Explanations for the 2021 Official Step 1 Practice Questions

This year’s set was updated in February 2021 (PDF here).

The asterisks (*) signify a new question, of which there are only 2 (#24 and 53). The 2020 set explanations and pdf are available here; the comments on that post may be helpful if you have questions.

The less similar 2019 set is still available here for those looking for more free questions, and even older sets are all listed here. The 2019 and 2020 sets, for example, differed by 36 questions (in case you were curious).


Block 1

  1. B – In addition to penicillin, the treatment paradigm for step viridans endocarditis also includes the aminoglycoside gentamicin, which binds to the 30S subunit and accelerates bacterial clearing/decreases treatment duration.
  2. A – Intermittent hyperbilirubinemia/jaundice in an otherwise healthy individual is typical of Gilbert’s syndrome, which is caused by the decreased activity of UDP glucuronosyltransferase.
  3. C – Acetylcholine increases after drug X, which is the same we’d expect if drug X were a cholinesterase inhibitor.
  4. C – The purpose of Rhogam is to bind to and remove the RhD antigens so that the mother does not form an immune response against the antigen in the fetus’ blood. It’s given to at-risk Rh- moms at 28 weeks and at delivery.
  5. A – Electrical alternans on boards means a big pericardial effusion (and usually cardiac tamponade physiology). The heart cannot fill properly, preload decreases, hypotension and tachycardia ensue, fluid backup leads to elevated JVP. Underlying etiology in this patient is renal failure (uremia).
  6. C – Metformin is awesome. It decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
  7. C – His leukocyte count is normal, so he’s not at risk for opportunistic infection, but his platelets are low, placing him at risk of bleeding. Petechiae are common in thrombocytopenia. DVT (A) is the opposite problem, a thrombophilia. Joint hemorrhage (hemarthrosis), nail bed hemorrhage, and frank visceral hematomas are more commonly seen in hemophiliacs.
  8. C – Serum sickness! A type III (immune complex) hypersensitivity.
  9. A – Narcotic use for acutely painful conditions is both reasonable and important. (Very) short-term use (immediately post-surgical) does not lead to long-term dependence (or so people have thought…). And yes, even someone who uses and/or is dependent on illicit drugs should also receive narcotics to control pain.
  10. B – Contract dermatitis is a type IV (T-cell mediated) hypersensitivity. T-cell CD28 activation through binding CD80 (part of the B7 group) on the APC is the dominant interaction in T-cell hypersensitivities/allergies.
  11. A – Malonyl-CoA inhibits the rate-limiting step in the beta-oxidation of fatty acid. Logically, resting muscle requires less energy (and thus less need for fatty acid breakdown) than active muscle.
  12. C – This is obviously a clinical trial. If you know you are getting a drug, then you are not blinded: it’s an open-label trial. There is no randomization as there is only a single treatment group.
  13. B – Don’t let them blind you with this patient’s misery. The issue of the day is that he has a DVT. That’s why he came to the ER in the first sentence and what the ultrasound shows at the end. Patients with cancer are hypercoagulable.
  14. C – Leydig cells make testosterone. Leydig cell tumors aren’t always physiologically active, but those that are can cause masculinization. Granulosa cell tumors, on the other hand, sometimes produce estrogen (which can lead to precocious puberty in young girls but otherwise may be occult). Teratomas are oddballs that typically have fat, hair, teeth, etc. Thecomas will not be on your test. Ovarian carcinoid is highly unlikely to show up on your test, but if it did, it would likely present with a classic carcinoid syndrome.
  15. E – Endothelial tight junctions’ permeability is increased in response to injury and inflammation, allowing migration of white blood cells and friends to the site of injury.
  16. D – Pineal region tumors cause obstructive hydrocephalus due to their proximity to the third ventricle. But in this case, we’re being tested on pineal region tumors’ propensity to cause Parinaud’s syndrome due to compression of the midbrain tectum.
  17. A – The CT scan showed “wedge-shaped areas of hypodensity,” which are renal infarcts (wedge-shaped = vascular territory). Renal infarcts are commonly caused by emboli from atrial fibrillation, just like a fib can result in emboli in other areas like the brain or limbs.
  18. D – Hot tub folliculitis, it’s a thing. Classically pseudomonas.
  19. A – As always, it’s almost better to ignore the pictures when possible. This gentleman has a peptic ulcer, which we know is caused predominately by H. pylori infection. H. pylori produces proteases, particularly urease, which allow it to increase the pH of its local environment by cleaving urea into ammonia, which is toxic to gastric mucosa. The picture demonstrates H pylori, which are evident with silver staining.
  20. A – Basic nerve anatomy and function.
  21. C – The Pouch of Douglas is the space between the uterus and the rectum (i.e. the place where pelvic free fluid goes).
  22. F – DMARDs used for ankylosing spondylitis are typically the same anti-inflammatory anti-TNF drugs used for other inflammatory conditions like IBD, RA, psoriasis, etc (e.g. adalimumab, etanercept, infliximab, etc.).
  23. A – A new blistering disease in an older person is typically going to be a pemphigus question. Then you just have to remember the difference between bullous pemphigoid vs pemphigus vulgaris. Bullous pemphigoid is characterized by the loss of hemidesmosomes that bind keratinocytes to the basement membrane, resulting in bulla (big blisters) in areas of friction, choice A. Patients with pemphigus vulgaris lose their desmosomes (which bind keratinocytes to each other), so that their skin is super friable, which results in ulceration. Mouth ulcers are more common in PV.
  24. B – Acetaminophen is the leading cause of acute liver failure in the US and causes liver necrosis. Fewer functioning liver cells means fewer cells able to conjugate bilirubin, which means more unconjugated bili floating around to cause jaundice. Note that glutathione is conjugated to remove acetaminophen’s toxic metabolite NAPQI, and its depletion is what allows said metabolite to damage the liver.*
  25. B – They have described what you assume is a classic case of pneumonia. But, PNA isn’t an answer choice. What the next best thing? The cause! Old frail people (and alcoholics) love to get aspiration pneumonia. RLL is the most common site, which they have provided (thank you, big vertical bronchus). They even gave you the hint that the patient has “difficulty swallowing,” which is code for “aspirates when swallowing.”
  26. E – Acknowledge, please.
  27. E – No relation between the atrium (P) waves and the QRS complex means third-degree AV block (aka “complete” heart block). Symptomatic (even fatal) bradycardia can result. “Cannon” a(trial) waves are prominent jugular venous pulsations that occur when the atria and ventricle contract simultaneously (which, of course, doesn’t normally happen).
  28. E – Functional parathyroid adenomas can cause elevated parathyroid hormone (PTH), which results in hypercalcemia and hypophosphatemia. Hypercalcemia is characterized by the rhyming symptoms: stones (renal, biliary), bones (including bone pain to osteitis fibrosa cystica), groans (abdominal pain, n/v), thrones (polyuria, constipation), and psychiatric overtones (from depression to coma).
  29. C – Stroke characterized by left hemiparesis and right CN12 palsy. Crossed findings mean a brainstem lesion. Right (ipsilateral) tongue, left-sided (contralateral) weakness means the exiting right hypoglossal nerve has been affected (within the right medulla). C is the pyramid where the corticospinal tract runs to control muscles (prior to the decussation). This is known as the medial medullary syndrome or Dejerine syndrome.
  30. C – Acknowledge and explore, please.
  31. C – Southern blots are commonly used in immunological studies, as the southern blot allows for the study of DNA alterations. What is normally one gene configuration related to immune globulins in most tissues demonstrates multiple different bands in the bone marrow, indicative of gene rearrangement. This is basically how we create new antibodies. Reactive processes are polyclonal (multiple bands); leukemia, in contrast, is monoclonal (single band).
  32. A – Androgen insensitivity is caused by a defective androgen receptor. DHT is responsible for creating male genitalia during fetal sexual development. The default human gender is female. So a genetically male patient with complete androgen insensitivity is externally phenotypically female. Lack of response to adrenal androgens prevents hair formation during puberty (adrenarche).
  33. C – While E coli is normal gut flora, your body would prefer it stay intraluminal.
  34. A – Patient-centered care means empowering patients to make their own medical decisions. It’s important to check-in and get a feel for their level of understanding and thoughts about potential treatment options.
  35. B – Absolute risk reduction is the decrease in the number affected per number exposed = (15-5)/50 = 10/50 = 0.2.
  36. B – Hep C infection results in chronic viral injury. The viral (“foreign”) peptides bind to class I MHC (the endogenous/intracellular type) and then get attacked by CD8+ killer T-cells. Class II MHC are those found on professional APCs, not regular tissues. CD4+ are helper T-cells and do not cause in direct cell injury.
  37. A – The baroreceptors are stretch receptors that fire more frequently with increasing wall stress/distention. In chronic hypertension, the body gets used to the increased pressure and as a result moves the normal “set point” to the right, meaning that the baroreceptors will fire less for a given degree of stretch. Note that even if you didn’t understand this nuance that the other choices are clearly the opposite of true.
  38. E – The patient’s chronic inflammatory pneumonitis is killing off his lung parenchyma (composed primarily of type I pneumocytes). Type II pneumocytes, in addition to making surfactant, can replicate in order to replace type I pneumocytes, so they will be increased. Chronic interstitial inflammation results in fibrosis, hence an increase in fibroblasts.
  39. E – Gram-positive rods in a diabetic foot wound (or a World War I soldier fighting in a trench) signify Clostridium perfringens (the causative organism of gas gangrene). Crepitus means gas in the tissues, which is produced as a byproduct of its highly virulent alpha toxin.
  40. B – Skin involvement is an early and common manifestation of GVHD.

Block 2

  1. B – The left-sided system is much higher pressure than the right side, hence the aortic valve closing is usually louder than the pulmonic valve. A P2 louder than A2 means that the pulmonary arterial pressure is significantly elevated.
  2. A – You’re not supposed to drink on Flagyl (metronidazole) because it causes a disulfiram-like reaction by interfering with aldehyde dehydrogenase, which results in a build-up of acetaldehyde.
  3. A – The infraspinatus and teres minor are responsible for external rotation. Both the infraspinatus and supraspinatus muscles are innervated by a suprascapular nerve.
  4. D – Vincristine’s general MOA is to inhibit microtubule formation in the mitotic spindle. With regards to neuropathy, vincristine induces axonal neuropathy by disrupting the microtubular axonal transport system. Just remember the magic word: microtubules.
  5. B – A genetic variation in a particular nucleotide is by definition a polymorphism. Note that the question specifically states that it does not change the protein.
  6. E – Excuses and critique don’t make people feel better. You’ll never get good Press Gainey scores by calling out their bullshit like that.
  7. D – The baroreceptors are stretch receptors (the more fluid in the vessel, the more they fire). So a patient with hemorrhagic shock will see a decrease in the baroreceptor firing rate. Activation of RAAS will result in increased vascular resistance (vasoconstriction) in order to maintain blood pressure. And capillaries, such as those in the kidney, will be primed for resorption and not filtration (no one wants to pee out good dilute urine when they’re dehydrated). Likewise, systemic capillaries will prefer to hold onto plasma and not let it leak into the interstitium (third-spacing).
  8. D – The arrowed fluid is contained in a space behind the stomach but in front of the retroperitoneal structures (e.g. the pancreas), i.e. the lesser sac.
  9. C – They are asking for the positive predictive value. PPV = True positive/all positive or PPV = TP/(TP+FP).
  10. D – You need to use a professional interpreter. It’s a rule.
  11. D – If the fluid keeps coming into the glomerulus (via the afferent arteriole), but you clamp the exiting vessel (the efferent arteriole), then it’s going to build up in the glomerulus, leading to increased hydrostatic pressure (as well as increased filtration fraction).
  12. E – Fragile X is a CGG trinucleotide repeat expansion disorder (which like Huntington’s is a test favorite). The maternal uncle is the hint to the X-linked inheritance. Autism-like behaviors and relatively large head are common; large testicles only appear after puberty.
  13. C – This question is asking for the vascular supply of the parathyroid glands. That would be the inferior thyroid arteries, which arise from the thyrocervical trunk.*
  14. A – Thiazide diuretics work on the NaCl symporter. Like all diuretics except for “potassium-sparing” ones, they can cause hypokalemia.
  15. E – Splitting is an immature defense mechanism often employed by patients with borderline personality disorder. When splitting, a person fails to see others as capable of having both positive and negative qualities; at any given time, it’s all or nothing.
  16. B – This is a (prospective) case series. There is no control group (and certainly no blinding).
  17. C – Like chronic granulomatous and its deficient superoxide formation, myeloperoxidase deficiency (inability to form hypochlorite) also results in the inefficient killing of phagocytized organisms. The main clinical distinction is that myeloperoxidase deficiency is generally much less severe and less commonly involves recurrent serious bacterial infections. Instead, when symptomatic it typically involves runaway candida infections.
  18. A – Oral vesicle (hint hint). Blistering vesicular lesion on the hand. No fever, not toxic-appearing. This is Herpes (you may remember dentists getting herpetic whitlow in your studies, which is what this is). Most folks get HSV1 as children, though obviously, not all are symptomatic. HSV is a large double-stranded, linear DNA virus.
  19. C – Brutal knock on Kentucky as a place where children play in and eat mud. Ascariasis is typically from eating delicious mud or contaminated farm stuffs, etc, whereas hookworm is from direct skin penetration. Both parasites can cause abdominal pain and diarrhea, among other symptoms, but ascariasis can also result in pooping worms.
  20. A – Gonorrhea can change its pilus, which is responsible for adhesion to host cells and the main antigen to which the host mounts an immune response. Neisseria gonorrhoeae is able to switch out different pilin genes, and for this reason, prior infection does not confer long-lasting immunity.
  21. E – DMD is X-linked. We know her mom is a carrier based on family history, supported by lab testing. But her mom has 2 X chromosomes, only one of which is mutated. There is no way to know which her daughter eventually receives and expresses by her phenotype (i.e if she is a carrier or not). Just because her CK is normal doesn’t mean she isn’t a carrier–the phenotype of the X-linked carrier depends on X-inactivation.
  22. E – von Willebrand disease is by far the most common inherited bleeding diathesis. Frequently, the only laboratory abnormality is increased bleeding time (literally you prick the patient and see how long it takes them to stop bleeding). On Step, bleeding women have VWD. Bleeding boys have hemophilia.
  23. B – Blood at the meatus is the red flag (see what I did there?) for urethral injury, which should be evaluated for with a retrograde urethrogram. The membranous urethra is the most commonly injured by fracture. In contrast, the spongy urethra is most likely to be injured during traumatic catheter insertion or in a straddle injury.
  24. B– The arrow is pointing to a neutrophil (multilobed nucleus): main fighter of the immune system in acute inflammation and bacterial infection (such as aspiration pneumonia). C5a is a chemotactic factor for PMNs.
  25. B – The proliferative phase of the menstrual cycle is controlled by cyclin-dependent kinases.
  26. D – Carbamazepine is a notorious CYP450 inducer, so you should be guessing metabolism no matter what. CYP450 plays an important role in both vitamin D bioactivation and degradation in the liver.
  27. D – Toxic shock syndrome. Rash involving the palms and soles is the most unique feature, though the question lists them all. While it is not actually limited to tampon-using menstruating females, that is the most common setting.
  28. D – Below the dentate line, anal cancer drainage is superficial inguinal. Above the dentate line, superior rectal (then iliac).
  29. E – Pubertal gynecomastia in males is normal and generally goes away on its own. If “normal” is an answer choice, make really sure you don’t want to pick it.
  30. E – Left orbital floor fracture involving the infraorbital foramen. This carries a branch of the maxillary nerve (V2), the infraorbital nerve, that is responsible for sensation of the upper lip.
  31. E – Marathons are hard, but I wouldn’t know first hand. (Post-exertional syncope typically occurs when exercise is stopped suddenly and the reduction of lower extremity muscle pumping results in less cardiac venous return and cardiac output via the Starling mechanism. This can result in orthostatic hypotension [especially when dehydrated] and consequent transient global cerebral hypoperfusion).
  32. D – Meckel’s diverticulitis. Antimesenteric thingie near the terminal ileum is about as good of a location giveaway as you’re going to get (no one is going to toss the whole Rule of 2’s in a stem). Recurrent bleeding episodes, as helpfully referenced in the history, are secondary to acid-producing ectopic gastric mucosa.
  33. A – Acting out aka “being a teenager.”
  34. A – Of the choices provided, only ACE inhibitors are known to cause fetal renal damage. The data on first-trimester organ dysgenesis is not clear cut, but second- and third-trimester renal injury is unequivocal.
  35. B – Aspirin-exacerbated respiratory disease, a common acute worsening of asthma after aspirin use. COX-1 inhibition from ASA and NSAIDs can shunt inflammatory precursors down the leukotriene production pathway. This can be alleviated by leukotriene inhibitors like montelukast.
  36. C – It’s critical to meet the patient where they are and explore their understanding of their disease and treatment. It’s exceedingly common for people to misunderstand preventative or prophylactic medications because they have no immediate effects (i.e. “I tried it and it didn’t work”). This is a problem with asthma, migraine prophylaxis, antidepressants, etc.
  37. C– Approximate fasting physiology timing: the post-absorptive phase (6-24 hours after a meal) is dominated by glycogenolysis. Gluconeogenesis from 24 hours to 2 days. Then ketosis.
  38. B – Crohn’s: skip lesions, fistulae, strictures (and the unnecessary transmural involvement on histology).
  39. A – That poorly oxygenated “chocolate” brown blood is a sign of methemoglobinemia. This results when the reduced ferrous [Fe2+] state is oxidized to the ferric [Fe3+] state, because ferric iron is unable to bind and transport oxygen, resulting in a functional anemia. The congenital version is sometimes called Hemoglobin M disease, though it can also be acquired in the setting of certain exposures like nitrite preservatives.
  40. D – Hemolytic strep means either Group A or Group B. GAS are killed by bacitracin; GBS are resistant.

Block 3

  1. B – Bisphosphonates work by decreasing osteoclast activity (thereby reducing bone resorption). Choice F is the opposite of how estrogen therapy works (RANKL is found on osteoblasts, and its activation triggers osteoclasts and stimulates bone resorption).
  2. D – An odds ratio greater than 1 signifies increased odds/risk/likelihood. If the 95% confidence interval range does not include 1, then the difference is statistically significant (though not necessarily clinically meaningful).
  3. B – (Unstable) angina. Most immediate treatment is nitro.
  4. E – VEGF is a major tissue growth factor activated by injury, cytokine release (infection, inflammation) and hypoxia that promotes angiogenesis and also increases vascular permeability (hence the edema). This increased permeability aids in the movement of proteins and white blood cells to the site of injury.
  5. A – DI is an important complication of some skull base fractures and can be treated with DDAVP. You probably remember that this works via the activation of aquaporin channels, but these are moved from intracellular vesicles to the apical membrane surface as a result of a DDAVP-mediated increase adenylate cyclase via a stimulatory G protein that increases intracellular cAMP.
  6. D – He has (presumably RSV) bronchiolitis. RSV is an RNA virus that enters the cell via a fusion protein (which is the target of the prophylactic monoclonal antibody drug Palivizumab).
  7. D– A b2 agonist like the bronchodilator albuterol would sure help that wheezing. Note that epinephrine (such as in an epi-pen) would also achieve this but is nonselective; in this case, the patient’s symptoms would be helped most by the beta-2 component.
  8. C – Just because he’s having (unprotected) sex doesn’t mean he doesn’t have simple infectious mononucleosis. The sex implies he’s also kissing someone! Pharyngitis + lymph nodes + fatigue = mono.
  9. B – p53 is an important tumor suppressor gene, particularly in its ability to cause a cell to undergo apoptosis in the event of damage. p53 activity also holds the cell at the G1/S regulation point (B), limiting DNA synthesis.
  10. D – Schistosomiasis is a parasitic worm particularly endemic in Africa (Egypt, in particular, comes up the most on questions) that is most associated with chronic cystitis. Calcifications of the bladder wall are essentially pathognomonic. Chronic infection is associated with an increased risk of squamous cell carcinoma of the bladder (as opposed to the usual urothelial/transitional cell).
  11. C – The mom will pass on her deletion in 50%. The father will pass it on in 100% (because both of his copies are affected). Therefore, the child will automatically have at least one deletion and will have the double deletion in 50%.
  12. C – TTP has a classic pentad: microangiopathic hemolytic anemia, thrombotic purpura, fever, renal failure, neurologic abnormalities (AMS). Whenever you see a question where the patient suddenly has a lot going on, consider TTP.
  13. A – Air and fluid = hydropneumothorax. If that fluid is blood (s/p stabbing), it’s a hemopneumothorax. Lack of mediastinal shift indicates that it’s not under tension.
  14. C – Statins raise HDL and decrease LDL and TGs. Their effect on LDL is by far the most potent, but they do a little good on everything.
  15. E – Subacute combined degeneration (progressive peripheral sensory and motor loss) is a late sign of B12 deficiency, which is common in old people. On exams, a geriatric patient who lives alone and may have a “tea and toast” diet is likely to have vitamin deficiencies, particularly of folate and B12.
  16. E – Androgens stimulate sebaceous glands and cause acne. In girls, this is primarily due to adrenarche (DHEA/DHEAS androgen production made by the adrenal gland the zona reticularis). Boys can also blame testosterone from gonadal puberty (pubarche).
  17. A – Endemic Burkitt lymphoma can happen in Brazil as well as Africa (jaw lesion, puffy face). The photomicrograph is demonstrating tingible body macrophagesa type of macrophage containing many phagocytized, apoptotic cells in various states of degradation.
  18. D – Many oral cavity lesions, especially anteriorly such as the tip of the tongue, drain first to submental nodes (level 1). Oropharyngeal SCCs most commonly drain to level 2.
  19. E – CNS amoebiasis is most notoriously caused by Naegleria fowleri, which I encourage you to memorize as the “brain-eating amoeba.” Found in fresh-water bodies of water like ponds and lakes, it has three forms: a cyst, a trophozoite (ameboid), and a biflagellate (i.e. has two flagella). Infection is via olfactory cell axons through the cribriform plate to the brain.
  20. E – PCP is a sedative-hypnotic and dissociative anesthetic that generally acts as a downer but can also cause incredible aggression coupled with pain insensitivity (the superman drug). Vertical nystagmus is a commonly mentioned physical exam finding.
  21. A – The alpha-value corresponds to the p-value we will accept as significant and reflects the likelihood of a type I error (a false positive). A lower alpha-value means a lower acceptable likelihood of obtaining the same results by chance, and thus, significant results can be reported more confidently (a 1% false-positive rate instead of a 5% rate).
  22. B – Anorexia leads to hypogonadotropic hypogonadism, as the body realizes that the possibility of nourishing a fetus is zero and gives up the pretense. There’s a lot of supporting data, but one should guess this answer once you read the word “gymnast” (or “dancer”).
  23. C – Swallowing amniotic fluid is a critical component of lung development. Fetuses with severe oligohydramnios are plagued by pulmonary hypoplasia, which is the cause of death in fetuses born with Potter syndrome (renal agenesis).
  24. B – What we have here is a congenital intolerance to breast milk: galactosemia, in which the body cannot convert galactose to glucose (resulting in an accumulation of Galactose 1-phosphate). They then list the findings and tests used to diagnose it. Lactose (the disaccharide in milk) is composed of glucose + galactose.
  25. E – When people go camping, you should be thinking of zoonotic infections. Fun fact, New Mexico leads the country in cases of plague. Yes, that plague: Yersinia pestis. The “bubonic” part of bubonic plague refers to the swollen infected nodes (“buboes”) characteristic of the disease, which often involve the groin (bubo is the Greek word for groin, who knew?). In this case, they’re also describing a necrotic epitrochlear node. Classic treatment is with aminoglycosides, which bind to the 30s ribosomal subunit. (Note that Tularemia, caused by another gram-negative bacteria Francisella tularensis can present similarly but is more common in the midwest. Regardless, the two are often lumped together, the antimicrobial treatment is similar, and the answer in this case would be the same).
  26. A – Middle-aged person with a progressive weakness including a likely mix of UMN/LMN signs (weakness, fasciculations) is concerning for ALS (amyotrophic lateral sclerosis) aka Motor Neuron Disease aka Lou Gehrig’s disease. Several of the other choices are possible but none as universally present as muscle atrophy.
  27. A – The main downside of live vaccines is that they rarely cause the disease they’re designed to prevent, typically in immune-compromised individuals (who either get the vaccine or are in close contact to someone who does).
  28. A – p53 is the quintessential tumor suppressor (it activates apoptosis). HPV carcinogenesis is caused by insertion of the virus into host DNA that produces a protein which binds to an essential p53 substrate, functionally inactivating p53 and preventing its apoptotic cascade. C (transactivation/TAX) is how HIV and HTLV cause cancer. E (c-myc translocation) causes Burkitt lymphoma.
  29. A – Erythropoietin does those things. It (or a comparable drug) is also given to basically all dialysis patients to combat anemia of chronic disease. On a related note, you should also recall that JAK2 mutations can cause polycythemia vera.
  30. F – Total peripheral resistance goes down during exercise as the arterioles supplying muscle and skin dilate.
  31. A – The usual cold-like symptoms of runny eyes and a sore throat are common of several strains of adenovirus that are readily communicated amongst humans in close contact.
  32. B – She has Cushing’s syndrome with classic red/purple abdominal striae (aka “stretch marks”), truncal obesity, and moon facies. Increased levels of the stress hormone cortisol often result in hypertension, and muscle wasting is common in this runaway catabolic process resulting in weakness.
  33. C – Osgood-Schlatter is also known as apophysitis of the tibial tubercle. It’s due to chronic stress/irritation at the insertion of the patellar tendon on the tibial tubercle. It’s classically seen in teenagers doing repetitive vigorous activity (running, jumping). The radiograph demonstrates classic fragmentation of the tibial tubercle (which isn’t necessary to recognize to get the question correct).
  34. D – Radon is a radioactive gas and common ground contaminant. Given off by soil, it’s heavy and is thus typically concentrated in basements. That said, this question is garbage: wood dust is also a known carcinogen.
  35. A – Fear = amygdala
  36. E – Cystic fibrosis is an autosomal recessive disease involving CFTR, which means you need a double hit to express the disease. If the genetic test only picked up one, then it must have missed the other.
  37. E – What terrible machine learning algorithm wrote these other answer choices?
  38. E – If you ever had a child or spent time with someone who has, you would know this is stone-cold normal. Remember, if normal is an answer choice, the default answer is to pick it unless really convinced otherwise.
  39. A – Early-onset tremor with presumed autosomal dominant inheritance (and successively earlier ages of onset aka “anticipation”) with associated psychiatric disturbances and likely early death is concerning for Huntington’s disease. Involvement is centered in the basal ganglia, particularly the caudate. Resting tremor is most commonly Parkinson’s. Intention tremors (resulting in zig-zagging as the patient tries to hone in on the target) and dysmetria (i.e. over/under reaching) are most commonly a result of a cerebellar process such as a stroke.
  40. The multimedia cardiac exam question: I’m going to point out that a normal healthy kid with no cardiac history or symptoms and no family history of sudden cardiac death for a pre-sports physical is probably going to have a benign exam no matter what you think you hear.

Errata and requests for further clarification etc can be made in the comments below.

You may also enjoy some other entries in the USMLE Step 1 series:
How to approach the USMLE Step 1
How to approach NBME/USMLE questions
How I read NBME/USMLE Questions
Free USMLE Step 1 Questions


Jonny Hatch 05.26.21 Reply

Thank you! Extremely helpful. Can you explain why Q#:71 would not be hyponatremia? Is it because she has normal mental status?

Ben 05.26.21 Reply

More of a “single best answer” thing. She could have hypovolemic hyponatremia, which would contribute to orthostasis, but her post-exertional syncope isn’t really secondary to hyponatremia per se, it’s directly a manifestation of orthostatic hypotension.

If you stand up quickly and pass out due to hypotension that improves when you recline, you have orthostatic hypotension. Even if you are dehydrated or have an underlying heart condition that explains why you are orthostatic, that doesn’t change the fact that it’s what happened to you.

We often talk about ruling out distractors when taking Step questions, but really, the other answer choices don’t need to be wrong for them not to be the best.

Shannara 05.29.21 Reply

This was super helpful thank you! I also appreciate the funny commentary. Much better than reading dry question explanations. I did notice you left out #120. Not sure if that was on purpose or not. Thanks again for all your help!

Ben 05.29.21 Reply

Hmm, the PDF online for me ends at 119 for me this year. In past years there were 120 though yeah. (I haven’t looked at the online version/ multimedia questions.)

Joshua 06.10.21

There is one multimedia question involving chest auscultation of a child that is only available if you go to the testing center for the Free 120 as far as I know. That is the missing question. The question had audio of a fixed split and a loud S2. The answer was increased pressure in pulmonary artery. Due to the Eisenmenger syndrome from the ASD.

Paige C 06.22.21

the online free 120 has the audio auscultation as the last q in a 14 yo boy with history of otitis media and tonsillectomy for OSA….and it says the answer is “normal findings”

Stephen 07.02.21

100% agree with Shannara here. I appreciate the funnies. Also, you may have looked at it by now, but the last question has media so thats probably why its not on the PDF. But it’s just normal heart sounds. Mostly just wanted to say thanks for making it slightly entertaining.

Ben 07.05.21

I finally went back to add it. For me, it’s the normal kid sports physicial question (which is a repeat from way back in 2017).

Jas 06.02.21 Reply

This was super helpful and super fun to read. Always enjoy a good, sassy explanation. Thank you!

Ben 06.08.21 Reply

Definitely no way I could provide this service without being sassy.

Christina 06.07.21 Reply

These answers are SO much better than Uworld and NBME haha – they’re easy on the eyes and bring some joy into the oh so unjoyful STEP study life. Thank you for doing this!

Ben 06.08.21 Reply

You’re very welcome, glad they were helpful.

Tayo 06.10.21 Reply

God bless you sir! These were simple and straightforward and made the review process a bit more bearable! Thanks for doing this!!

Jesse 06.17.21 Reply

Thanks so much, Ben! I found these entertaining to read and appreciated the humor and how straight and to-the-point your descriptions were. Keep up that sass.

For anyone looking for the explanation to the missing audio question (#120), the answer is E, normal findings (verified on the answer key available at the end of the exam). The patient has S2 splitting during inspiration at the pulmonic region that disappears upon expiration (physiologic, due to increased venous return to the heart during inspiration and more blood flow through pulmonic valve/delayed closing after aortic valve). Good luck to everyone taking Step 1! :)

Matty 06.19.21 Reply

Thank you for doing this! For question 10, I had a hard time choosing between T cell CD28 and APC CD80 or T cell CD40L and APC CD40. First aid says macrophages also use CD40 as a costimulatory signal with T cells. Is there anything that makes CD28 and CD80 more accurate for this scenario?

Joseph HQ 06.20.21 Reply

is CD40 and CD40L for B-cell costimulation?
I think CD28 and CD80 may be fore T-cell costimulation specifically.

Ben 06.20.21 Reply

Correct, CD40 is part of the B-cell activation pathway.

Alexis 06.21.21 Reply

Thank you for doing this the explanations are great.

For number 54, I ended up steering away from the correct answer (adverse drug effect) because they have a 10 year history. Why would it take up to 10 years to start showing symptoms of hypokalemia? Wouldn’t this have been caught earlier? Why wouldnt alcohol be a sufficient choice?


Ben 06.21.21 Reply

Low blood pressure and chronic symptoms of hypokalemia would make more sense for drug effects than alcohol “intoxication,” which she presumably is not at all times including during the visit in question despite her history of concerning use.

Razan 06.24.21 Reply

Thank you so much! That was helpful 🤩

Sarah 06.27.21 Reply

Thank you for the explanations!
for block 1, question 32:
For a CAH 17-alpha hydroxylase deficiency in a female, wouldn’t that present the same? lacking secondary characteristics…. but is it the breast development being normal that makes androgen sensitivity more likely? because without a pelvic exam or genetics given XX/XY, how can you differentiate the two?

Thank you!

Ben 06.30.21 Reply

Correct complete 17alpha CAH do not have breast development (partial can have some).

Probably more importantly, the question refers to CAH in general, and the classic congenital adrenal hyperplasia due to 21-​hydroxylase deficiency results in virilization.

Mangun Kaur 07.12.21 Reply

Q72 isn’t Meckel’s diverticulum an example of a choristoma? Technically this had two right answers..

Ben 07.12.21 Reply

No, a choristoma is a benign tumor/mass.

Tommy 10.12.21 Reply

Heterotopic tissue (wrong place/right tissue) is usually the descriptor they like to use for Meckel’s.

JuanPCol 11.05.21 Reply

I think you are right. Actually I believe I came across a question on UWSA2 regarding choristomas and they listed Meckels diverticulum and Endometriosis as examples of choristomas (healthy tissue in wrong place). Although correct, most of the time the most obvious/logical option is the right one, so “gastric mucosa? Why not!?” that was my approach lol

Ben 11.05.21

For those curious and wanting further convincing, recall the suffix -oma means “swelling” or “mass” or “tumor.” This is why cancers are called things like carcinoma and sarcoma and fatty tumors are called lipomas etc etc etc. You can indeed have “endometriomas” so that usage would be correct.

Nomenclature is boring, but outside of eponyms, it usually isn’t arbitrary.

Yusuf 04.19.22 Reply

Just realized First Aid does give Meckel as an example for choristoma on page 220. Although after further invetigation, it doesn’t appear 100% accurate since it isn’t really an overgrowth.

Amanda 07.14.21 Reply

Thank you so much! This was super helpful to me. Two comments – in #106 I believe weakness and fasciculations are both LMN symptoms, lending even more support to atrophy as the correct answer (UMN lesions lead more to hypertonia before eventual atrophy). In #118 I think the point they were trying to make was that the baby was premature, so it is normal for development to be slightly delayed. Totally agree with your advice about leaning toward normal until proven otherwise though!

Ben 07.14.21 Reply

Weakness is both UMN or LMN (e.g. a stroke causes weakness).

Vincent 08.30.21 Reply

I thoroughly enjoyed reading these explanations, like, genuinely had a good time. This is awesome and makes me think uworld needs to make their explanations more like these lol. Cheers.

kim 03.04.22 Reply

I couldn’t agree more. Thanks so much!

Akshita 10.20.21 Reply

This was extremely extremely helpful. Thank you so much

Cornflakes124 10.23.21 Reply

For Block 1 Q31: Personally, I was torn between C and D (alternative splicing) – what helped me choose C in the moment of panic was that this is a southern blot –> Always detects DNA and cannot detect RNA (Northern Blot), hence D couldn’t have been the answer. Just an alternative clue in case anyone’s interested

Cornflakes124 10.24.21 Reply

Block 2 Q38 (Q78 overall): Another clue is that the picture shows granulomas. If the stem indicates IBD and there is granuloma formation on histology, we know it’s Crohn’s disease. But ofcourse its much easier to recognize this by the skip lesions and fistula formation (punctuate hole was described in the question stem I think) – as already described by dr. White.
Thank you dr. White for the excellent explanations !!

Marvah 12.14.21 Reply

hi can u plz explain block 1 question 2: in 12 yr old girl with intermittent jaundice her total and direct bilirubin is high so it should be due to blockage of bilirubin secretion like dubin Johnson syndrome. how come the answer is gilbert?

Ben 12.14.21 Reply

The key with bili questions is which fraction predominates; you’ll often have a bit of both.
She has even more indirect bili than direct.

But I agree in this case they could have made things easier. Classic for Gilbert is total bili less than 5 with 20% or less direct.

Jay 01.04.22 Reply

Hi Dr. White,

I had a question about #58 (the herpetic whitlow one). My first impression was that the patient had hand, foot, and mouth disease so I picked RNA virus. How would I differentiate between herpes and hand, foot and mouth? Thanks for the explanations!

Ben 01.04.22 Reply

Well, the foot involvement for starters. And fever. Also the hand/foot lesions in HFMD are often more generically rashy red papules and not necessarily all vesicles.

Eunice 01.06.22 Reply

Thank you for this! Really appreciated it. :)

LEE 02.03.22 Reply

thank u so much. it was really helpful~~

Timothy Davis 02.12.22 Reply

(about question 114): “This question is garbage: wood dust is also a known carcinogen” Thank you, I was seriously beginning to doubt my sanity

Allison 03.25.22 Reply

Can anyone explain why the answer to 112 (Cushings syndrome) was not “C. Hypocalcemia and hyperglycemia”? I know pts with Cushings get insulin resistance and osteoporosis; does this osteoporosis occur in the setting of normocalcemia?

David 03.27.22 Reply

From my understanding osteoporosis has normal Ca2+ (as well as normal phosphate, normal alk phos, normal PTH – per the first aid table comparing osteoporosis vs. other bone disorders)

Court 04.09.22 Reply

Hahaha, I got a good chuckle at “brutal knock on Kentucky..” Thanks so much, this was extremely helpful!

K 05.02.22 Reply

so helpful god bless!!!!

CC 06.02.22 Reply

Thank you so much for the time and thoughtfulness you put into this. It was so helpful.

Jay 06.08.22 Reply

Hello! Thank you for these explanations!
Can you please post answer explanations for the new free120? I am taking my exam next tuesday :l

Ben 06.08.22 Reply

Sounds like they just updated the interactive set yesterday, but they haven’t gotten around to uploading the new PDF yet. I’ll probably be waiting until then, but even if it was available now I unfortunately probably wouldn’t be able to knock them out over the next few days.

Jay 06.10.22

LOL! Makes sense… It was worth a try

lily 06.12.22 Reply

are you going to be posting free120 2022?

Ben 06.13.22 Reply

When they get around to updating the PDF, yes.

Tesi 06.25.22 Reply

I took the free120 3 days ago and these are the exact questions! I don’t understand since I was supposed to be taking the ones for 2022?
Thank you so much for the explanations! Very helpful.

Ben 06.26.22 Reply

I’ve definitely noticed the individual centers are very variable in how fast they implement the free 120 updates.

Logan 08.26.22

?? When you say centers, what do you mean

Ben 08.26.22

Testing center.

Gagan 07.24.22 Reply

What do you think of using Uworld like Anki i never understood why people use Flash cards when they can just use questions?

Ben 07.30.22 Reply

Because flashcards are much, much faster for covering raw material and have the ability to incorporate a spacing algorithm to fight against the forgetting curve. Also useful, but not a replacement for questions.

Karin Ström 09.25.22 Reply

Hi! Thank you so much for these wonderful answers – concise, funny and supportive :) I’m a Swedish IMG taking USMLE Step 1 in 12 days, after many many months of preparation, and now I’m trying figure out the smartest way to use my last remaining study days. I went through all of Uworld, then did all the incorrect answers again (half the bank), then all 6 CBBSAS, and I am now 70% through UWorld, second round. I did the current free 120 a few days ago and then the one you answer in this post. Now I’m wondering if I should do as many of remaining Free 120 practise questions that I can muster, or continue with Uworld? Which type of questions do you think are most relevant at this stage? Thank you so much in advance and thanks again for an excellent blog.

Leave a Reply