USMLE Step 1 sample questions

Question 1

At a postnatal check-up, a 6-week-old girl weighs less than her birth weight. Her mother reports that she vomits and regurgitates bile-stained fluid after every feeding. An upper gastrointestinal contrast study shows the duodenojejunal junction located to the right of the midline and a corkscrew appearance of the proximal small bowel. Which of the following is the most likely diagnosis?

Accepted Answer

B. Intestinal malrotation with midgut volvulus. Bile-stained vomiting in an infant signals obstruction distal to the ampulla of Vater and is an emergency. A duodenojejunal junction displaced to the right of midline with a corkscrew configuration of the proximal small bowel indicates intestinal malrotation with midgut volvulus, in which the malpositioned bowel twists around the superior mesenteric vessels. Pyloric stenosis causes nonbilious vomiting because the obstruction is proximal to the ampulla.

Question 2

A 12-year-old girl is brought to the physician after her dentist found many unerupted and supernumerary teeth. Physical examination shows frontal bossing, a wide skull, and shoulders that she can bring together in front of her chest because of absent clavicles. Which of the following is the most likely diagnosis?

Accepted Answer

B. Cleidocranial dysplasia. Absent or hypoplastic clavicles that allow the shoulders to be approximated in the midline, together with delayed tooth eruption, supernumerary teeth, and frontal bossing, are characteristic of cleidocranial dysplasia. It is a disorder of membranous and endochondral bone formation associated with RUNX2 mutations. The clavicular and dental findings distinguish it from the other skeletal disorders.

Question 3

A 5-year-old boy who recently recovered from an upper respiratory tract infection develops scattered petechiae and easy bruising. He is otherwise well. Physical examination shows no hepatosplenomegaly or lymphadenopathy. Laboratory studies show a normal hemoglobin and leukocyte count with a platelet count of 18,000/mm3. A peripheral smear shows occasional large platelets and normal erythrocyte morphology. Which of the following is the most likely mechanism of the thrombocytopenia?

Accepted Answer

B. Immune-mediated destruction of platelets. Isolated thrombocytopenia with large platelets in an otherwise well child after a viral illness, with no organomegaly or other cytopenias, is immune thrombocytopenic purpura. Antiplatelet antibodies (often against GpIIb/IIIa) lead to splenic destruction of platelets, while the marrow compensates with increased megakaryocytes, producing the large platelets seen on smear. Consumptive microthrombi describe DIC or TTP, which would alter other lines; marrow replacement would cause additional cytopenias and abnormal cells.

Question 4

A 25-year-old woman and her husband, both of Southeast Asian descent, seek preconception counseling. Routine screening of the woman shows a mean corpuscular volume of 68 fL with a normal serum ferritin and a normal hemoglobin electrophoresis. Her husband has the same findings. Their offspring are at greatest risk for which of the following conditions?

Accepted Answer

B. Hemoglobin H disease or hydrops fetalis. Microcytosis with normal ferritin and a normal hemoglobin electrophoresis in a person of Southeast Asian descent suggests alpha-thalassemia trait. In Asian populations the cis deletion (both alpha genes deleted on the same chromosome) is common, so two carriers can produce offspring with only one or no functional alpha gene, causing hemoglobin H disease or hydrops fetalis (Hb Barts). A normal electrophoresis argues against beta-thalassemia (which raises HbA2) and against sickle cell disease.

Question 5

A 65-year-old man develops progressive gait unsteadiness over several months. On examination he has an intention tremor and dysmetria on finger-to-nose testing on the right side, and he tends to fall toward the right. There is no weakness or sensory loss. Damage to which of the following structures is the most likely cause?

Accepted Answer

B. Right cerebellar hemisphere. Lateral cerebellar hemisphere lesions cause ipsilateral limb dysmetria, intention tremor, and a tendency to fall toward the side of the lesion, because cerebellar output crosses twice and ultimately influences the same side of the body. Right-sided signs therefore localize to the right cerebellar hemisphere. The vermis controls truncal and gait stability rather than limb coordination, and internal capsule or frontal lesions would produce weakness or other deficits.

Question 6

A 26-year-old woman is brought to the emergency department after a motor vehicle collision. On examination she has loss of pain and temperature sensation on the left side of the body beginning a few segments below the level of injury, along with loss of motor function and of vibration and proprioception on the right side below the lesion. Which of the following best describes this pattern of injury?

Accepted Answer

C. Hemisection of the spinal cord (Brown-Séquard). Loss of pain and temperature contralateral to the lesion (spinothalamic tract, which crosses near the level of entry) combined with ipsilateral loss of motor function and of vibration/proprioception (corticospinal tract and dorsal columns, which cross higher up) is the hallmark of spinal cord hemisection, or Brown-Séquard syndrome. The dissociation between the side of pain/temperature loss and the side of motor and dorsal-column loss is what distinguishes it from the other listed syndromes.

Question 7

A 54-year-old woman comes to the physician because of a 1-week history of right shoulder pain that is worse when she lifts objects above her head and at night when she lies on the right side. There is no history of trauma. On examination there is tenderness over the lateral shoulder, a full passive range of motion, and pain and weakness on active abduction that is most pronounced during initiation of abduction. Which of the following muscles is most likely affected?

Accepted Answer

D. Supraspinatus. Pain with overhead activity, weakness on initiating abduction, and preserved passive motion point to a supraspinatus problem; the supraspinatus initiates the first roughly 15 degrees of abduction and is the most commonly injured rotator cuff muscle. The infraspinatus and teres minor produce external rotation, the subscapularis produces internal rotation, and the deltoid takes over abduction beyond the initial arc.

Question 8

A 65-year-old man who has worked outdoors as a farmer for decades comes to the physician because of skin lesions on his face, arms, and upper trunk that have been present for several years. Biopsy of one lesion shows actinic keratosis, and another shows squamous cell carcinoma. Which of the following is the most likely mechanism responsible for the development of the squamous cell carcinoma?

Accepted Answer

B. Formation of pyrimidine dimers from ultraviolet radiation. Chronic ultraviolet exposure induces formation of pyrimidine dimers in DNA. These distort the helix and, if not repaired by nucleotide excision repair, lead to mutations that drive actinic keratoses and squamous cell carcinoma. The farmer's long history of sun exposure fits this mechanism. The other options do not account for the UV-driven mutagenesis underlying these lesions.

Question 9

A 24-year-old man is referred for evaluation of a heart murmur found on a routine examination. He is asymptomatic. On auscultation there is a fixed splitting of the second heart sound that does not vary with respiration, along with a soft mid-systolic murmur at the left upper sternal border and a soft mid-diastolic rumble at the lower left sternal border. There is a right ventricular heave. Which of the following is the most likely diagnosis?

Accepted Answer

B. Atrial septal defect. Wide, fixed splitting of S2 that does not change with respiration is the classic sign of an atrial septal defect, because the left-to-right shunt keeps right-sided volume and pulmonary flow elevated throughout the respiratory cycle. The increased flow produces a pulmonic mid-systolic murmur and, when large, a tricuspid diastolic rumble. Aortic and pulmonic stenosis cause ejection murmurs without fixed splitting; mitral stenosis gives a loud S1 with an opening snap; mitral valve prolapse gives a mid-systolic click.

Question 10

A 39-year-old man comes to the physician for a routine examination. He is asymptomatic and has no family history of sudden death. A grade 3/6 systolic murmur is heard at the left lower sternal border. The murmur becomes louder when he stands up from a squatting position and softer when he squeezes his fists firmly. An echocardiogram shows asymmetric septal hypertrophy with systolic anterior motion of the mitral valve. A mutation in a gene encoding which of the following proteins is the most likely cause?

Accepted Answer

A. Beta-myosin heavy chain. The findings describe hypertrophic cardiomyopathy: a murmur that increases with reduced preload (standing) and decreases with increased afterload (handgrip), plus asymmetric septal hypertrophy and systolic anterior motion of the mitral valve. It is most commonly caused by autosomal dominant mutations in sarcomere genes, most often beta-myosin heavy chain (MYH7) and myosin-binding protein C. Dystrophin mutations cause muscular dystrophies, fibrillin-1 causes Marfan syndrome, and transthyretin causes an infiltrative restrictive cardiomyopathy.

Question 11

A 70-year-old man with longstanding congestive heart failure has had decreasing urine output and fatigue over 2 days. He stopped taking his medications a week ago. His blood pressure is 120/80 mm Hg. Laboratory studies show a serum urea nitrogen of 40 mg/dL and creatinine of 2.0 mg/dL (ratio 20:1), a urine sodium of 5 mEq/L, and a urine specific gravity of 1.025. Which of the following best explains these findings?

Accepted Answer

D. Prerenal azotemia from decreased renal perfusion. A high BUN-to-creatinine ratio (about 20:1), a very low urine sodium, and concentrated urine indicate prerenal azotemia. Reduced cardiac output lowers renal blood flow, so the kidney avidly reabsorbs sodium and water and reabsorbs urea along with it. The tubules are intact, distinguishing this from acute tubular necrosis, in which urine sodium is high and the urine is isosthenuric. Interstitial nephritis, obstruction, and glomerulonephritis give different urinary findings.

Question 12

A 15-year-old boy with nasal polyps develops bronchospasm and facial flushing within 30 minutes of taking a medication for a headache. The drug he took inhibits cyclooxygenase. Increased production of which of the following mediators best explains his bronchospasm?

Accepted Answer

C. Leukotrienes C4, D4, and E4. This is aspirin-exacerbated respiratory disease (the triad of asthma, nasal polyps, and NSAID sensitivity). Blocking cyclooxygenase shunts arachidonic acid down the 5-lipoxygenase pathway, increasing production of the cysteinyl leukotrienes C4, D4, and E4, which cause bronchoconstriction and increased bronchial tone. The reaction is pharmacologic rather than IgE-mediated, so it is not true allergy and does not depend on prior sensitization.

Question 13

A 45-year-old woman comes to the emergency department because of a 1-day history of fever and constant right upper quadrant abdominal pain. She has had several previous episodes of similar pain after eating fatty meals that resolved on their own. Her temperature is 38.4°C (101.1°F). When the examiner presses on the right upper quadrant and asks her to take a deep breath, she stops inspiration abruptly because of pain. Which of the following physical examination findings is being described?

Accepted Answer

C. Murphy sign. Arrest of inspiration during deep palpation of the right upper quadrant is a positive Murphy sign, seen in acute cholecystitis when the inflamed gallbladder descends and contacts the examiner's hand. The history of recurrent post-fatty-meal pain reflects biliary colic from gallstones. Cullen sign is periumbilical bruising; McBurney point tenderness and the psoas and Rovsing signs point to appendicitis.

Question 14

A newborn boy delivered at 39 weeks' gestation develops bilious vomiting and abdominal distention within the first day of life. The pregnancy was complicated by polyhydramnios. An abdominal radiograph shows two large gas-filled structures in the upper abdomen with no gas distal to them. The infant also has upslanting palpebral fissures and a single transverse palmar crease. Failure of which of the following embryologic processes best explains the intestinal finding?

Accepted Answer

B. Recanalization of the duodenum. The double-bubble sign with absent distal gas, bilious vomiting, polyhydramnios, and features of Down syndrome indicate duodenal atresia. During development the duodenal lumen is transiently obliterated by proliferating epithelium and must recanalize; failure of recanalization produces atresia. Midgut rotation defects cause malrotation/volvulus, vitelline duct failure causes Meckel diverticulum, and failed neural crest migration causes Hirschsprung disease.

Question 15

A 22-year-old woman at 12 weeks' gestation by dates comes to the physician because of vaginal bleeding. Her uterus is larger than expected for gestational age. Serum beta-hCG is markedly elevated. Pelvic ultrasonography shows a heterogeneous intrauterine mass with multiple small cystic spaces and no identifiable fetus or fetal heart activity. Which of the following best describes the underlying abnormality?

Accepted Answer

A. Fertilization of an empty ovum by sperm with subsequent duplication of paternal DNA. The snowstorm/cystic intrauterine mass with very high beta-hCG, a uterus large for dates, and no fetus is a complete hydatidiform mole. It typically arises when an empty ovum is fertilized and the genome is entirely paternal (often 46,XX from duplication of a single sperm), so no fetal tissue forms. A partial mole is triploid with fetal parts; ectopic pregnancy implants outside the uterus; choriocarcinoma is the malignant trophoblastic tumor that can follow a mole.

Question 16

A newborn with ambiguous external genitalia is evaluated. Chromosomal analysis shows a 46,XX karyotype. The infant is found to have virilized external genitalia, and serum studies show elevated 17-hydroxyprogesterone. Serum sodium is low and potassium is high. A deficiency of which of the following enzymes is the most likely cause?

Accepted Answer

D. 21-hydroxylase. A virilized 46,XX newborn with elevated 17-hydroxyprogesterone and salt wasting (low sodium, high potassium) is the classic presentation of 21-hydroxylase deficiency, the most common congenital adrenal hyperplasia. Loss of the enzyme blocks cortisol and aldosterone synthesis and shunts precursors into androgens. 11-beta-hydroxylase deficiency causes virilization but with hypertension (elevated 11-deoxycorticosterone); 17-alpha-hydroxylase deficiency causes hypertension without virilization; 5-alpha-reductase deficiency affects 46,XY infants.

Question 17

A 65-year-old man with diabetic ketoacidosis develops fever and proptosis of the left eye over 3 days. He is unable to move the left eye fully. Examination shows a black, necrotic eschar on the nasal mucosa. A biopsy of the affected tissue is most likely to show which of the following organisms?

Accepted Answer

A. Broad, ribbon-like hyphae with wide-angle branching. Rhinocerebral mucormycosis occurs in poorly controlled diabetics, particularly during ketoacidosis, and presents with facial pain, proptosis, cranial nerve involvement, and a black necrotic eschar from angioinvasion. The causative Mucorales fungi show broad, nonseptate, ribbon-like hyphae that branch at wide (roughly 90-degree) angles. Acute-angle septate hyphae describe Aspergillus, the thick capsule describes Cryptococcus, pseudohyphae describe Candida, and spherules describe Coccidioides.

Question 18

A first-year medical student is studying how integral membrane proteins remain anchored within the lipid bilayer. Which of the following best explains the mechanism that holds an integral membrane protein within the membrane?

Accepted Answer

C. Hydrophobic interactions between nonpolar amino acid side chains and the fatty acyl tails of the bilayer. Integral membrane proteins span the hydrophobic core of the bilayer, where their membrane-embedded segments are rich in nonpolar amino acids. These nonpolar side chains interact with the fatty acyl tails of the phospholipids through hydrophobic interactions, anchoring the protein in the membrane. Peripheral membrane proteins, by contrast, associate with the polar head groups through electrostatic and hydrogen bonds and are easily displaced.

Question 19

Investigators report that for a group of patients the average diastolic blood pressure is 113 mm Hg, with a 95% confidence interval of 110 to 116 mm Hg. If the investigators instead wished to report a 99% confidence interval using the same data, which of the following would most likely be true of the new interval?

Accepted Answer

B. It would be wider and still centered on 113 mm Hg. A confidence interval is centered on the sample mean and has a half-width equal to the critical value times the standard error. Raising the confidence level from 95% to 99% increases the critical value (from about 1.96 to about 2.58 standard errors) while the mean and standard error are unchanged, so the interval gets wider but stays centered on 113 mm Hg. Greater confidence requires a wider interval to be more certain it captures the true mean.

Question 20

A couple seeks counseling before conception. The man has two siblings with cystic fibrosis but is himself unaffected. The carrier frequency for cystic fibrosis in the general population is 1 in 25. Assuming the woman is from the general population, which of the following best approximates the probability that this couple will have a child with cystic fibrosis?

Accepted Answer

B. 1 in 150. Because the man is unaffected but has affected siblings, his probability of being a carrier is 2/3 (the affected genotype is excluded from the four possibilities of two carrier parents). The woman's carrier probability is the population value of 1/25. If both are carriers, the chance of an affected child is 1/4. Multiplying gives 2/3 times 1/25 times 1/4, which equals 2/300, approximately 1 in 150.

Question 21

A 45-year-old woman is scheduled to undergo a lymph node biopsy under local anesthesia. A surgical resident asks a third-year medical student to obtain the patient's signed informed consent before the procedure. The student has observed the procedure once but has not performed it and is not familiar with its risks. Which of the following is the most appropriate action by the student?

Accepted Answer

B. Decline and explain that consent should be obtained by a provider who can describe the procedure, its risks and benefits, and alternatives. Informed consent must be obtained by someone with enough knowledge of the procedure to describe its nature, the risks and benefits, and the alternatives, and to answer the patient's questions. A student who is unfamiliar with the procedure cannot fulfill this requirement, so the appropriate response is to decline and explain that a qualified provider should obtain consent. This protects the patient's autonomy and the validity of the consent rather than simply refusing all involvement.

Question 22

A medical student is caring for a 72-year-old man admitted with a lung mass. Biopsy shows carcinoma, but the resident instructs the student not to inform the patient of the results until the oncologist sees him the next day. The next morning the patient asks the student, "What did my biopsy show?" Which of the following is the most appropriate response by the student?

Accepted Answer

D. "Let me get the resident physician so we can go over the results together.". The student should neither lie to the patient nor deliver complex, life-changing results beyond their role and knowledge. The best response acknowledges the patient's question honestly and brings in the responsible physician so the information is conveyed accurately and with appropriate support. Falsely reassuring the patient or stating the results are not back is dishonest, and a student disclosing the cancer diagnosis alone risks miscommunication and oversteps their role.

Test	Result
Platelet count	18,000 /mm3
Hemoglobin	12.5 g/dL

Test	Result
MCV	68 fL
Ferritin	Normal

Test	Result
Temperature	38.4 °C
WBC	14,000 /mm3

Test	Result
Sodium	128 mEq/L
Potassium	6.1 mEq/L
17-OH-progesterone	Elevated

Free USMLE Step 1 sample questions

Human Development

Blood & Immune Systems

Behavioral Health & Nervous Systems

Musculoskeletal, Skin & Subcutaneous Tissue

Cardiovascular System

Respiratory & Renal Systems

Gastrointestinal System

Reproductive & Endocrine Systems

Multisystem Processes & Disorders

Biostatistics & Epidemiology

Free USMLE Step 1 sample questions

Human Development

Question humdev-001: Human Development

Question humdev-002: Human Development

Blood & Immune Systems

Question blood-001: Blood & Immune Systems

Question blood-002: Blood & Immune Systems

Behavioral Health & Nervous Systems

Question neuro-001: Behavioral Health & Nervous Systems

Question neuro-002: Behavioral Health & Nervous Systems

Musculoskeletal, Skin & Subcutaneous Tissue

Question msk-001: Musculoskeletal, Skin & Subcutaneous Tissue

Question msk-002: Musculoskeletal, Skin & Subcutaneous Tissue

Cardiovascular System

Question cardio-001: Cardiovascular System

Question cardio-002: Cardiovascular System

Respiratory & Renal Systems

Question resp-001: Respiratory & Renal Systems

Question resp-002: Respiratory & Renal Systems

Gastrointestinal System

Question gi-001: Gastrointestinal System

Question gi-002: Gastrointestinal System

Reproductive & Endocrine Systems

Question repro-001: Reproductive & Endocrine Systems

Question repro-002: Reproductive & Endocrine Systems

Multisystem Processes & Disorders

Question multi-001: Multisystem Processes & Disorders

Question multi-002: Multisystem Processes & Disorders

Biostatistics & Epidemiology

Question biostat-001: Biostatistics & Epidemiology

Question biostat-002: Biostatistics & Epidemiology

Social Sciences & Communication

Question social-001: Social Sciences & Communication

Question social-002: Social Sciences & Communication