There is more to the USMLE than volume of knowledge, and you can take the test efficiently by

acknowledging outright the things your subconscious probably already knows. This is a somewhat
randomly chosen question from the official 2013 USMLE Step 1 information booklet:
A previously healthy 48-year-old man comes to the physician because of fever and cough for 2 days.
He attended a convention 10 days ago, and two of his friends who stayed in the same hotel have
similar symptoms. His temperature is 38.3C (101F), pulse is 76/min, respirations are 20/min, and
blood pressure is 130/70 mmHg. Crackles are heard over the right lung base. A chest x-ray shows a
patchy infiltrate in the right lower lobe. A Gram stain of sputum shows segmented neutrophils and
small gram-negative rods that stain poorly. A sputum culture grows opal-like colonies on yeast
extract. Which of the following is the most likely causal organism?
(A) Campylobacter jejuni
(B) Eikenella corrodens
(C) Legionella pneumophila
(D) Proteus mirabilis
(E) Pseudomonas aeruginosa
Once youve done enough Step questions, you will already know the most likely answer at the word
convention (its C). Not every question can come as a knee jerk reaction, but one key to Step
preparation is not just overall knowledge but rather pattern-recognition and memorization.
What separates the massive scores from the excellent scores boils down to intrinsic genius, testtaking voodoo, and tons of studying. The first you cant change; the third you have to do (and should
do efficiently). The second you need to be clever about (and doing questions is key). You can lay a
strong foundation by making questions like the one above comically easy. Knowing the key phrases
and patterns can allow you to literally feel the right answer even without having conscious
knowledge. If you can get in the head of the question writer and know the tip offs, you can often
make a reasonable guess even if you dont actually know the basic science details the question is
supposedly trying to test.

Rid Yourself of Your MCAT Bias

Start by acknowledging that the USMLE is different from the MCAT. Knowledge during the MCAT
is foundation that allows you to reason through a question in order to arrive at an answer. Knowledge
in the USMLE is frequently the answer itself. There is minimal critical thinking involved. The slight
exception is physiology, which requires knowing more complex relationships (this goes up; this and
that go down; the other thing stays the same), which can also be memorized (though it is more
cumbersome to memorize than to intuit). Most of the test however is the straightforward application
of memorization dressed in the clothing of painfully verbose question-writing and enough length to
exhaust your sympathetic reserves.

MCAT and USMLE scores do correlate (of course they do). Know, however, that there are people
who perform very poorly on the MCAT that end up with massive Step scores. This is because you
can brute force your way to a solid score with questions, while its very difficult to improve your
verbal subscore on the MCAT.

Use the Force

The test-taking skill itself comes into play only in knowing when theyre trying to play you for a
fool. Inexperienced test-takers will second-guess themselves out of the correct answer or hinge their
guesses on irrelevant clues. Good test-takers get in the head of the question writer. Another official
example:
A 24-year-old primigravid woman at 28 weeks gestation has had nagging headaches, a puffy looking
face, and swollen legs for the past week. Her blood pressure is 180/95 mm Hg; it was within normal
limits earlier in the pregnancy. Urinalysis shows a protein concentration of 0.6 g/dL. Which of the
following is the most likely diagnosis?
(A) Acute glomerulonephritis
(B) Congestive heart failure
(C) Eclampsia
(D) Nephrotic syndrome
(E) Preeclampsia
The answer is E. This is classic preeclampsia, and the question goes out of its way to list an almost
comical number of criteria. That said, its a question about a pregnant patient with a seemingly
pregnancy-related problem. Only two of the five choices is specific to pregnancy. Question writers
very rarely include totally extraneous details, so you should be looking for a pregnancy problem first
and foremost before believing the voice on your shoulder telling you that theyre trying to mislead
you. So, ask yourself: if you didnt know anything at all about the actual criteria, which answer
would you guess? You should be guessing E (C requires a seizure).
USMLE questions are single best answer. That doesnt mean the other answers are 100% wrong or
that they arent even reasonable. Theyre just not the best. People find elements in the stem that
support other choices, and these force them to reconsider their gut (and usually correct) feeling. Your
feelings (except for that miasma of anxiety) matter, so dont ignore them.
In the above question, edema supports CHF and nephrotic syndrome. Proteinuria supports GN, and if
it were of a larger amount, nephrotic syndrome. These answer choices having true elements doesnt
take away from the fact that preeclampsiaexplains all of them.

But even if you dont know anything, your goal when guessing is to narrow down answer choices.
Think about the body systems involved, the time courses, acquired versus congenital, viral vs
bacterial, drug reactions, any answer choices you do recognize that you know cant be it. Cross stuff
out.
One more from the official packet:
An 18-year-old female athlete reports easy fatigability and weakness. Physical examination shows no
abnormalities. Laboratory studies show:
Serum
Na+
141 mEq/L
Cl
85 mEq/L
K+
2.1 mEq/L
HCO3 35 mEq/L
Urine
Na+
K+

80 mEq/24 h
170 mEq/24 h

Which of the following is the most likely diagnosis?

(A) Aldosterone deficiency
(B) Anxiety reaction with hyperventilation
(C) Diabetic ketoacidosis
(D) Ingestion of anabolic steroids
(E) Surreptitious use of diuretics
Female athlete is a code word for eating disorder (the answer is E). If the question mentioned a
boxer, wrestler, or other sport with weigh-ins, ditto. Board questions reflect an extremely judgmental
worldview with heavy-handed generalizations about race, sex, and a wide variety of stereotypes.
African-American females in their 30-40s have sarcoidosis. If a woman takes oral contraceptive pills,
the question is nearly always implying that she doesnt use barrier protection and has contracted an
STD. People who have recently immigrated from another country with cough have tuberculosis. If
its a child who has recently immigrated, then they have a vaccine-preventable illness.
Often, in order to allow you to reasonably pick an obscure or rare illness with a set of non-specific
symptoms, these giveaways make sense. Sometimes they just make the question easier. Other times,
its a second-order question and simply knowing the diagnosis isnt enough anyway. But always look
for a questions internal clues to help you guess, give you the answer, or boost your confidence. You
cant learn every fact, and sometimes you dont have to. When picking facts to learn from a long list
of tidbits,pick the ones that help distinguish a diagnosis from other likely/related answer choices.

Dealing with irritating clinical science questions

Which of the following is the most appropriate next step in management?

Which of the following is the most appropriate next step in diagnosis?
These question styles can make you question yourself and frustrate you in times when you otherwise
could have sworn you knew the answer. Here are a couple of takeaways from the official Step 2 CK
information booklet:
In emergencies/unstable patients, your go to answer is whichever one prevents death or most
stabilizes the patient. So, in the trauma setting, follow your ABCs (where C essentially always
means fluid resuscitation). For example, if tension pneumothorax is a possibility, then needle
decompression must be performed without delay. Always follow an algorithmic approach with the
goal of stabilization and prevention of avoidable complications. The definitive management is
almost always available as an answer choice and usually must be avoided for this style of question.
In real life, many things happen simultaneously, but while studying, always think about which thing
is the most crucial to perform.
A 22-year-old man is brought to the emergency department 30 minutes after he sustained a gunshot
wound to the abdomen. His pulse is 120/min, respirations are 28/min, and blood pressure is 70/40
mm Hg. Breath sounds are normal on the right and decreased on the left. Abdominal examination
shows an entrance wound in the left upper quadrant at the midclavicular line below the left costal
margin. There is an exit wound laterally in the left axillary line at the 4th rib. Intravenous fluid
resuscitation is begun. Which of the following is the most appropriate next step in management?
(A) Upright x-ray of the chest
(B) CT scan of the chest
(C) Intubation and mechanical ventilation
(D) Peritoneal lavage
(E) Left tube thoracostomy
This gentleman has a GSW to the abdomen extending to the thorax with ipsilateral respiratory
compromise from a hemothorax. You may remember from your studying that all GSWs to the
abdomen will go for exploratory laparotomy. But first things first, he has earned himself a chest tube
(choice E). After all, B comes before C in ABC. Now, if he were stable after the tube is in, he might
get a CT before going to the OR (B). He will certainly be intubated for surgery (C). But never forget
your ABCs. Dont get excited. Even if exploratory laparotomy or thoracotomy were answer
choices, they would also be wrong.
When patients are stable, the next best step/most appropriate test is that which is most likely to
make the diagnosis (always know the test of choice, especially for imaging studies) or rule out a lesslikely but potentially life-threatening diagnosis. If the diagnosis is already made, treat the problem

(there may be two treatments, but one is more important). Other tests may be reasonable and
performed concurrently in real life, but there is typically one test that is geared towards the most
likely diagnosis based on presentation. Thats the one you want. You should have some knee-jerk
associations for complaints (e.g. LLQ pain and fever diverticulitis CT scan of abdomen with
contrast; RUQ pain and fever cholecystitis RUQ abdominal sonogram). When given a classic but
non-acute disease presentation, always think about how to prevent catastrophic consequences.
42-year-old woman comes to the physician because of a 1-year history of vaginal bleeding for 2 to 5
days every 2 weeks. The flow varies from light to heavy with passage of clots. Menses previously
occurred at regular 25- to 29-day intervals and lasted for 5 days with normal flow. She has no history
of serious illness and takes no medications. She is sexually active with one male partner, and they use
condoms inconsistently. Her mother died of colon cancer, and her maternal grandmother died of
breast cancer. She is 163 cm (5 ft 4 in) tall and weighs 77 kg (170 lb); BMI is 29 kg/m2. Her
temperature is 36.6C (97.8F), pulse is 90/min, respirations are 12/min, and blood pressure is
100/60 mm Hg. The uterus is normal sized. The ovaries cannot be palpated. The remainder of the
examination shows no abnormalities. Test of the stool for occult blood is negative. Which of the
following is the most appropriate next step in diagnosis?
(A) Barium enema
(B) Progesterone challenge test
(C) Colposcopy
(D) Cystoscopy
(E) Endometrial biopsy
Now, there is a rule about abnormal vaginal bleeding in women over 35, but lets say you didnt
know that. Ask yourself, what would be the worst thing to cause non-acute bleeding? What would
you want to rule out? Cancer. Could it be that she has amenorrhea and that a progesterone challenge
test could answer our question? Yes. But we must rule out the life-threatening cause. The answer is E.
So

Stabilize if necessary ABCs, even for non-trauma patients

Diagnose if necessary Test of choice to make the diagnosis or the test that will rule out a
potentially life-threatening cause

Treat If there are multiple appropriate options, which one is the most crucial?

Ultimately, most questions are fair. That said, every once in a while, the question is actually terrible.
If after all is said and done, it makes no sense, dont extrapolate too much from it for your general
test taking skills.

Managing Anxiety
There are always miserably hard questions on NBME Shelf and USMLE Step exams, and thats
okay. Its not realistically possible to get them all right. The nature of the test is such that a ball of
doubt will form deep in the core of you body, growing with each question you waver on. And, the
test is designed to make you waver over that second answer choice which doesnt feel right (but you
cant explain why its wrong). Allow yourself to approach the tests with an air of dispassion and
nonchalance. Your nerves dont help you. Your instincts do.
Stay awake. Stay focused. Use what they give you to make your life easier. When you dont know an
answer, try to narrow it down based on internal characteristics, guess, and move on. If you go back to
change an answer, you must know why and have a good reason. Never change an answer arbitrarily
because of feelings.

Block 1
1.

C Acute abdominal pain in a fertile woman is very frequently going to be an ectopic

question. Associated fun fact: the most common cause of secondary amenorrhea is pregnancy.

2.

E Parents can be overly protective of their children with chronic diseases (diabetes, lupus,
etc). This child doesnt have SCID, so going to school isnt going to kill them. The child is an
overall reasonable health with only mild symptoms. Vulnerable child syndrome is characterized
by unreasonable parental anxiety. *

3.

B HGPRT = high uric acid. Self-mutilating behavior (e.g. bad finger biting) is one of the
more specific clinical features.

4.

E Functional parathyroid adenomas can cause elevated parathyroid hormone (PTH), which
results in hypercalcemia and hypophosphatemia. Hypercalcemia is characterized by the rhyming
symptoms of: 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). *

5.

B You are seeing a tube inside of a tube in the pathology specimen. Yes, look again: bowel
within bowel. Intussusception. Currant jelly stools. Classic history (sudden onset colicky pain,
palpable mass). Now, a right lower quadrant lesion that causes pain and hematochezia,
particularly in a child? Then you would get to think of Meckels (with its rule of 2s).

6.

F While staph aureus is the most common cause of hematogenous osteomyelitis in children,
Salmonella is the most frequent cause for patients with sickle cell anemia (a test favorite). I think
I may have even had this fact tested twice on my Step.

7.

D Reyes syndrome is the reason why children dont receive aspirin (except to treat
Kawasakis disease, of course). Reyes syndrome is characterized by vomiting followed liver
damage (hepatic steatosis and hepatomegaly) and encephalopathy beginning with irritability and
aggressive behavior and potentially progressing to coma.*

8.

B Bisphosphonates work by decreasing osteoclast activity (thereby reducing bone

resorption). Choice is F is the opposite of how estrogen therapy works (RANKL is found on
osteoblasts, and its activation triggers osteoclasts and stimulates bone resorption).*

9.

B Azotemia, hemoconcentration, and hypotension/tachycardia are all results of

dehydration. This may lead to acute renal failure if allowed to continue (but this diagnosis
requires a change in creatinine of 0.3).

10.

A Phenylephrine is an alpha-agonist nasal spray and oral medication that often shows up on
exams. Oxymetazoline (Afrin) is a similar alpha-agonist nasal spray. Pseudoephedrine is another
decongestant with a similar MOA thats less common now that its a federally monitored
component of methamphetamine production. Topical alpha agonist decongestants are physically
addictive and can cause miserable rebound congestion (rhinitis medicamentosa). Systemic
formulations can cause hypertension and worsen prostate problems by causing prostatic smooth
muscle constriction. Just remember that tamsolusin (Flomax) is an alpha-5a antagonist, which
relaxes prostate muscle.

11.

A She has nephrogenic diabetes insipidus (large volume dilute urine production that cannot
be reversed with the administration of exogenous vasopressin). Aquaporins are the water
channels that allow for the reabsorption of free water from the collecting ducts and the
production of concentrated urine.

12.

A The p-value corresponds to the likelihood of a type I error (a false positive). A lower pvalue 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).*

13.

A Gonorrhea can change its pillus, which is responsible for adhesion to host cells and the
main antigen to which the host mounts an immune response.Neisseria gonorrhoeae is able
switch out different pilin genes, and for this reason, prior infection does not confer long lasting
immunity.*

14.

B Crossed findings (upper motor neuron on one side, lower motor neuron on the other)
means a brainstem lesion. Left (ipsilateral) tongue, right-sided (contralateral) weakness means
the exiting left hypoglossal nerve has been affected (within the left medulla). B is in the pyramid
where the corticospinal tract runs to control muscles (prior to the decussation).

15.

A p53 is the quintessential tumor suppressor (it activate apoptosis). Carcinogenesis of HPV
is caused by insertion of the virus into the host DNA and producing a protein which binds with
an essential p53 substrate, functionally inactivating the p53 and its apoptotic cascade. C
(transactivation/TAX) is how HIV and HTLV cause cancer. E (cmyc translocation) causes Burkitt
lymphoma.*

16.

A Atypical antipsychotics (e.g. clozapine, quetiapine, etc) are more likely to improve
negative symptoms (affective flattening, anhedonia, avolition, aphasia) when compared to typical
antipsychotics (e.g. haloperidol). They are no more effective at treating positive symptoms
(hallucinations, delusions). Highly testable fact.*

17.

A Its the antibodies to surface antigens that are protective. Hemagglutinin is a surface
antigen that is responsible for clumping RBCs in vitro.

18.

A All the vesicles contain the same viral infection, so all should have the same appearance
on gel. Choice D is what a gel looks like without using a restriction enzyme digest (no discrete
bands of specific weights).

19.

E Xanthogranulomatous pyelonephritis (XGP) is a rare form of chronic pyelonephritis,

especially associated with Proteus infection. Tumor-like growth, upper urinary tract infection,
and (this is key) lipid-laden foamy macrophages make this neither acute pyelo nor cancer.
Malacoplakia causes GU papules/ulcers, typically of the bladder (not super important).

20.

B Post-streptococcal glomerulonephritis is caused by the deposition of circulating immune

complexes (a type III hypersensitivity and a test-favorite).*

21.

A As always, its 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 and particularly urease, which allow it to decrease the pH of the 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.*

22.

D Schistosomiasis is a parasitic worm particularly endemic in Africa (Egypt in particular

comes up a lot 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).*
23.

E This patient has chronic kidney disease, as indicated by elevated serum creatinine/BUN
and evidence of anemia of chronic disease (normochromic normocytic). Poorly functioning
kidneys do not hydroxylate 25-Dihydroxycholecalciferol to 1,25-Dihydroxycholecalciferol well
nor produce adequate erythropoietin (hence the CKD-related anemia). Patients with CKD
development thus develop secondary hyperparathyroidism due derangements in phosphate
excretion and inadequate Vitamin D activation resulting in hypocalcemia. Thus, we should
expect to see low calcium, high phosphorus, low 1,25 vitamin D, and low Epo, which is E.*

24.

C Isoniazid can cause peripheral neuropathy due to its depletion of pyridoxine (vitamin
B6). B6 supplementation is therefore preventative. INH can also cause drug-induced lupus
(another test favorite) and sometimes severe liver disease (also fair game).*

25.

C The meningitis diagnosis is a giveaway. Your job is to know two things: 1) the common
pathologic organisms in different age groups or 2) that Neisseria is a gram negative diplococcus.

26.

B To amplify tiny fragments of DNA in order to detect their presence, we use PCR. The
question is a description of the process. Southern Blots are used to detect a specific DNA
sequence within a DNA sample.*

27.

C Hookworm infection can cause intestinal irritation leading to chronic GI blood loss and
iron deficiency anemia. An otherwise healthy boy who lives in rural Mississippi, probably
playing in the mud in his bare feet like a hillbilly? Thats the kind of kid who would get
hookworm. Treatment is mebendazole (albendazole would also be fine. These are your go to
choices for anti-helminthics).*

28.

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).*

29.

D You need to memorize the list of drugs that induce and inhibit CYP450. Warfarin has
oodles and oodles of drug reactions for this reason with potentially dire consequences.

30.

C Leydig cells make testosterone. Leydig cell tumors arent always physiological active,
but those that are can cause masculinization. Granulosa cell tumors, on the other hand,
sometimes produce estrogen. 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.*

31.

B This patient has cystic fibrosis. The combination of respiratory and GI issues is classic
and caused by ineffective chloride transport and consequently thick exocrine secretions, which
clog up the airways and the pancreatic ducts.

32.

E Polycythemia Vera is the red blood cell cancer. Symptoms are related to hyperviscosity of
the increased hematocrit. A classic symptom of polycythemia vera is pruritus, typically with
exposure to hot water (e.g. the shower). Super high hematocrits are indicative. Low EPO means
that the body is responding appropriate by trying to tone down RBC production (which continues
autonomously in PCV). JAK2 mutation, test favorite. The classic treatment is bloodletting, like
they used to do for everything back in the middle ages.*

33.

D Sensitivity rules things out. Its TP / (TP + FN). So in order to calculate the sensitivity of
this test, we need the true positives (the 90 with cancer) and the false negatives: the patients for
whom the test is negative but actually do have prostate cancer. Thats D.*

34.

C Polyarteritis nodosa is that only one that makes sense in explaining the diffuse
constellation of symptoms in this question. It affects small and medium arteries, including those
involving the skin, heart, kidneys, GI tract, etc. On imaging, a rosary sign of small aneurysms
strung like beads on a rosary is sometimes mentioned. The biopsy shows an inflamed artery
(arteritis). Angiodysplasia typically causes painless GI bleeding (like that seen in diverticulosis).
Kawasaki disease is in children (5 days of fever, strawberry tongue, etc). Takayasu arteritis
involves big arteries, like the aorta, carotids, and subclavians (with classically diminished upper
extremities pulses, hence pulseless disease). Thromboangiitis obliterans is also known as
Buergers disease, a vasculitis seen essentially exclusively in smokers that causes severe
peripheral arterial disease (legs much more so than hands). Wegeners is typified by the
combination of renal and lung (and sinus) findings in conjunction. The picture would should
granulomas, and C-ANCA would likely be positive, because its a board exam.*

35.

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).*

36.

B Six-year-olds typically understand the finality of death. Infants have no understanding,

whereas preschool age children often think of deaths in reversible or metaphorical terms.

37.

B Thiazides (typically used an antihypertensives) also increase calcium resorption in the

distal tubule and are therefore useful in preventing calcium oxalate stone formation in patients
with hypercalciuria (the mechanism is not really worth learning). Thiazides block the Na-Cl
symporter, as opposed to loop diuretics, which block the triporter, and acetazolamide, which
blocks carbonic anhydrase in the proximal tubule.*

38.

A Pyknosis and nuclear fragmentation are part of the process of apoptosis.

39.

A Acetaminophen (Tylenol) can cause fulminant hepatic failure in overdose. This will
probably be on your test.

40.

A The infraspinatus and teres minor are responsible for external rotation. Both the
infraspinatus and supraspinatus muscles are innervated by a suprascapular nerve.*

41.

B Osteogenesis imperfecta (blue sclera, lots of fractures [they even occur prenatally]) is a
defect in type 1 collagen.

42.

C Filgrastim is a granulocyte colony stimulating factor, which are drugs use to increase
white blood cell count in patients with leukopenia. Leucovorin (folinic acid) sounds like it would
also be right; its used to prevent bone marrow suppression in patients taking methotrexate.
Darbepoetin (like erythropoietin) is used to stimulate red blood cell production.*

43.

F A Nystatin mouthwash is the treatment of choice for oral candidiasis. Its topical, its
easy, it works. For tongue thrush, the patient can spit it out (and therefore no chance for side
effects). For pharyngeal/esophageal candidiasis, the patient can swish and swallow. Inhaled
cortisteroids, particularly if used without an air chamber (spacer) can cause local immune
suppression when contacting the oral mucosa, leading to thrush.*

44.

A Turner syndrome (you may remember lymphedema of the neck by another name: cystic
hygroma). The 45,X gives it away though anyway. Mosaic Turners syndrome and the mosaic
trisomies result from nondisjunction during mitosis. In total monosomy/trisomies, the cause is
nondisjunction during meiosis. Uniparental disomy is essentially only tested via the Prader-Willi
and Angelman syndromes (chromosome 15).

45.

C GVHD sucks. Skin and GI lesions are especially common sites (mucosal tissues are
rapidly dividing and thus prone to attack).

46.

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 theyre dehydrated).
Likewise, systemic capillaries will prefer to hold onto plasma and not let it leak into the
interstitium (third-spacing).*

Block 2
47.

C Home canned/bottled food is a buzz-term for botulism. Thats also why the bottles you
buy in the store have that little pop up lid that stick out when you open it. If theres botulism
forming air in the bottle, then the lid pops up (and you shouldnt eat it!). Botulinum toxin inhibits
the release of acetylcholine (which actives the nicotinic receptors necessary for skeletal muscle
contraction).*

48.

C Blood flow also increases during exercise. The more anaerobic metabolism you use and
lactate build-up you have, the more hyperemia you need to clear out the waste products.

49.

B Aminoglycoside antibiotics (gentamycin, amikacin, etc) are powerful antibiotics

especially useful for bad gram negative infections. Bad side effects are permanent hearing loss
(ototoxicity) and renal failure. Both are important to know. Torsades de Pointes (choice E) can be
caused by fluoroquinolones (e.g. cipro), as these drugs prolong the QT-interval.

50.

B Memorize aspirins acid-base effects: metabolic acidosis and respiratory alkalosis. Note,
this is actual respiratory alkalosis, not simply normal respiratory compensation for metabolic
acidosis.

51.

C This patient has hepatitis (elevated liver enzymes) due to active Hepatitis C infection.
Hep C and HIV infection are both associated with intravenous drug use. While most patients
with Hep A will clear the virus after their acute illness, Hep C causes chronic infection in 80% of
patients, which may lead to cirrhosis over time (~20 years).*

52.

C Osgood-Schlatter is also known as apophysitis of the tibial tubercle. Its due to chronic
stress/irritation at the insertion of the patellar ligament on the tibial tubercle. Its classically seen
in the teenagers doing repetitive vigorous activity (running, jumping). The radiograph
demonstrates classic fragmentation of the tibial tubercle (which isnt necessary to know to get the
question correct).*

53.

E Gram positive rods in a diabetic foot wound (or a World War I soldier fighting in a
trench) means Clostridium perfringens (the causative organism of gas gangrene). Crepitance
means gas in the tissues, which is produced as a byproduct of its highly virulent alpha toxin.*

54.

D Those are varicose veins, and theyve described symptomatic varicosities. Incompetent
valves allow reflux of blood into the dependent feet and legs. The pooling blood increases
hydrostatic pressure, causing edema.

55.

A Electrical alternans on boards means a big pericardial effusion (and usually cardiac
tamponade). The heart cannot fill properly, preload decreases, hypotension and tachycardia
ensue, fluid backup leads to elevated JVP.*

56.

D Antibiotic-associated diarrhea caused by clostridium difficile can be tenacious, difficult

to treat, and even fatal. Alcohol-based rubs are not sufficient to kill the spores. Handwashing
with soap is necessary, and equipment should be autoclaved to clean it.

57.

A Ballet dancers (wrestlers, models, ballet dancers, athletes who need to make weight, and
particularly young women in general) all have eating disorders on Step 1. Folic acid is involved
in the production of both red and white blood cells. Remember, low folate leads to macrocytic
anemia and hypersegmented neutrophils. B12 deficiency (not an answer choice) leads to
macrocytic anemia and neurological changes (including SCID in severe cases).

58.

D ITP causes immune-mediated consumption of platelets, hence the low platelet count and
petechiae. The bone marrow biopsy results demonstrate that the body has appropriately increased
platelet production, meaning that this is not a platelet production issue. While TTP has a similar

acronym, its an entirely different disease with a classic pentad: thrombocytopenia (low platelet
count), microangiopathic hemolytic anemia, altered mental status, renal failure, and fever.
59.

G Vincristine (a mitosis inhibitor) frequently causes peripheral neuropathy, which can be

severe and irreversible. Other fun associations are Bleomycin with pulmonary fibrosis,
Cyclophosphamide and bladder cancer, and Doxorubicin with dilated cardiomyopathy.*

60.

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.*

61.

D People in their 60s dont spontaneously become schizophrenic with any frequency for
that to be ever be the correct answer. Likewise, Alzheimers is a slowly progressive cognitive
decline (dementia), not an acute decline in mental status (i.e. delirium). This patient is delirious.
Common causes in the elderly includes medications, infections, and being in the hospital
(particularly the ICU).*

62.

C Anaphylaxis is treated with epinephrine.

63.

C Logic would dictate that a fracture of the inferior orbital wall might affect the infraorbital
artery, and logic would be right.*

64.

C If you know you are getting a drug, then you are not blinded: its an open label trial. It is
a clinical trial though.*

65.

C Ah, you really want to pick A for cat scratch fever. But sore throat, adenopathy,
and a positive Heterophile antibody test means mononucleosis (i.e. Mono), caused by EpsteinBarr Virus. The heterophile antibody test is due to a cross reaction with horse or sheep red blood
cells, which are agglutinated in vitro by the antibodies in the patients serum.*

66.

C RSV, like all respiratory viruses, spreads via respiratory droplet. Babies are too young to
wheeze because of asthma; they wheeze because of RSV.

67.

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.*

68.

D Recurrent respiratory infections could be a lot of things. But then they mention the
dextrocardia. Kartagener syndrome is the combination of situs inversus and defective cilia (due
to a mutation in dynein), where the inability to effectively clear secretions results in recurrent
sinusitis and bronchiectasis.

69.

B Choriocarcinoma is a much-feared complication of a molar pregnancy. It is a cancer of

the bHCG-producing syncytiotrophoblasts found in the placenta.

70.

D The suprachiasmatic nucleus of the hypothalamus controls circadian rhythms. A few

more key thalamic nuclei are worth knowing: Supraoptic releases vasopressin (ADH). The lateral
nucleus controls thirst and hunger. The ventromedial controls satiety. Anterior controls
temperature. The paraventricular nucleus releases CRH, TRH, and oxytocin.

71.

B This patient has symptomatic anemia. Its microcytic nature implies iron deficiency,
which is most commonly due to occult blood loss. In the elderly, the concern is colon cancer. In
a reproductive age female, iron deficiency is more commonly secondary to uterine pathology.

72.

C Factor V leiden is by far the most common heritable cause of hypercoagulability. Keep in
mind that many most likely questions are actually asking you for the most common cause.*

73.

D This is rheumatic fever from group A strep pharyngitis. This is thankfully rare now, as
we routinely treat Step throat with antibiotics. The cause of all the damage is due to crossreactivity of Strep antigens with the tissues of the heart, joints, skin, and brain. Anti-streptolysin
O (ASO) and anti-DNase titers will be high.

74.

D The Odds Ratio (OR), if you dont simply have it memorized, is computed exactly as you
would guess. Its the odds of you getting a disease with the treatment (or risk factor) over the
odds of you getting a disease without the treatment. In this case: 100/200 divided by 300/300 =
1/2.*

75.

D Rickets. Pectus carinatum is also known as pigeon chest (protruding sternum) and
bead-like enlargement of the costochondral junctions is describing a rachitic rosary. Rickets is
caused by vitamin D deficiency (either dietary or functional). Osteoblasts in patients with rickets
lay down excess unmineralized osteoid, as they are less able to mineralize osteoid into mature
bone without sufficient vitamin D.*

76.

C Lymphatic spread of disease moves through lymphatic channels from distal to proximal.
Just follow logic. In the lower extremity, thats foot to knee to groin.

77.

G Sulfonylurea medications (glipizide, glyburide) stimulate the pancreas to secrete more

insulin. For this reason, they are most efficacious early in the disease process when pancreas still
has remaining functional reserve.

78.

E Those are sickle cells on the smear. LUQ pain on test questions almost always means
splenic pathology. All sickle cell kids will eventually infarct their spleen.

79.

E Subacute combined degeneration (progressive peripheral sensory and motor loss) is a late
sign of B12 deficiency, which is common in old people. On board 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.

80.

D An OR greater than 1 signifies increases odds/risk/likelihood. If the 95% CI range does

not include 1, then the difference is statistically significant (though not necessarily clinically
meaningful).*

81.

C Common sense is key, particularly for counseling-type questions. Patients have

autonomy and can do whatever they want; its your job to explain the risks and benefits. The
patients ultimately make their own treatment choices.

82.

D She is taking anabolic (androgenic) steroids as a performance enhancing drug. Being an

athlete on Step 1 is never a good thing.*

83.

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 be 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.*

84.

B This is a (prospective) case series. There is no control (and certainly no blinding).*

85.

D Pregnant patients should avoid fish and seafood products that are high in mercury. In
general, this means that shellfish and big salt-water fish should be avoided (tuna, swordfish,
shark, king mackerel, tilefish, etc)*

86.

A Air and fluid = hydropneumothorax. If that fluid is blood (s/p stabbing), its a
hemopneumothorax. Lack of mediastinal shift indicates that its not under tension.*

87.

C Middle-aged woman with progressive shortness of breath? Think of idiopathic

pulmonary fibrosis, a restrictive lung disease.

88.

B Finasteride (aka Propecia) is used for male pattern baldness and prostate hypertrophy. Its
a 5-alpha-reductase inhibitor, which prevents the conversion of testosterone to
dihydrotestosterone (DHT).

89.

B Gout, gout, gout. Allopurinol helps prevent flares but does nothing to treat them.
Treatments of choice for an acute flare are NSAIDS or colchicine.

90.

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, its all or nothing.*

91.

F Prolonged bleeding time with normal clotting factors (as evidenced by normal PT/INR
and PTT) and a sufficient platelet count is going to be von Willebrand disease, the most common
hereditary coagulation abnormality, which by either deficiency or mutation results in
dysfunctional platelets. A temporary treatment for uncontrolled bleeding is vasopressin, which
causes for addition vWf release. Factor VIII concentrate is a more dramatic and more effective
treatment, as it also contains vWf.*

92.

D Diffuse low-level ST elevation means pericarditis. These patients often complain of

pleuritic chest pain, which is somewhat alleviated by sitting up and leaning forward, and have
distant heart sounds. Common test causes include viruses, uremia, and 2-3 weeks after
myocardial infarction (Dressler syndrome). *

Block 3

93.

E Profuse super-watery diarrhea means cholera (the so-called rice water stool). That said,
regardless of the cause, you treat all causes of volume loss with volume replacement (normal
saline)!

94.

D Torticollis is a type of focal dystonia, which is a type of EPS (extrapyramidal symptoms)

caused by neuroleptics (antipsychotics), such as haloperidol. Uncontrollable facial grimacing is a
description of tardive dyskinesia, a rarer sometimes permanent EPS more associated with longterm antipsychotic use.*

95.

C Thats a litany of symptoms with only one reasonable single possible cause out of the
provided choices: hyperthyroidism. Elevated thyroid hormone can manifest as anxiety, GI
hypermotility, tachycardia and a-fib, weight loss, heat intolerance, etc. Thyroid disorders are very
high yield. Pheochromocytomas (choice E) can cause some of the same symptoms in
an episodic fashion (more typically panic attacks, episodic severe hypertension, headache).

96.

A Narcotic use for acutely painful conditions is both reasonable and important. Short-term
use (immediately post-surgical) does not lead to long term dependence. And yes, drugs addicts
should also receive narcotics to control pain.*

97.

E The most important cause of papillary necrosis is analgesia [abuse] nephropathy, a type
of kidney damage caused by long-term use of OTC pain medications. Ischemia from disruption
of blood flow from the vasa recta causes necrosis and sloughing of the renal papilla. Hematuria
and sterile pyuria are common.*

98.

A Altitude sickness can cause high-altitude pulmonary edema (a type of ARDS). The x-ray
demonstrates diffuse bilateral fluffy infiltrates.*

99.

A The genetic questions always seem to hinge on remembering (or deducing) that T in
DNA is replaced by U in RNA.*

100.

B If you think about this logically, what we have here is a congenital intolerance to

breastmilk: 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.*

101.

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.*
102.

E Ventricular fibrillation is the most common cause of sudden cardiac death immediately

after myocardial infarction. This is why we have AEDs all over the place now. Papillary muscle
rupture classically occurs 2-7 days after an MI and results in massive life-threatening mitral
regurgitation. Free ventricular wall rupture after an MI can result in cardiac tamponade. *
103.

E PPIs raise pH by preventing the normal secretion of HCl into the stomach by parietal

cells. The body attempts to counteract this unnaturally basic gastric pH with compensatory
hypertrophy. If our medications are moving a measured element beyond its set-point, the body
nearly always tries to compensate.*
104.

E The whole afferent/efferent thing is worth knowing. When the efferent arteriole is

independently constricted, the blood can get into the glomerulus but has difficulty getting out. So
more blood spends a greater amount of time in the glomerulus being filtered: GFR up, filtration
fraction up, but overall blood flow is decreased due to the increased resistance of the system as a
whole.
105.

A Benzodiazepines (including alprazolam aka Xanax) are effective at treating anxiety

conditions. Ideally, their use should be limited to bridge therapy awaiting the efficacy of safer
less habit-forming maintenance medications like SSRIs and buspirone.*
106.

C If you dont eat enough calories to run your metabolism, your body will mobilize its

stores. We burn fat through fatty acid oxidation.

107.

E Chronic microcytic anemia in a patient with normal iron studies should make you think

of thalassemia. -Thalassemia minor is the most common and is typically quite mild. As there is
decreased beta chain production, there is a relative excess of alpha chains.*
108.

E Tetracycline use during childhood is commonly associated with tooth discoloration,

typically yellow-brown (sometimes described as gray).*

109.

A Targetoid rash after a woodland excursion means lyme disease, caused by Borrelia

burgdorferi, carried by the Ixodes tick. Rash (erythema migrans), viral syndrome symptoms,
fatigue, and poly-arthritis are common. Lyme carditis typically manifests as AV block.*

110.

A Adalimumab is the only TNF inhibitor on the list. The fancy targeted therapies are all

monoclonal antibodies and thus end in ab.*

111.

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.*
112.

C AIDS retinitis is caused by CMV (typically seen with CD4 count less than 50). Treatment

is with ganciclovir.*
113.

E This patient has stress incontinence, a common complaint in women after vaginal

childbirth, the risk of which increases with number of deliveries, the size of the baby, and use of
forceps, etc. The pelvic floor muscles and urogenital diaphragm are innervated primarily by the
S3-4 nerve roots.*
114.

A Chronic anovulation is a common cause of infertility. Long periods are often anovulatory,

where lack of an LH surge leads to unchecked estrogen and prevents ovulation and the secretory
and menstrual phases that follow, leading to chronic proliferative-phase endometrium and
irregular menses, which can be long or short, often light (as only the endometrial tissue that
outgrows its blood supply sloughs off).*
115.

A GBS comes from a mothers colonized vagina and is the most common cause of neonatal

sepsis. Women who are GBS+ should receive PCN prophylaxis prior to delivery to prevent
exposure to the fetus during delivery.*
116.

B Psychogenic polydipsia (PPD) is associated with several psychiatric conditions,

particularly schizophrenia. It is also sometimes felt to be secondary to the dry/cotton mouth seen
with certain medications, including antipsychotics. Patients present with hyponatremia due to
their excessive free water intake. In some cases, a water deprivation test is necessary to
distinguish PPD from diabetes insipidus.*
117.

A Foot drop after compression in the lower leg = common fibular/peroneal nerve. Nerve

compression syndrome = one reason why its important that casts not be too tight.*
118.

A The closer R is to 1, the more closely the data points should fit to a line. I think the

NBME is trying to imply that I will have poorly controlled diabetes in the future.*

119.

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.*
120.

C In this question, they have described the components of congenital rubella. The

distributed purpura (a result of extramedullary hematopoiesis) is a description of the classic

blueberry muffin rash (which you are highly unlikely to hear actually described as such on a
test).*
121.

B Fatigable weakness, particularly of the eyes, is classic myasthenia gravis, an autoimmune

condition cause by antibodies that block acetylcholine receptors at the postsynaptic

neuromuscular junction. The arrow is pointing to the patients prominent thymus. Thymoma and
thymic hyperplasia are both in common in the patients with MG, and thymectomy is curative in a
portion of patients. Small cell carcinoma of the lung is associated with Lambert-Eaton
myasthenic syndrome, a disease caused by autoantibodies against presynaptic calcium channels.
These patients classically begin weak and an experience a warm up effect after some use (they
ultimately become weak again though).*
122.

A Renal artery stenosis causes decreased blood flow to the supplied kidney, which results in

the activation of the Renin-Angiotensin-Aldosterone System, because the hypoperfused kidney

secretes renin from the juxtaglomerular cells. The normal kidney has normal renin secretion.
However, the additional circulating aldosterone will cause the normal kidney to retain
sodium/water.*
123.

E Tons of exercise followed by renal failure is always going to be rhabdomyolysis. Dark

urine (without actual blood in it) is due to myoglobinuria, which can cause a false positive urine
dipstick.
124.

A In additional to thyroid problems, amiodarone can cause interstitial lung disease,

including potentially fatal non-reversible pulmonary fibrosis. Digoxin is famous for its narrow
therapeutic range and numerous side effects, including green-yellow vision changes. Lisinopril
can cause angioedema, as well as hyperkalemia. Metoprolol can exacerbate asthma in addition to
causing dizziness, bradycardia, and hypotension. Procainamide can cause drug-induced lupus.*

125.

E Delayed separation of the umbilical stump is a classic clue for leukocyte adhesion

deficiency. ICAM is the defective ligand most often asked about as a second order question.
126.

A This patient has Conns syndrome (primary hyperaldosteronism), most commonly caused

by a hyperfunctioning adrenal adenoma. This is an important and highly tested cause of

refractory hypertension. The patient has lab abnormalities consistent with high aldosterone (high
sodium, low potassium, metabolic alkalosis) with an appropriately suppressed renin.*
127.

E A chronic heaped up ulcerative lesion of the skin, especially on sun-exposed areas in

people who spend time outdoors, means cancer. If its keratinocytes at play (and not
melanocytes), that leaves you with either squamous cell or basal cell carcinoma.
128.

B Alcoholics (and any person with an altered level of consciousness) are a set-up for

aspiration pneumonia: classically RLL, classically foul-smelling. The organism on tests will be
Klebsiella.
129.

D Cholesterol xanthomas, horrible serum cholesterol levels, and early death by MI are all

signs of familial hypercholesterolemia (caused by a defect in the LDL receptor).

130.

E All of the congenital heart defects and their associated murmurs are high-yield and worth

memorizing. Understanding murmur physiology is also high yield in general. In this case, we
have a cyanotic heart condition in a newborn. Tetralogy of Fallot is the most common cyanotic
heart lesion on tests and in real life. ASDsfixed split S2are left-to-right (non-cyanotic lesions),
at least until they reverse down the line (Eisenmenger syndrome). Clinically significant PDAs are
alluded to by their continuous machinery murmur.
131.

E This is what a correlation is. A negative r-value means that the relationship between the

variables is inverse (not direct), so as one goes up, the other goes down.*
132.

A An annular pancreas occurs when the pancreas is wrapped around the second

(descending) portion of the duodenum. When symptomatic (in adults, typically when there is
superimposed pancreatitis), it can block flow of GI contents through the intestines.*
133.

B The left sided system is much higher pressure than the right side, hence the aortic valve

closing is usually louder than pulmonic valve. A P2 louder than A2 means that the pulmonary
artery pressure is significantly elevated.*

134.

E Calcium oxalate stones are the most common variety of kidney stones, but uric acid

stones make up 5-10% as well. None of the other choices are associated with renal calculi of any
variety.*
135.

E The patients 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.*
136.

H Furosemide is the prototypical loop diuretic, which works by blocking the triporter and

preventing the reabsorption of 1 K, 1 Na, and 2 Cl ions. So less K/Na/Cl ion transport
causes decreased osmolarity of the medullary interstitium (where these ions would normally
enter). Water follows solute, so with less ions reabsorbed, less water will be reabsorbed.
137.

B Surgical portosystemic shunts are most often performed by anastomosing the splenic vein

to the nearby left renal vein. The splenic and SMV join to form the main portal vein. are portal
system veins. More commonly, a TIPS procedure is performed to create an intrahepatic shunt
between the portal and hepatic veins.*
138.

C If an adult is taking on behaviors common to children, its called regression (dont feel

bad if its something you might do yourself).