lymphoma
- Bamboo spine
- Ankylosing spondylitis
- Anti-CCP
- Rheumatoid arthritis
2x2 Table
Sens/Spec down columns; PPV/NPV across rows
Pass vs Fail Report
Pass
- No numeric score
- No content feedback
- Single outcome
Fail
- Content areas given
- Distance from passing
- Guides retake
Pass quiet vs fail detailed
Discipline Picker
- Disease mechanism asked→Pathology(Highest yield)
- Normal function asked→Physiology
- Drug + side effect→Pharmacology
- Enzyme deficiency→Biochemistry
- Organism identification→Microbiology
- Antibody / hypersensitivity→Immunology
- Study design / stats→Biostatistics
- Patient counseling→Communication skills
Discipline Weights
- Pathology
- 45-55%Highest yield
- Physiology
- 30-40%
- Gross anatomy + embryo
- 10-20%
- Microbiology
- 10-20%
- Pharmacology
- 10-20%
- Behavioral sciences
- 10-15%
- Biochem + nutrition
- 5-15%
- Histology + cell biol
- 5-15%
- Immunology
- 5-15%
Sensitivity vs Specificity
Sensitivity
- True positive rate
- Screening test
- SnNout rules out
Specificity
- True negative rate
- Confirmatory test
- SpPin rules in
Screen vs confirm
Study Design Picker
- Exposure then outcome→Cohort study
- Outcome then exposure→Case-control study
- Snapshot prevalence→Cross-sectional study
- Random assignment→Randomized trial
- Pool many studies→Meta-analysis
Exam Logistics
- Items
- Up to 280
- Blocks
- 14 blocks
- Block time
- 30 minutes
- Per block
- Up to 20
- Break time
- 55 min minimum
- Tutorial
- 5-min optional
- Fee 2026
- $695
- Region fee
- +$205 outside US/Canada
Cohort vs Case-Control
Cohort
- Exposure first
- Relative risk
- Prospective common
Case-Control
- Outcome first
- Odds ratio
- Retrospective, rare disease
Forward vs backward
Biostatistics
- Sensitivity
- Rules out (SnNout)
- Specificity
- Rules in (SpPin)
- PPV
- Rises with prevalence
- NPV
- Falls with prevalence
- Relative risk
- Cohort studies
- Odds ratio
- Case-control studies
- Type I error
- False positive (alpha)
- Type II error
- False negative (beta)
Scoring Rules
- Outcome
- Pass or fail
- Numeric score
- Not reported
- Equivalent standard
- 196 prior scale
- Pass feedback
- No content feedback
- Fail feedback
- Content areas given
- Attempt cap
- 4 per Step
- Annual limit
- 3 per 12 months
- Result timing
- Usually 3-4 weeks
Common Traps
Score vs outcome
No 3-digit score ≠ Pass/fail only
Sensitivity vs specificity
Sens screens out ≠ Spec confirms in
RR vs OR
RR for cohort ≠ OR for case-control
Exotoxin vs endotoxin
Exotoxin secreted protein ≠ Endotoxin gram-negative LPS
B12 vs folate
B12 has neuro ≠ Folate no neuro
Necrosis vs apoptosis
Necrosis inflames ≠ Apoptosis silent
Step 1 vs MCAT
Step 1 licenses physicians ≠ MCAT is admissions
Last Minute
- 1.Pass/Fail only since 2022
- 2.No numeric score reported
- 3.14 blocks, 30 min each
- 4.Up to 280 items total
- 5.Pathology highest discipline weight
- 6.Sens screens; Spec confirms
- 7.RR cohort; OR case-control
- 8.B12 deficiency has neuro signs
- 9.Exotoxin protein; endotoxin LPS
- 10.Acetaminophen antidote is NAC
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