Free USMLE Step 1 Respiratory and Renal practice questions

Most nonprescription sleep aids contain a first-generation H1 antihistamine, diphenhydramine or doxylamine. These drugs are lipophilic and cross the blood-brain barrier, where H1 blockade causes sedation, the effect exploited as a sleep aid. They also lack receptor selectivity and are potent muscarinic antagonists. This man shows the anticholinergic picture: delirium, mydriasis, dry mouth and skin, mild hyperthermia, tachycardia, decreased bowel sounds and urinary retention. Blocking M3 receptors on the detrusor removes the parasympathetic drive for bladder contraction, and in a man with prostatic enlargement this readily precipitates acute retention. Central muscarinic blockade causes delirium, to which older adults are especially vulnerable. For these reasons first-generation antihistamines are on the Beers list of drugs to avoid in older adults. They also block α1 receptors, causing orthostatic hypotension. Second-generation agents are P-glycoprotein substrates with little CNS entry and minimal antimuscarinic activity.

A. α1 stimulation at the bladder neck causes retention with decongestants such as pseudoephedrine, but it would not explain delirium, dry skin and mydriasis; diphenhydramine blocks rather than stimulates α1 receptors. B. Peripheral H1 inverse agonism relieves itch, sneezing and rhinorrhea and does not cause urinary retention. D. GABA-A modulation (benzodiazepines, zolpidem) causes sedation and confusion but not mydriasis, dry skin or retention. E. D2 blockade is the action of antipsychotics and antiemetics such as prochlorperazine and causes extrapyramidal effects rather than this toxidrome.

A mild, prolonged "walking pneumonia" in a college student with dormitory contacts, dry cough, interstitial infiltrates that look worse than the patient, failure of amoxicillin, no organisms on Gram stain, and cold agglutinins (IgM against the I antigen on red cells) indicate Mycoplasma pneumoniae.

The Gram stain depends on peptidoglycan. Crystal violet and iodine form a complex that a thick peptidoglycan wall traps through the alcohol wash (gram-positive), while a thin wall loses it and takes up safranin (gram-negative). Mycoplasma has no cell wall at all; its plasma membrane is stabilized by sterols taken from the host or medium, which is why it is grown on Eaton agar supplemented with cholesterol. With no wall it neither retains nor reliably shows on the stain, and because β-lactams act by blocking penicillin-binding proteins that build peptidoglycan, they have no target. Macrolides, doxycycline, or respiratory fluoroquinolones are used.

A. A mycolic acid wall explains why mycobacteria stain poorly and are acid-fast; it does not explain cold agglutinins, and TB is not a dormitory outbreak of mild pneumonia.

C. Being too thin to resolve is the reason Treponema and Leptospira are missed on Gram stain; they are spirochetes seen by dark-field microscopy.

D. β-lactamase would explain amoxicillin failure in organisms such as Moraxella or nontypeable H. influenzae, but those are visible as gram-negative organisms on stain.

E. A capsule does not prevent Gram staining; encapsulated S. pneumoniae appears as gram-positive lancet-shaped diplococci and responds to amoxicillin.

The organism is Pseudomonas aeruginosa: an oxidase-positive, non-lactose-fermenting gram-negative rod with a grapelike odor. In cystic fibrosis, Pseudomonas is usually acquired in later childhood or adolescence, at first intermittently. Under the selective pressure of the dehydrated, hypoxic CF airway and repeated antibiotic exposure, it switches to a mucoid phenotype that overproduces alginate, an exopolysaccharide. Alginate forms the matrix of a biofilm in the thick mucus. The biofilm shields bacteria from neutrophil phagocytosis, complement and antibodies, and it slows antibiotic penetration and bacterial growth, so the infection becomes chronic and essentially impossible to eradicate. Chronic mucoid Pseudomonas is the most common airway pathogen in adults with CF and accelerates the decline in FEV1, as in this patient.

A. Exotoxin A ADP-ribosylates elongation factor 2 and kills host cells, contributing to tissue damage, but it does not protect bacteria from antibiotics or phagocytes.

C. Pyocyanin is a blue-green redox-active pigment that generates reactive oxygen species and damages ciliated epithelium; it explains green sputum, not persistence through antibiotic therapy.

D. Protein A is a Staphylococcus aureus surface protein that binds the Fc portion of IgG. S. aureus colonizes CF airways mainly in childhood and is gram-positive.

E. Elastase degrades elastin, immunoglobulins and complement and contributes to airway destruction, but the slimy colonies and chronic antibiotic-resistant carriage point to alginate biofilm.

Osteomalacia with isolated hypophosphatemia, renal phosphate wasting, normal calcium, normal PTH and an inappropriately low calcitriol that resolves after removal of a small mesenchymal tumor is tumor-induced (oncogenic) osteomalacia, caused by ectopic FGF23. FGF23, acting with its co-receptor Klotho in the proximal tubule, has two effects. It down-regulates the NaPi cotransporter, causing phosphaturia, and it inhibits renal 1-alpha-hydroxylase, lowering calcitriol. Normally hypophosphatemia would strongly stimulate 1-alpha-hydroxylase, so a low calcitriol in the face of a low phosphate is the fingerprint of FGF23 excess. Low calcitriol also reduces gut phosphate absorption, deepening the deficit, and the lack of phosphate impairs mineralization of osteoid. The absence of glucosuria and aminoaciduria excludes Fanconi syndrome. The same hormone excess underlies X-linked hypophosphatemic rickets (PHEX mutation).

A. PTH also causes phosphaturia, but it stimulates 1-alpha-hydroxylase (raising calcitriol) and raises serum calcium; his PTH is normal. B. PTHrP mimics PTH and would produce hypercalcemia, the classic paraneoplastic effect of squamous cell carcinomas and renal cell carcinoma. C. Excess calcitriol, as from granulomas, raises gut absorption of both calcium and phosphate, causing hypercalcemia and normal or high phosphate. D. Calcitonin inhibits osteoclasts and has minimal physiologic effect on serum calcium or phosphate in humans; it is the marker of medullary thyroid carcinoma.

Prolonged hypotension followed by oliguria, a FENa above 2%, isosthenuric urine (osmolality below 350) and muddy brown granular casts define ischemic acute tubular necrosis. A BUN:creatinine ratio of about 14 fits as well, because damaged tubules no longer reclaim urea with sodium and water.

Ischemia does not injure the nephron evenly. The most vulnerable segments are the proximal straight tubule (S3) and the medullary thick ascending limb. Both sit in the outer medulla, where oxygen tension is low even in health because the vasa recta carry little blood, and both have a very high metabolic demand from active Na+ transport. When perfusion falls, these cells run out of ATP first, lose polarity and slough. The dead cells form casts that obstruct the lumen, filtrate leaks back across the bare basement membrane, and extra NaCl reaching the macula densa constricts the afferent arteriole through tubuloglomerular feedback. Together these cut GFR. Because the basement membrane is usually intact, the epithelium can regenerate, and recovery passes through a polyuric phase.

A. Podocyte injury causes proteinuria and nephrotic syndrome, not granular casts with a high FENa.

B. The convoluted proximal tubule in the cortex is better oxygenated; nephrotoxins such as aminoglycosides injure the proximal tubule broadly, but ischemia targets the straight (S3) part in the outer medulla.

D. The thin limbs have low transport work and little oxygen demand, so they resist ischemia.

E. Collecting duct principal cells are not the primary site of ischemic ATN; their dysfunction would mainly impair K+ secretion and water reabsorption.

In states of reduced effective circulating volume such as heart failure, volume depletion, cirrhosis, or chronic kidney disease, high levels of angiotensin II and sympathetic tone constrict the renal vasculature. Glomerular filtration is then preserved by locally produced prostaglandins (PGE2 and PGI2), which dilate the afferent arteriole and maintain glomerular plasma flow. Nonselective NSAIDs such as indomethacin block COX-1 and COX-2 (COX-2 is constitutive in the kidney), removing this vasodilation. Unopposed afferent constriction lowers glomerular hydrostatic pressure and GFR, producing a hemodynamic, prerenal acute kidney injury with oliguria, a bland urinalysis, and a low fractional excretion of sodium. Her concurrent ACE inhibitor (which prevents compensatory efferent constriction) and loop diuretic complete the classic high-risk combination. The injury usually reverses when the NSAID is stopped.

A. Angiotensin II constriction of the efferent arteriole supports GFR; her lisinopril reduces this effect, and an increase in efferent tone would raise, not lower, filtration. B. A cell-mediated hypersensitivity reaction is acute interstitial nephritis, which NSAIDs can also cause, but it typically presents with sterile pyuria, white cell casts, and sometimes eosinophiluria, and often nephrotic-range proteinuria with NSAIDs. C. Uric acid crystal precipitation in collecting ducts causes acute urate nephropathy in tumor lysis syndrome, with very high serum urate. D. Direct tubular necrosis (aminoglycosides, contrast, prolonged ischemia) produces muddy brown granular casts and a fractional excretion of sodium above 2%.

Growth in parallel serpentine ribbons is the colony behavior that gave cord factor, or trehalose dimycolate, its name, and it is found in virulent strains. Cord factor impairs maturation of the macrophage and triggers release of TNF-α, the cytokine that recruits monocytes and holds the granuloma together. Injecting it alone is enough to produce granuloma-like macrophage aggregates, which is exactly what the mice developed. This is why TNF-α blocking drugs dissolve existing granulomas and allow latent tuberculosis to reactivate, often in extrapulmonary or disseminated form.

A. Lipoarabinomannan modulates signaling and helps the bacillus survive in macrophages, but it does not cause serpentine cord growth and is present in avirulent mycobacteria as well. C. Arabinogalactan is the structural polysaccharide that anchors mycolic acids to peptidoglycan; it is the target of ethambutol and is not a strain-specific virulence glycolipid. D. Lipoteichoic acid is a component of gram-positive bacterial walls and is absent from mycobacteria. E. Peptidoglycan is present in essentially all bacteria and is not responsible for cording or for strain-specific TNF-α release.

A separate family of mycobacterial glycolipids, the sulfatides, blocks fusion of the phagosome with the lysosome, allowing bacilli to survive inside resting macrophages.

Diabetic ketoacidosis with facial pain, bloody nasal discharge, proptosis, ophthalmoplegia, a black necrotic eschar on the palate and turbinate, and sinus disease eroding bone is rhinocerebral mucormycosis, caused by molds of the order Mucorales such as Rhizopus and Mucor.

Ketoacidosis favors these fungi in several ways: acidosis releases iron from transferrin, and Rhizopus thrives on free iron; hyperglycemia and acidosis impair neutrophil chemotaxis and killing; and the organisms grow well in glucose-rich, acidic tissue. Spores inhaled into the nose and sinuses germinate into hyphae that invade blood vessel walls, causing thrombosis and ischemic infarction, which produces the black eschar. The infection spreads to the orbit and through the cribriform plate or cavernous sinus to the brain. Tissue shows broad, ribbon-like, irregular hyphae with few or no septa that branch at wide (near 90°) angles. Treatment is urgent surgical debridement plus amphotericin B and correction of the acidosis.

A. Narrow septate hyphae with acute (about 45°) branching are Aspergillus, which causes invasive disease mainly in profound neutropenia and is treated with voriconazole.

B. Budding yeasts with pseudohyphae are Candida, which causes thrush, esophagitis, and candidemia, not a necrotic palatal eschar in DKA.

D. Spherules with endospores are Coccidioides, an endemic fungus of the southwestern US that causes pneumonia and valley fever.

E. Broad-based budding yeast is Blastomyces, which causes pneumonia with verrucous skin and bone lesions.

A young woman with bilateral, multifocal clear-cell renal cell carcinoma, a prior cerebellar hemangioblastoma, a family history of pheochromocytoma and a 3p germline mutation has von Hippel-Lindau disease (autosomal dominant, VHL at 3p25). The VHL protein is the substrate-recognition part of an E3 ubiquitin ligase. In normal oxygen conditions, HIF-1-alpha is hydroxylated on proline residues, and VHL binds the hydroxylated HIF and tags it with ubiquitin for proteasomal degradation. When both VHL alleles are lost (germline plus a somatic second hit), HIF is stabilized even in normoxia and moves to the nucleus to drive VEGF, PDGF and erythropoietin transcription. VEGF explains the richly vascular tumors (clear-cell RCC, hemangioblastomas), and erythropoietin explains her polycythemia. Sporadic clear-cell RCC usually shares the same pathway through 3p deletion, and VEGF-targeting tyrosine kinase inhibitors exploit it.

A. Neurofibromin (NF1) is a Ras GTPase-activating protein; its loss causes neurofibromas, cafe-au-lait spots and pheochromocytoma, but not renal clear-cell tumors and hemangioblastomas. B. Tuberin (TSC2) inactivates Rheb to restrain mTOR; tuberous sclerosis causes renal angiomyolipomas. D. RB binds E2F to hold cells in G1; its loss causes retinoblastoma and osteosarcoma. E. Mismatch repair proteins (MLH1, MSH2) are lost in Lynch syndrome, which favors urothelial carcinoma of the renal pelvis and ureter rather than clear-cell RCC.

Thyroidectomy can injure both recurrent laryngeal nerves, which supply all intrinsic laryngeal muscles except the cricothyroid. Paralyzed cords cannot abduct, and because they are flaccid, they behave as a variable extrathoracic obstruction.

Whether a variable lesion narrows depends on the pressure outside versus inside the airway. Outside the chest, the surrounding pressure is atmospheric. During forced inspiration, intraluminal pressure falls below atmospheric, so the floppy cords are sucked inward and flow is capped, producing a flat inspiratory plateau. During forced expiration, intraluminal pressure is above atmospheric, the cords are pushed apart, and the expiratory limb is normal. This matches her inspiratory stridor.

A. A scooped expiratory limb at high lung volumes reflects dynamic compression of small airways and air trapping in asthma or COPD.

B. A small, tall loop at low volumes is the restrictive pattern of interstitial lung disease or chest wall disease.

C. Flattening of both limbs indicates a fixed obstruction that ignores transmural pressure, such as post-intubation tracheal stenosis or a goiter encasing the trachea.

E. Expiratory flattening alone indicates a variable intrathoracic lesion (intrathoracic tracheomalacia, lower tracheal tumor), compressed by positive pleural pressure during forced expiration.