Biochemistry › Fructose and Galactose Metabolism
Question 1
A 6-day-old newborn is brought to the emergency department because he has been increasingly sleepy and is feeding poorly. His parents say he initially latched well, but over the past two days he often falls asleep mid-feed and then vomits shortly afterward. He has had fewer wet diapers, and his stools have become looser, which the parents thought was “normal adjustment” to feeding. The mother mentions the baby was fussy the first night home and the family tried a different brand of cow’s milk–based formula once, but they went back to breastfeeding because it seemed gentler. Today, the parents noticed his skin looks more yellow, and his belly seems “puffy.” He has no fever, but he had one episode of shaking chills that stopped after bundling him, and the family wonders if the house is too cold. On exam he is lethargic, mildly hypotonic, and has hepatomegaly. Labs show: glucose 54 mg/dL, total bilirubin 8.6 mg/dL, AST 210 U/L, ALT 180 U/L, and INR 1.9. In this disorder, accumulation of which molecule will most likely be seen?
- A. Mannose-6-phosphate
- B. Sorbitol
- C. Galactitol
- D. Fructose-1-phosphate
- E. Lactate
- F. Galactose-1-phosphate
- G. UDP-glucose
Show answer and explanation
Correct answer: F. Galactose-1-phosphate
Core concept
This vignette tests classic galactosemia due to galactose-1-phosphate uridyltransferase (GALT) deficiency, which causes accumulation of galactose-1-phosphate with neonatal jaundice, hepatomegaly, hypoglycemia, poor feeding, vomiting, lethargy, and risk of E. coli sepsis.
Explanation
In GALT deficiency, ingested lactose (galactose) cannot be converted to UDP-glucose via the Leloir pathway, so galactose is phosphorylated to galactose-1-phosphate but cannot be exchanged for UDP‑glucose, causing intracellular buildup of galactose-1-phosphate that is hepatotoxic and interferes with glycogen metabolism and gluconeogenesis; excess galactose is also reduced to galactitol by aldose reductase causing cataracts, and patients present in the first days after exposure to breast milk or cow’s milk formula with jaundice, hepatomegaly, coagulopathy, hypoglycemia, vomiting, and lethargy.
Cardiology › Shock States (Cardiogenic, Hypovolemic, Distributive, Obstructive)
Question 2
A 27-year-old man is brought to the ED after a fall from a ladder while cleaning gutters. Witnesses say he briefly stood up but then collapsed again when he tried to walk. He has an abrasion on his forehead, a tender left wrist, and complains of tingling in both hands. He denies chest pain, cough, or recent illness. Temperature is 36.5°C (97.7°F), blood pressure is 78/44 mm Hg, pulse is 52/min, respirations are 18/min, and SpO₂ is 99% on room air. His skin is warm and dry; capillary refill is brisk. Neck veins are flat at 45°. Heart sounds are regular without extra sounds; lungs are clear to auscultation. Focused assessment sonography of the abdomen shows no free fluid. Bedside echocardiography reveals normal left ventricular size and contractility. Neurologic exam shows decreased pinprick below C6 with reduced lower-extremity tone. After 2 liters of isotonic fluid, blood pressure increases only slightly, and the heart rate remains low. Which hemodynamic profile best characterizes his current state?
- A. ↑ Cardiac Output → ↓ SVR → ↑ PCWP → ↑ Mixed Venous O₂ Saturation
- B. ↓ Cardiac Output → ↑ SVR → ↓/Normal PCWP → ↓ Mixed Venous O₂ Saturation
- C. ↑ Cardiac Output → ↓ SVR → ↓ PCWP → ↑ Mixed Venous O₂ Saturation
- D. ↑ Cardiac Output → ↑ SVR → ↑ PCWP → ↓ Mixed Venous O₂ Saturation
- E. Normal Cardiac Output → Normal SVR → ↑ PCWP → Normal Mixed Venous O₂ Saturation
- F. ↓ Cardiac Output → ↓ SVR → ↓ PCWP → ↑ Mixed Venous O₂ Saturation
- G. ↓ Cardiac Output → ↑ SVR → ↑ PCWP → ↓ Mixed Venous O₂ Saturation
Show answer and explanation
Correct answer: F. ↓ Cardiac Output → ↓ SVR → ↓ PCWP → ↑ Mixed Venous O₂ Saturation
Core concept
This vignette tests recognition of neurogenic (distributive) shock from high cervical spinal cord injury, characterized by loss of sympathetic tone producing hypotension with bradycardia, warm dry skin, and low systemic vascular resistance.
Explanation
A high cervical cord injury disrupts sympathetic outflow causing profound vasodilation (↓ SVR) and venous pooling (↓ preload → ↓ PCWP) while unopposed parasympathetic tone produces bradycardia and reduced cardiac output; bedside echo showing normal contractility and flat neck veins after fluids supports a vasodilatory/preload problem rather than cardiogenic or hypovolemic shock, and decreased tissue O2 extraction in distributive states paradoxically raises mixed venous O2 saturation.
Answer-choice discussion
_____ 1. ↓ Cardiac Output → ↑ SVR → ↓/Normal PCWP → ↓ Mixed Venous O₂ Saturation This represents cardiogenic shock with compensatory vasoconstriction and increased extraction (low mixed venous O2), but the patient has warm extremities, bradycardia, and normal LV contractility, which argue against cardi
Microbiology › Gram-Negative Bacteria
Question 3
A 52-year-old man is admitted after a house fire with partial-thickness burns on his arms and chest. He has a history of type 2 diabetes and takes metformin, and he mentions chronic knee pain treated with intermittent NSAIDs. On hospital day 6, he develops fever and increasing pain around one burn site, along with new confusion. The wound has a sweet odor per nursing staff, and drainage is purulent with a green tint on the dressings. Temperature is 39.2°C (102.6°F), heart rate 124/min, and blood pressure 86/48 mm Hg after fluids. Lactate is 4.8 mmol/L, creatinine is 2.1 mg/dL, and platelets are 92,000/mm³. Cultures grow an oxidase-positive gram-negative rod. What is the key chemical reaction is associated with the suspected pathogen?
- A. Ubiquitination
- B. Phosphorylation
- C. Methylation
- D. ADP ribosylation
- E. Deamidation
- F. Protease cleavage
- G. GTP hydrolysis
Show answer and explanation
Correct answer: D. ADP ribosylation
Core concept
This vignette tests recognition of Pseudomonas aeruginosa burn wound infection and its exotoxin-mediated mechanism; Pseudomonas produces exotoxin A that inactivates elongation factor-2 via ADP-ribosylation, halting protein synthesis.
Explanation
The patient’s burn wound, green purulent drainage, sweet/grape-like odor, oxidase-positive gram-negative rod, and sepsis physiology (fever, hypotension, elevated lactate, acute kidney injury, thrombocytopenia) point to Pseudomonas aeruginosa; its major virulence factor, exotoxin A, catalyzes ADP-ribosylation of elongation factor-2 (EF-2), preventing translocation during protein synthesis and causing host cell death and tissue necrosis that worsens wound infection and systemic toxicity. This question contrasts enzymatic toxin mechanisms common on Step 1: ADP-ribosylation (exotoxin A, diphtheria toxin, cholera toxin) versus other posttranslational or enzymatic actions.
Answer-choice discussion
_____ Ubiquitination; Ubiquitination tags eukaryotic proteins for proteasomal degradation and is not the mechanism of Pseudomonas exotoxin A or typical acute bacterial exotoxins in burn sepsis.
_____ Phosphorylation; Phosphorylation is a common signaling modification by kinases but is not the primary
Neurology and Special Senses › Brain, Spinal Cord, and Cranial Nerve Lesions
Question 4
A 72-year-old woman is brought to the hospital because of sudden weakness on the right side of her body that began 45 minutes ago while she was gardening. She reports that she suddenly dropped her tools and could not support her weight on the right leg, causing her to sit down on the ground. Her medical history includes long-standing hypertension, atrial fibrillation, hyperlipidemia, osteoarthritis, and a remote history of treated breast cancer. She admits that she skipped her last dose of anticoagulant medication yesterday after noticing a small nosebleed. On examination pinprick and temperature is preserved in all extremities. However, she has marked difficulty sensing vibration at the right great toe and accurately identifying the position of the right foot with her eyes closed, while these modalities are intact on the left side. When asked to protrude her tongue, it deviates toward the left, and subtle atrophy is noted along the left lateral aspect. Light touch over the face and limbs is intact, and visual fields appear full. A lesion in which of the following structures most likely explains this patient’s symptoms?
- A. Medial lemniscus
- B. Corticospinal tract
- C. Dorsal column in lumbar spinal cord
- D. Spinal trigeminal nucleus
- E. Lateral lemniscus
- F. Spinothalamic tract
- G. Nucleus ambiguus
Show answer and explanation
Correct answer: A. Medial lemniscus
Core concept
Sudden contralateral loss of vibration and proprioception with an ipsilateral hypoglossal palsy localizes to the medial brainstem where the medial lemniscus and hypoglossal nucleus/nerve run together (classic medial medullary territory).
Explanation
The patient has acute contralateral (right-sided) impairment of vibration and position sense with preserved pain and temperature, plus left-sided tongue deviation and atrophy, indicating a left medial medullary lesion that injures the medial lemniscus (carrying dorsal column–medial lemniscal proprioceptive input after decussation) and the ipsilateral hypoglossal nucleus/nerve; the constellation fits medial medullary (Dejerine) syndrome where the medial lemniscus is responsible for the selective loss of fine touch and proprioception while spinothalamic and trigeminal pain pathways are spared. This explains why vibration/proprioception are lost contral
Pulmonology › Obstructive Lung Disease
Question 5
A 67-year-old man with 55 pack years of smoking reports progressive exertional breathlessness and unintentional weight loss over 6 months. He walks his dog daily but now needs frequent rests on slight inclines. He denies chest pain and has no orthopnea. Past history includes mild hypertension and treated peptic ulcer disease; he drinks two coffees daily and rarely drinks alcohol. Pulse oximetry is 93 percent on room air; end tidal CO₂ is slightly elevated. Hemoglobin is 11.9 g per dL, bicarbonate is 30 mEq per L, and BNP is normal. Chest radiograph shows flattened diaphragms and increased retrosternal airspace; there are no focal opacities. Spirometry reveals low FEV₁ to FVC ratio. At the end of a passive exhalation, his respiratory system rests at a different equilibrium than expected for his age. Which change is most likely expected from this patient?
- A. Decreased residual volume
- B. Increased airway smooth muscle tone at rest
- C. Increased closing capacity
- D. Increased lung elastic recoil
- E. Decreased chest wall outward recoil
- F. Decreased total lung capacity
- G. Increased functional residual capacity
Show answer and explanation
Correct answer: G. Increased functional residual capacity
Core concept
Smoking-induced emphysema causes loss of alveolar walls and lung elastic recoil leading to airflow obstruction and air trapping with hyperinflation; functional residual capacity (FRC) rises as the respiratory system equilibrium shifts outward.
Explanation
This patient’s progressive exertional dyspnea, heavy smoking history, flattened diaphragms, increased retrosternal airspace, low FEV1/FVC, mild chronic hypercapnia with metabolic compensation (elevated bicarbonate), and normal BNP point to COPD/emphysema with increased lung compliance and reduced elastic recoil; loss of recoil permits small airways to collapse during exhalation, producing air trapping and a higher end-expiratory lung volume so the respiratory system rests at an increased FRC.
Answer-choice discussion
_____ Decreased residual volume Residual volume is increased in emphysema because air trapping prevents full expiration; a decreased RV would imply less trapping, which contradicts the hyperinflation seen on imaging. _____**Increased airway smooth muscle tone
Renal › Renal Pharmacology
Question 6
A 29-year-old man begins a medication for prevention of recurrent episodes of severe unilateral periorbital pain associated with tearing and nasal congestion. Two days later, arterial blood gas shows pH 7.31, PCO2 30 mm Hg, and HCO3- 15 mEq/L. Serum potassium is 3.9 mEq/L. Urinalysis shows alkaline urine. Which nephron transport process is most directly inhibited by this drug?
- A. Luminal carbonic anhydrase
- B. NKCC2 cotransporter
- C. NCC cotransporter
- D. ENaC channel
- E. Na+/K+ ATPase
Show answer and explanation
Correct answer: A. Luminal carbonic anhydrase
Core concept
Carbonic anhydrase inhibition in the proximal tubule causes loss of HCO3− leading to normal anion gap metabolic acidosis with respiratory compensation and alkaline urine from bicarbonaturia; acetazolamide is used for prophylaxis of cluster headaches.
Explanation
Acetazolamide inhibits luminal carbonic anhydrase in proximal tubule cells, preventing conversion of filtered H2CO3 to CO2 and H2O for reabsorption, thereby increasing urinary HCO3− excretion which raises urine pH and produces a metabolic acidosis (low HCO3− with compensatory low PCO2); the acute timeframe (days) and presence of alkaline urine are classic for proximal carbonic anhydrase blockade rather than loop or thiazide diuretics, and the normal serum K+ helps differentiate from diuretics that cause significant hypokalemia.
Answer-choice discussion
Luminal carbonic anhydrase This is correct—blocking luminal CA in the proximal
