Explanations for the 2020 Official Step 1 Practice Questions

Another year, another set of explanations. As always, the order here reflects that of the new PDF released in February 2020. The official practice material page subsequently reverted back to the 2019 version, but as you can see the 2020 link remains live. (If you’re taking this in 2021, then see those explanations for updated questions #24 and 53)

Last year’s 2019 set is available here, though it was almost entirely a repeat of the 2018 set explained here.

The asterisks (*) signifies a new question, of which there are 36.

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. A – Organophosphate pesticide poisoning stems from their function as cholinesterase inhibitors, which result in a build of acetylcholine and consequent muscarinic/nicotinic receptor overstimulation, which leads to the potpourri of symptoms. Atropine is anticholinergic and so can counteract these effects.*
  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 farmstuffs, 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 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.*

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


Austin 05.30.20 Reply

Looks like the explanation for #106 was accidentally put onto #109.
Thanks for your work and publishing a high quality resource without charge.

Ben 05.30.20 Reply

Ack thanks for letting me know. Not sure how I managed that. Fixed now.

E 06.06.20 Reply

For #72, isn’t a choristoma normal tissue in a abnormal location? How does that differ from expecting to find gastric mucosa in the intestine? Thank you!

Ben 06.06.20 Reply

A choristoma is a benign tumor.

Steph 06.12.20 Reply

Thank you so much for creating these explanations! We all greatly appreciate your time and effort. :)

Mle aspirant 06.13.20 Reply

For #06 isn’t atrophy a sign of lmn leison.?how is this ALS when no spasticity or hyper reflexia or rigidity is mentioned?although the picture does look like als …confusing,!

Ben 06.14.20 Reply

I suppose it could be another neurodegenerative condition since they were not very specific with the UMN components. But the fact that there are LMN signs like weakness and fasciculations would make the additional LMN sign of atrophy highly likely regardless of the underlying condition.

E 06.15.20 Reply

16 D. Parinaud syndrome. Conjugate vertical gaze palsy is due to superior colliculus compression.

Ben 06.15.20 Reply

Yes, though the upward gaze palsy component of Parinaud’s syndrome is from dysfunction of the vertical gaze center of the medial longitudinal fasciculus.

J 06.15.20 Reply

In #57 can you explain why it could NOT be Superoxide Dismutase?

Ben 06.16.20 Reply

Not a matter of “not” but a more a matter of “not the best answer.” Though CGD can result in fungal disease (e.g. aspergillosis), it does not commonly result in disseminated candida infections (and recurrent serious bacterial infections remain a common feature).

Prathik 10.25.20 Reply

Superoxide dismutase is the enzyme required to neutrlise the superoxide (ROS) formed to prevent cellular injury i.e acts as an antioxidant.
Deficiency of superoxide dismutase is seen in familial forms of ALS.
CGD is caused by deficiency of NADPH oxidase

J 07.12.20 Reply

54 – thiazide diuretic causing hypokalemia, but how to explain the anemia? (or is she not really that anemic?) hypotension is due to the diuretic?
71 – she is not that hypotensive. how could it be orthostatic hypotension. what is “eating orange slices” supposed to clue towards? (same as eating ice in iron-deficiency anemia)?
72 – how is this is Meckel’s diverticulitis if he’s an adult?

Ben 07.12.20 Reply

54. Who knows, doesn’t impact the correct answer. Most commonly just iron-deficiency in a menstruating female, though GI blood loss in alcoholics is common as well.

71. 85/50 standing improving to 110/70 supine with legs raised? That’s orthostatic. She feels better and starts eating, the orange slices are a fun detail.

72. Not just kids. Just much more common in kids. The description leaves no doubt.

Aaftab Sethi 08.16.20

why cant 71. be an electrolyte abnormality ?

Ben 08.17.20

She fulfills the literal definition of orthostatic hypotension. Why try to chase down something else?

Never just ask why not something else. No one ever said it “can’t be” the wrong answer. It’s single best answer. The incorrect answer doesn’t have to be *wrong* to not be the correct choice. She probably does have hyponatremia as a result of sweat/volume loss, but that doesn’t therefore imply that a low serum sodium is the best explanation of her hypotension. She just ran a marathon!

Aaftab Sethi 08.17.20

But doesnt orthostatic hypotension occurs due to autonomic dysregulation ? Will running a marathon cause an issue with the autonomic nervous system ?🤨

Ben 08.17.20

The most common cause of orthostatic hypotension is just dehydration. She’s dehydrated because she just ran a marathon. This is very, very common and doesn’t require any logical leaps. You’re way overthinking it. You don’t want or need to be defining the differential diagnosis of orthostatic hypotension. Your job is to *recognize* it here.

Aaftab Sethi 08.17.20

Got it !! Thanks ! Ws just trying to reason out how i missed such an easy question 😢

ethan 04.02.21

in the question stem, if i remember correctly, it asks about her fatigue AND muscle weakness. The diuretic seemed like a better choice, given the hypokalemia. Knowing a side effect of thiazides is to also increase blood glucose, it made me think more that the drug was causing side effects.

Ro 09.06.21 Reply

@Aaftab Sethi I will address why these are wrong for future test takers.

“why can’t 71. be an electrolyte abnormality ?”
This doesn’t account for the drop in blood pressure when standing. It would be constant otherwise.

“But doesn’t orthostatic hypotension occurs due to autonomic dysregulation? Will running a marathon cause an issue with the autonomic nervous system ?”
Yes, but that is why you look at the heartbeat. If it were autonomic, the heart rate wouldn’t increase in compensation to the drop in pressure. That’s why orthostatic is a better choice because there is an increase in heart rate.

Elliot 07.16.20 Reply

110. Doesn’t stroke volume decrease past 150 bpm due to less time for diastole?

Ben 07.16.20 Reply

SV falls with increasing HR beyond a point, but why would you assume that the final SV is lower than at rest? That’s an unsupported leap. Single best answer: you know the correct answer has to be correct.

Elliot again 07.17.20

Thank you kind sir!

Zach 08.05.20 Reply

Regarding Q116. I literally had a UWorld question the other day with an extremely similar premise (Classic CF symptoms only one allele detected by screen (and this was of 70 common alleles)). The answer there however, was that it was different gene. Just because you have one bad allele in a common screen doesn’t mean you don’t have two bad alleles with a different mutation. Therefore when I saw it again (and so soon) I jumped on “CFTR mutation is unrelated to the phenotype” assuming that was their cryptic way of hinting at a different, undetected mutation.

I think the gist UWorld wanted us to get was that we shouldn’t doubt the lab findings.

If you had to make the choice, which way would you lean on test day?

Ben 08.05.20 Reply

I would lean the way this question was written. I think in this case “CFTR mutation is unrelated to the phenotype” suggests that this mutation is clinically irrelevant to her CF despite being one of the most common mutations. That seems like a big stretch.

Zach 08.06.20

Fair enough. I suppose its better to follow the NBME’s lead anyway. Thank you for your prompt response and for putting together this whole explanation set, it was really helpful!

Ark 09.12.20 Reply

#53 Why PTH is high and Ca++ is low after ligation of that artery? What is the mechanism of these biochemical findings?

Ben 09.13.20 Reply

Hypoparathyroidism and hypocalcemia are usually transient after thyroidectomy and is the reason for parathyroid autotransplantation during many thyroid surgeries. Most commonly, this is directly related to parathyroid injury, low PTH, and subsequently low calcium.

I don’t know why they chose to show you elevated PTH, which is atypical–possibly just to mess with you because no matter what the answer choice is clear. Maybe it’s a typo. The timing isn’t exactly specified, such that they could either be trying to imply some hormonal spillage (I don’t think so) or trying to show gland recovery and attempted normalization of serum calcium. Low calcium and high PTH is typically what you see in secondary hyperparathyroidism in the setting of renal failure, which isn’t the case here.

Neye 01.04.21 Reply

Thanks for doing this. It is super helpful and straight to the point. For number 9, maybe use People Who Inject Drugs (PWID) or Intravenous Drug Users (IDU) instead of drug addicts since that has a negative connotation.

Ben 01.04.21 Reply


Ariel 08.22.22

Where can I find the PDF file for Questions for the “2020 Free 120”?

Ben 08.23.22

Linked in the first paragraph.

Paola 01.23.21 Reply

Thanks for doing this! Very helpful explanations.

Just had a question for #62. I realize now that this is classic presentation for von Willebrand’s disease (got tricked with normal PTT values and normal platelet aggregation studies). I am confused as to how platelet aggregation studies are reported as normal if the platelets are said to not aggregate with the ristocetin assay. How could this be? Is it because it’s platelet adhesion what’s abnormal and not aggregation?

Ben 01.23.21 Reply

The most common subtype of VWD is a quantitative defect, which is often mild/nearly clinically occult and can have normal laboratory testing. This is one of those questions where the labs are really there to exclude the other choices.

The cofactor assay uses patient’s plasma but not their own platelets (i.e. it’s a way to measure vWF and other plasma factors) as opposed to the function of the platelets themselves.

This may be of interest:

Paola 01.26.21

Very interesting. Thanks for your quick response, Doctor White!

amin 04.17.21

keep it simple, platelet aggregation is what they said, my guess is that the problem will be with platelet adhesion

Lael 02.02.21 Reply

Question regarding 31, doesn’t gene rearrangement of antibodies occur in the lymph node not the bone marrow? That is why I got caught on this questions. (Page 105 first aid 2019)

Shah 02.16.21 Reply

Thank you so much for this, incredibly helpful!
This link allows the questions to be taken exam style: https://orientation.nbme.org/Launch/USMLE/STPF1
Not sure what the deal is with if it’s allowed to be posted, but if so this may help some people

Ben 02.16.21 Reply

Yes the NBME has the online testing version for all of the Step exams on the practice material page of the official USMLE site. The question order is different than the PDF (and the PDF is what I can use each year to compare to prior years for seeing which questions are new.)

Shah 02.16.21 Reply

Sorry about that, didn’t realize it was that obviously found! Feel free to delete my comment. The order was spot on with the PDF/your answers when I just did it

JL 03.03.21 Reply

113. Why is the patient’s patella displaced superiorly?

Thank you for making this!

Ben 03.03.21 Reply

Good question; that is because patella alta is commonly associated with Osgood Schlatter.

pooja 03.07.21 Reply

Thank you for these!
For question 57, what did the neutrophil count and the delay in bactericidal activity against Staph A. signify?

Ben 03.08.21 Reply

Lots of neutrophils trying hard but failing to normally act against Staph due to decreased killing efficiency.

270+ 03.22.21 Reply

Regarding q37, she has chronic hypertension so her baroreceptors prob have already reset their set point. I’m thinking the correct reasoning might be that untreated hypertension can lead to heart failure which will then cause decreased firing of her baroreceptors. Either way, this is more of a rule out question though.

Rob 03.31.21 Reply

Regarding the aminoglycosides+penicillin question – I think one of the main reasons they are used together, specifically, is that beta lactams disrupt the cell wall and allow entry for the aminoglycosides.

Kay 04.17.21 Reply

Can you please explain/add the answer for #120? It is the one with the heart sounds. Thank you for your help!

Veronica Davis 04.19.21 Reply

I’m not Ben, but here is my rationale for #120: the heart sounds at the aortic, mitral, and tricuspid areas are normal (lub-dub). The sound at the pulmonic area (left 2nd intercostal space) is the tricky one. There is a physiologic split when the patient inhales (increased time between closure of the aortic valve and pulmonic valves), but the splitting decreases/goes away when he exhales. This is because when inhaling, there is decreased intrathoracic pressure, allowing increased venous return -> more blood flowing into the right atrium through the SVC/IVC, and thus increased right ventricle blood volume. Since this volume needs more time to be pumped through the pulmonary arteries, it takes longer to the pulmonic valve to close, thus “splitting” the S2 heart sound.

Asher 04.21.21 Reply

For Question 28, I had looked at alkaline phosphatase being technically in the normal range (25-100) as eliminating PTH secreting adenoma as a possibility. Wouldn’t elevated PTH stimulate osteoblasts and therefore increase ALP out of the normal range?

Ben 04.21.21 Reply

That is not how I would approach this question. From Wikipedia:
“Alkaline phosphatase levels are usually elevated in hyperparathyroidism. In primary hyperparathyroidism, levels may remain within the normal range, but this is inappropriately normal given the increased levels of plasma calcium.”

I don’t think I’ve ever seen a question rely on this relationship. As a general rule, a secondary lab (alk phos here) may support an interpretation but rarely completely eliminates one, so unless you had other data that better support a differing diagnosis, there is no reason to abandon the most likely explanation.

Billy Bob 04.22.21 Reply

71 – Continuous action of the leg muscles during the marathon squeezes the veins and provides venous return for the heart while she is running. Once she stops, this suddenly decreases venous return (still has vaso/venodilation of the legs due to large amounts of local metabolites in her muscle). Therefore, blood pools in the legs, decreasing preload -> near syncope.

Ben 04.23.21 Reply

(And presumably exacerbated by dehydration.)

AB 05.01.21 Reply

Do you happen to know why Block 1 Q2 labs that show elevated Dbili? Shouldn’t that be normal?

Ben 05.02.21 Reply

The key with bili questions is which fraction predominates; you’ll often have a bit of both.

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.

Baz 06.03.21 Reply

Do you happen to have an explanation to the new Block 1, Q#24 in the August 2020 PDF? It’s different than the Feb 2020 PDF, which is what I’m assuming your explanations are based on. But the current interactive free 120 block 1 Q24 does not match with your explanation (completely different vignette).

Natalie 06.04.21 Reply

I took the acute liver failure as decreased conjugation of bili since the liver normally does that

Jill 06.06.21 Reply

Could anyone comment on why the other answers for #112 are incorrect? Specifically C, because I thought that Cushings could increase osteoporosis and increase hepatic gluconeogenesis.

Ben 06.06.21 Reply

Osteoporosis, absolutely, but not a consistent significant effect on serum calcium.

Jay Zoellin 06.11.23

I actually think that C should be correct too. Steroids are used to prevet calcium absorption in the gut and can be sued to manage hypercalcemia. Hyperglycemia is obvious. https://www.uptodate.com/contents/treatment-of-hypercalcemia#:~:text=Glucocorticoids%20(eg%2C%20prednisone%20in%20a,by%20reducing%20intestinal%20calcium%20absorption.

Grace 06.07.21 Reply

Thank you so much for such helpful, clear, FUNNY explanations! Maybe it’s all the practice questions getting to my head but I burst out laughing at the explanation for #59 – “Brutal knock on Kentucky as a place where children play in and eat mud.”

Ben 06.08.21 Reply

You’re very welcome. As for the cause, let’s go with me being extremely clever.

Joe 06.16.21 Reply

Man, you rock. There were more than a few questions on this exam that completely befuddled me, and your explanations really helped me understand the answers.

As a student, I think it’s so cool that a currently practicing doc (with kids!) took some of his precious free time to turn around and help the students. Thanks for sharing your time and knowledge!

Ben 06.18.21 Reply


Mohsin Ali 07.29.21 Reply

Question 114
Answer should be Radon or saw dust?

Ben 07.29.21 Reply

The correct answer according to the NBME is Radon, and it’s pretty clear that’s what they’re going for in the stem. But in my opinion, it is not a good question.

Athena 08.24.21 Reply

Sawdust increases the risk for adenocarcinoma of nose and paranasal sinuses.

Radon is the second common cause of lung cancer after cigarette smoking.

Source: Amboss

Ben 08.24.21

Amboss is incomplete there. Sawdust increases the risk of both types of cancer, though more so nasopharyngeal carcinoma. And not every basement has radon. But yes, that is the point of the question.

Sofia 08.07.21 Reply

Hello! in #6 why can’t it be Glyburide? Sulfonylurea –> increased insulin release –> whatever is described in the case can be true

Ben 08.07.21 Reply

They are not describing the direct effects of insulin in this description, and more insulin is essentially what Glyburide provides.

Sofia 08.07.21

I see.. still hard for me to differentiate, maybe I’m just overthinking.
Thanks a lot for the reply!

Safa 04.20.22 Reply

#66 also carbamazepine and phenytoin induce of 24-Hydroxylase enzyme by CYP24A1. Thus it converts 25-OH D3 to 24-25-OH D3(inactive form) and ultimately decrease of 1-25-OH D3(active form). And it’s all about metabolism :)
I sincerely appreciate…

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