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4 of the Hardest Practice Questions for USMLE Step 1

Monday, February 11, 2019
By The TrueLearn Team

Post Updated for 2019:

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Spring is here and that generally means one thing for MS2s – the USMLE Step 1 exam is just a few weeks away.

You’re undoubtedly studying hard and looking for the best books, Q-banks and resources to help you prep. TrueLearn’s SmartBank (next-generation Q-bank) features 2,000+ practice questions for the USMLE Step 1 exam, and we’ve hand-picked some of the toughest questions to share with you during your prep.

Give them a shot and see how you do!

USMLE Step 1 Practice Questions from TrueLearn

Question #1

Q: A veterinary student is studying the genetics behind inheritance of coat colors in cats. He has cats that are black and cats that are orange. He notes that when two cats that are black are mated, all the offspring are black. Likewise, when two orange cats are mated, the resulting offspring are orange. When a black male cat is mated with an orange female cat, all the male cats are orange but the female cats have patches of orange and black. When an orange male cat is mated with a black female cat, all the male cats are black but female cats have patches of orange and black. He believes that the gene for fur color is carried on the X chromosome. In female cats that inherit X chromosomes with different alleles, the resulting coat has patches of each color due to random inactivation of a single X chromosome. This is an example of which of the following?

A) Codominance

B) Imprinting

C) Incomplete Penetrance

D) Mosaicism

E) Pleiotropy

Question #2

Q: A 14-month-old male child with no past medical history is brought to the emergency department with vomiting, colicky abdominal pain, and several bowel movements containing both blood and mucus. He has a heart rate of 114 beats/minute, a respiratory rate of 22 breaths/minute, a blood pressure of 104/79 mmHg, and a temperature of 36.4oC. Right upper and lower quadrant tenderness can be elicited on palpation without rebound tenderness or tympany, and a sausage-shaped mass can be palpated in the right lower quadrant. A stool sample appears as “currant jelly” and is positive for blood. Laboratory assessment is as follows: Hemoglobin 14.5 mg/dL Hematocrit 47% WBC 7,400 cells/mm3 Platelets 180,000 cells/mm3 Ultrasonography confirms the diagnosis. What is the best treatment for this clinical presentation?

A) Barium or air enema

B) Bowel rest

C) Emergent appendectomy

D) Exploratory laparotomy

E) Oral metronidazole

Question #3

Q: A 34 year-old woman presents to the emergency department with a 6-month history of recurrent epistaxis and easy bruising. She has experienced approximately two to three epistaxis episodes per month during this period, and the bleeds eventually stops following packing of the anterior nares. She has no past medical or surgical history and takes no medications. She has never been pregnant but notes that her menstrual periods have been “more heavy than usual” during the same 6 months. She denies headaches or changes in vision. On examination, she is afebrile, has a pulse of 78 beats/minute and a blood pressure of 119/82. On dermatologic examination, she has diffuse areas of petechiae under her tongue, on the extensor surfaces of her forearms, and on her posterior thighs bilaterally, none of which are elevated or palpable. Abdominal exam is negative for splenomegaly. Laboratory examination shows: BUN 13 mg/dL Creatinine 0.8 mg/dL WBC 8,000 cells/mm3 Platelets 24,000 platelets/mm3 Hemoglobin 14.1 mg/dL Hematocrit 42% PT 14 seconds (normal 11-15 seconds) aPTT 27 seconds (normal 25-40 seconds) Bleeding time 11 minutes (normal 2-7 minutes) What is the most likely diagnosis for this patient’s condition?

A) Hemophilia A

B) Heparin-induced thrombocytopenia

C) Immune thrombocytopenic purpura

D) Thrombotic thrombocytopenic purpura

E) Von Willebrand’s disease

Question #4

A 30-year-old female presents with abdominal pain, nausea, vomiting that began two days ago. She has a past medical history significant for chronic hepatitis B infection, which has been stable, and a long-standing history of intravenous drug abuse. Laboratory results are remarkable for severely elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as elevated total bilirubin. A hepatitis panel confirms the diagnosis of hepatitis D infection. Which of the following best describes the mechanism by which hepatitis B facilitates infection by hepatitis D virus?

A) Activation of HDV RNA replication

B) Production of proteins that coat HDV viral particles

C) Regulation of HDV RNA transcription

D) Stabilization of the HDV genome

E) Upregulation of HDV receptors on hepatocytes

Answers & Analysis

Question #1

Correct Answer: D

This is an example of mosaicism. Mosaicism occurs when there are cell lines containing two or more different genetic makeups leading to different phenotypes. In this case, random inactivation of an X chromosome leads to different genotypes expressed in patches. Since the gene that determines coat color is present on the X chromosome, this leads to patches of fur that are different colors.
Answer A: In codominance, the two different alleles are expressed at the same time and neither allele is dominant. The ABO blood group system is an example.
Answer B: Imprinting refers to a difference in phenotype depending on whether the mutation is present on the paternal or maternal chromosome. The different phenotypes seen from inheritance from male or female cats is a result of X chromosome inheritance rather than imprinting.
Answer C: Incomplete penetrance occurs when some of those that inherit a particular genotype do not express that phenotype.
Answer E: Pleiotropy refers to the presence of more than one manifestation due to a mutation in a single gene. For example, a single mutation in the cystic fibrosis gene can cause respiratory disease, pancreatic disease, and infertility.

Bottom Line: Mosaicism refers to the presence of more than one genetic makeup of cells occurring in the same individual. X chromosome inactivation is a common cause. For more information, see Harrison’s Internal Medicine, 18th Ed. “Chapter 61: Principles of Human Genetics”

Question #2

Correct Answer: A

This child is most likely suffering from intussusception, which refers to a process in which a segment of the intestinal tract invaginates into an adjoining lumen. The majority of cases in infant and toddler children are idiopathic, and involve a “telescoping” of one section of bowel into another due to an imbalance of peristaltic forces between adjacent segments of bowel. The “telescoping” action can also pull attached mesentery inwards, leading to lymphatic obstruction, bowel wall edema, venous impedance, and finally blockage of arterial blood flow to the trapped segment. Cessation of delivery of oxygenated blood leads to ischemia, infarction, and necrosis. A frequent predisposing factor to development of intussusception in older children and adults is the presence of a lead point, which promotes development of an imbalance of peristaltic forces. In this older population, intussusception is more commonly observed in association with other medical factors, including cystic fibrosis (CF), Henoch-Schonlein Purpura (HSP), intestinal or lymphatic tumors, submucosal hematoma secondary to coagulopathy, sutures or staples, foreign body, or rarely as a post-operative complication of laparatomy. Since the presence of lead point is more likely in older children and adults, surgical reduction is favored in children older than 3 who present with symptoms and radiologic evidence suggestive of intussusception. This method of management has a greater chance of addressing the underlying issue and preventing future recurrence while restoring blood flow to threatened bowel. Because of this patient’s age and lack of comorbid conditions, idiopathic intussusception is a more likely diagnosis. Therapeutic enema (either barium or air) is indicated in order to reduce the intussusception non-operatively. These procedures are widely practiced and vary in effectiveness (40-90%) depending on operator experience. The absolute contraindications to barium or air enema are presence of peritonitis suggested by clinical findings, or suggestiong of perforation on radiographic films (i.e. free air under the diaphragm).

Answer B: Bowel rest is not indicated in this patient because it does not address the underlying intussusception pathology and can precipitate bowel gangrene and perforation due to failure to improve bowel ischemia.

Answer C: Emergent appendectomy is not indicated in this clinical scenario, as this patient does not have signs or symptoms suggestive of appendicitis, including fever, leukocytosis, or tenderness at McBurney’s point.

Answer D: Exploratory laparotomy is not indicated in this clinical scenario because the etiology is not likely to involve a lead point, making non-operative reduction with barium or air enema more likely to succeed and recurrence less likely.

Answer E: Oral metronidazole is not indicated in this patient as a bacterial overgrowth is not likely based on lack of suggestive clinical findings, including fever and leukocytosis.

Bottom Line: Intussusception is a common cause of abdominal pain in infants and toddlers, and is classically characterized by vomiting, abdominal pain, and bloody, “currant-jelly” stools. In non-complicated intussusception in infants and toddlers, non-operative reduction with air or barium enema is effective and safe. For more information, please see

Question #3

Correct Answer: C

The most likely diagnosis for this patient’s condition is chronic Immune Thrombocytopenic Purpura (ITP). It is predominantly an acquired condition that is characterized by the formation of IgG antibodies against the patient’s own platelet glycoprotein antigens, including glycoproteins IIb-IIIa and Ib-IX. Antibody-mediated opsonization of platelets leads to phagocyte recognition via binding to macrophage FcγRIIA or FcγRIIA receptors, and and subsequent platelet sequestration in the spleen, leading to an absolute decrease in platelet counts. In addition, megakaryocyte maturation can also be affected by antibody binding, leading to decreased ability of the bone marrow to produce new platelets. The combination of these two factors causes easy bleeding as well as formation of petechiae, which are punctate areas of bleeding caused by failure of platelet plug formation. These are often seen in dependent areas of the body due to increased intracapillary pressure at these locations. Laboratory examination shows both a normal prothrombin time (PT) and a normal activated partial thromboplastin time (aPTT), with a prolonged bleeding time, indicating an relatively-intact coagulation cascade and either a qualitative or quantitative (in this case, quantitative) platelet defect. A different form of ITP is the acute form, which is usually seen in children in a few weeks after a viral illness.

Answer A: Hemophilia A is an X-linked recessive condition, so it would be unlikely for it to manifest in a female. In addition, the patient has normal aPTT, which would be prolonged in hemophilia A.

Answer B: Heparin-Induced Thrombocytopenia (HIT) is unlikely in this patient as she has had no recent reported contact with heparin. It occurs in approximately 5% of patients receiving heparin and is due to antibody formation against complexes of heparin and platelet factor 4 (PF4). Severe forms of this disorder lead to thrombosis from platelet activation.

Answer D: Thrombotic thrombocytopenic purpura (TTP) is diagnosed by a classic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure, although most patients may lack one or more of the five criteria. It is caused by excessive activation of platelets, leading to microthrombus formation in capillary beds. It is unlikely in this patient due to the insidious clinical course and lack of organ dysfunction.

Answer E: Von Willebrand’s Disease (vWD) is the most common inherited bleeding disorder affecting 1% of adults due to a qualitative or quantitative defect in von Willebrand’s factor (vWF). It often causes less severe episodes of hemorrhage than hemophilia A, including epistaxis, menorrhagia, and gingival bleeding. Patients with vWD usually have a qualitative defect in platelet function despite a normal platelet count. It may also cause a prolongation of aPTT due to the physiologic function of vWF to stabilize factor VIII.

Bottom Line: Chronic Immune thrombocytopenic purpura (ITP) in adults is generally a chronic condition associated with formation of non-palpable petechiae formation and mucous membrane bleeding. Laboratory examination generally shows a low platelet count, a normal PT and aPTT, and a prolonged bleeding time. For more information, see

Question #4

Correct Answer: B

Hepatitis D infection requires the presence of hepatitis B virus (HBV) because it cannot complete virion assembly and secretion independently; therefore, patients with symptomatic hepatitis D virus (HDV) infection are always co-infected with HBV, such as this patient. In individuals susceptible to HBV infection, co-infection with HDV is usually clinically very similar to acute hepatitis B infection. HBV assists with HDV infection by providing the lipoprotein envelope of HDV. This envelope consists of the same proteins that are found in HBV and is crucial in the assembly of virions and their ability to invade and infect other hepatocytes. How HDV induces liver disease remains largely unclear; however, it is known that the severity and duration of disease largely relates to the HDV genotype and host-associated immune responses.

Answer A: HDV RNA replication is activated by the small hepatitis D antigen (HDAg) through its direct binding to the HDV RNA. HBV is not involved in this process.

Answer C: Transcription of HDV RNA occurs inside the hepatocyte nucleus. The host RNA polymerase II is involved in the transcription of the HDV RNA, and HBV is not involved in this process.

Answer D: HBV is not involved in the stabilization of HDV genome.

Answer E: The receptor for HDV has not yet been elucidated. Currently HBV has not been shown to facilitate this step of the HDV life cycle.

Bottom Line: Hepatitis D infection always occurs concurrently with hepatitis B infection because the hepatitis B virus produces the lipoprotein envelope that is necessary for HDV assembly and dissemination. For more information, see: 1. Pathogenesis, epidemiology, natural history, and clinical manifestations of hepatitis D virus infection. 2. Diagnosis of hepatitis D virus infection. 3. Hepatitis D. Emedicine.

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