Free USMLE Step 1 Gastrointestinal practice questions

The pectinate (dentate) line marks the junction of hindgut endoderm above and proctodeum ectoderm below, and nearly every feature switches there. Below the line the canal is lined by stratified squamous epithelium, is innervated by the somatic inferior rectal nerve (so lesions hurt), is supplied by inferior rectal vessels draining to the internal iliac system and IVC, and drains lymph to the superficial inguinal nodes. This man has an HPV-16-driven squamous cell carcinoma below the line, a tumor associated with HIV infection and immunosuppression, so his first nodal spread is expected in the groin. Anal squamous cell carcinoma is treated first with chemoradiation using 5-FU and mitomycin, which preserves the sphincter.

A. Internal iliac nodes drain the canal above the pectinate line, where adenocarcinoma of columnar epithelium arises, and the middle rectal territory. C. Inferior mesenteric nodes drain the rectum and sigmoid along the superior rectal and sigmoid vessels, a hindgut pathway above the line. D. Para-aortic nodes are reached secondarily from iliac and mesenteric chains, not as a first station for a lesion below the line. E. Pararectal nodes along the superior rectal artery drain upper rectal mucosa and would be the first station for a rectal adenocarcinoma, not for a squamous lesion of the anoderm.

A reducible groin bulge extending into the scrotum in a premature infant boy, with a sac that enters the deep inguinal ring lateral to the inferior epigastric vessels and runs within the spermatic cord, is an indirect inguinal hernia, the most common hernia overall. As the testis descends, it is preceded by an outpouching of peritoneum, the processus vaginalis, which normally obliterates around birth except for the tunica vaginalis surrounding the testis. If it stays patent, abdominal contents can follow it through the deep ring (an opening in the transversalis fascia), along the inguinal canal and out the superficial ring into the scrotum, picking up all three spermatic fascial coverings. Prematurity and male sex raise the risk, and infant indirect hernias can incarcerate, so they are repaired promptly. A narrower patency that admits only peritoneal fluid causes a communicating hydrocele, which transilluminates.

Remember: MDs don't LIe, Medial = Direct, Lateral = Indirect.

B. Weak transversalis fascia in Hesselbach triangle causes a direct inguinal hernia, which emerges medial to the inferior epigastric vessels in older men. C. A femoral hernia passes below the inguinal ligament, medial to the femoral vein, and is more common in women. D. Incomplete testicular descent causes cryptorchidism, but both testes are in the scrotum. E. A patent urachus, the allantois remnant, leaks urine from the umbilicus.

Chronic acid and bile reflux injures the stratified squamous epithelium of the distal esophagus. Stem cells adapt by producing a cell type better able to withstand the injury: intestinal-type columnar epithelium with goblet cells. Replacement of one adult cell type by another is metaplasia, and in the esophagus it is called Barrett esophagus. Metaplasia is an adaptive change and can regress if the stimulus is removed, but persistent reflux can push it to dysplasia and then adenocarcinoma, so patients undergo surveillance endoscopy. In this biopsy the nuclei are small, basal and uniform without architectural disarray, which means there is no dysplasia yet.

A. Hyperplasia is an increase in the number of cells of the same type, such as endometrial hyperplasia from unopposed estrogen; it does not change the cell type. B. Low-grade dysplasia would show nuclear enlargement, hyperchromasia, stratification and loss of maturation toward the surface, which are absent here. D. Carcinoma in situ shows full-thickness atypia with an intact basement membrane; the cells here are cytologically bland. E. Hypertrophy is an increase in cell size without new cells, the only growth option for permanent tissues such as cardiac and skeletal muscle.

5-Fluorouracil is converted to 5-fluorodeoxyuridine monophosphate (5-FdUMP), which binds thymidylate synthase together with the folate cofactor 5,10-methylene-THF. In this covalent ternary complex the enzyme cannot methylate dUMP to dTMP, so DNA synthesis stops and cells die in S phase. The complex is stable only when methylene-THF is plentiful.

Leucovorin (5-formyl-THF) is an already reduced folate that enters the folate pool and expands the methylene-THF supply. This stabilizes and prolongs thymidylate synthase inhibition, so with 5-FU leucovorin potentiates cytotoxicity rather than rescuing cells. That is why it is given with or just before the 5-FU in FOLFOX and FOLFIRI, and why it also increases 5-FU toxicity such as mucositis and diarrhea.

A. Bypassing the DHFR block to rescue normal cells is leucovorin's role after high-dose methotrexate, not with 5-FU, which does not inhibit DHFR. B. Leucovorin does not inhibit dihydropyrimidine dehydrogenase; DPD deficiency is an inherited cause of severe 5-FU toxicity, and his DPYD genotype is normal. D. Thymidine phosphorylase performs the final step converting oral capecitabine to 5-FU in tissues; leucovorin does not induce it. E. Leucovorin has no chelating activity and does not prevent the cold-induced and cumulative sensory neuropathy of oxaliplatin.

Immunohistochemistry identifies the lineage and site of origin of a metastasis when the primary is unknown. Cytokeratin positivity (here CK20) establishes an epithelial tumor, and the CK7 and CK20 profile narrows the organ. A CK7-negative, CK20-positive adenocarcinoma is colorectal until proven otherwise, and nuclear CDX2, an intestinal transcription factor, strongly supports intestinal origin. The morphology fits as well: tall columnar cells forming glands with central "dirty" necrosis are typical of colorectal adenocarcinoma. The liver is the most common site of colorectal metastasis because the colon drains through the portal vein, so the liver is the first capillary bed tumor cells meet.

A. Lung adenocarcinoma is usually CK7-positive, CK20-negative and TTF-1-positive; his smoking history is a distractor, and TTF-1 is negative. B. Breast carcinoma is CK7-positive, CK20-negative and typically GATA3-positive. C. Pancreatic adenocarcinoma is usually CK7-positive, often with variable CK20, and is not typically strongly CDX2-positive with a CK7-negative profile. D. Urothelial carcinoma of the bladder is characteristically positive for both CK7 and CK20 and expresses GATA3, and it does not form tall columnar glands.

An older man with oropharyngeal dysphagia, regurgitation of undigested food eaten hours to days earlier, gurgling, halitosis, aspiration pneumonia, and a posterior pouch at the pharyngoesophageal junction has a Zenker diverticulum. It is a pulsion, or false, diverticulum, containing only mucosa and submucosa. The driving problem is cricopharyngeal (upper esophageal sphincter) dysfunction: the sphincter relaxes poorly, so each swallow raises hypopharyngeal pressure. The mucosa herniates posteriorly through Killian triangle, a weak area between the oblique thyropharyngeal fibers and the transverse cricopharyngeal fibers of the inferior pharyngeal constrictor. The pouch traps food, which ferments (halitosis) and is later regurgitated or aspirated. It usually extends to the left. A barium swallow is the diagnostic test, because blind endoscopy or nasogastric tube placement can perforate the pouch; treatment is cricopharyngeal myotomy with diverticulectomy or endoscopic septotomy.

A. A mid esophageal outpouching pulled by scarred nodes (after tuberculosis or histoplasmosis) is a traction diverticulum, a true diverticulum that is usually asymptomatic.

B. A pouch just above the lower esophageal sphincter is an epiphrenic diverticulum, a false pulsion pouch associated with achalasia or esophageal spasm.

D. Herniation through the esophageal hiatus is a hiatal hernia of the stomach, not a pharyngeal pouch.

E. Herniation through the thyrohyoid membrane produces a lateral pharyngeal pouch or laryngocele, which is anterolateral and much rarer.

Heavy daily drinking, hepatomegaly, an AST to ALT ratio above 2, and hepatocytes filled with a single large lipid vacuole that pushes the nucleus aside indicate macrovesicular hepatic steatosis, the earliest and reversible alcoholic liver lesion. Both steps of ethanol oxidation, alcohol dehydrogenase in the cytosol and aldehyde dehydrogenase in mitochondria, reduce NAD+ to NADH, so the hepatic NADH/NAD+ ratio rises sharply. Excess NADH drives the glycerol-3-phosphate dehydrogenase reaction toward reduction of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate, which supplies the backbone for esterifying fatty acids into triglycerides. At the same time, high NADH inhibits the NAD+-dependent steps of beta-oxidation and the TCA cycle, so fatty acids are esterified rather than burned. Triglyceride synthesis outpaces export as VLDL, and fat accumulates.

A and C are wrong because ethanol increases, not decreases, NADH; less beta-oxidation, not more, promotes fat accumulation, and hormone-sensitive lipase acts in adipose tissue rather than hepatocytes. B is wrong because high NADH pushes pyruvate toward lactate through lactate dehydrogenase, causing lactic acidosis and hyperuricemia, not toward alanine. E is wrong because ethanol lowers NAD+ availability and inhibits the TCA cycle, diverting acetyl-CoA to ketone bodies and fatty acid synthesis.

This patient has a second primary squamous cell carcinoma, not a recurrence. The clues are surrounding dysplasia in the adjacent esophageal mucosa (the tumor arose in place from a precursor lesion) and a TP53 mutation different from that of the first tumor (an independent clone). The explanation is field cancerization: tobacco smoke and alcohol bathe the whole upper aerodigestive tract, including the oral cavity, pharynx, larynx, esophagus and lung, and seed many independent mutated clones throughout that mucosa. A patient with one tobacco-related head and neck SCC therefore has a high risk of synchronous or later second primaries in the head and neck, esophagus or lung, which is why smoking cessation and lifelong surveillance are essential.

Tobacco-related head and neck SCCs occur in older adults, involve the oral cavity, larynx and hypopharynx, are p16-negative and characteristically carry TP53 mutations, as in this patient.

A. A metastasis would share the founding mutations of the primary tumor and would not arise from adjacent dysplastic mucosa. B. A germline TP53 mutation (Li-Fraumeni syndrome) would be present in every cell, so all tumors would share the same mutation, and it causes sarcomas, breast cancer, brain tumors and adrenocortical carcinoma at young ages. C. High-risk HPV drives oropharyngeal SCC in younger nonsmokers and produces p16-positive tumors; his first tumor was p16-negative and tobacco-related. D. Radiation for a floor-of-mouth tumor does not include the midesophagus, and radiation-induced cancers usually appear many years later, often as sarcomas.

This boy has Hartnup disease: a defective sodium-dependent neutral amino acid transporter in the intestine and proximal tubule causes neutral aminoaciduria and poor absorption of free tryptophan. Because tryptophan is a precursor for niacin synthesis, deficiency produces pellagra-like photosensitive dermatitis and cerebellar ataxia.

The defect affects only the uptake of free amino acids. Dietary protein is digested by pancreatic proteases and brush-border peptidases into a mixture of free amino acids and small peptides. Di- and tripeptides enter enterocytes through PepT1, an apical transporter driven by an inward H+ gradient rather than by Na+. Peptide uptake is actually faster than uptake of free amino acids, and once inside the cell the peptides are split by cytosolic peptidases, releasing tryptophan and other neutral amino acids, which then leave across the basolateral membrane into portal blood. A high-protein diet therefore bypasses the defective carrier, and nicotinamide treats the niacin deficit directly.

A is wrong because paracellular diffusion of amino acids is trivial and does not compensate for a transporter defect. B is wrong because basic amino acids (lysine, arginine, ornithine, cystine) use a separate carrier that does not move tryptophan; that carrier is defective in cystinuria. D is wrong because uptake of intact proteins is negligible in children and adults (it matters only for antibody transfer in some neonatal mammals). E is wrong because colonic bacteria do not supply meaningful absorbable tryptophan.

A traveler with resolved bloody dysentery followed by fever, right upper quadrant pain, and a single right-lobe liver lesion with positive serology has an amebic liver abscess. Trophozoites of Entamoeba histolytica invade the colonic mucosa, creating flask-shaped ulcers, and reach the liver through the portal vein, so the right lobe, which drains most of the right colon, is usually affected. Metronidazole is a prodrug reduced to DNA-damaging nitro radicals only by the low-redox ferredoxin-type carriers of anaerobes and protozoa; it is well absorbed and reaches tissue, so it kills invasive trophozoites and cures most abscesses without drainage. However, because it is absorbed high in the gut, it achieves poor concentrations in the colonic lumen and does not eliminate the cysts that remain there. Those cysts cause relapse and continued transmission, so every tissue-active course is followed by a luminal agent, paromomycin (a nonabsorbed aminoglycoside) or iodoquinol. Asymptomatic cyst passers receive the luminal agent alone.

A. Metronidazole penetrates tissue and abscesses well, which is precisely why most amebic abscesses resolve without drainage.

C. The disulfiram-like reaction comes from aldehyde dehydrogenase inhibition and is avoided by abstaining from alcohol; paromomycin does not prevent it.

D. Metronidazole has excellent activity against anaerobes such as Bacteroides fragilis, so this is the opposite of its gap.

E. Nitroimidazole resistance in tissue trophozoites is not the issue, and paromomycin is not absorbed, so it cannot treat tissue disease at all.