Basic Science/ Pathophysiology
Which of the following is the most common cause of gastroesophageal reflux disease (GERD)?
A) Hypotensive lower esophageal sphincter (LES)
B) Esophageal motility disorder
C) Overproduction of gastric acid
D) Hiatal hernia
Answer: A) Hypotensive lower esophageal sphincter (LES)
The most common cause of GERD is a hypotensive LES, which allows gastric contents, including acid, to reflux into the esophagus.
What is the most common histological change observed in Barrett's esophagus?
A) Columnar metaplasia
B) Squamous metaplasia
C) Dysplasia of the squamous epithelium
D) Hyperkeratosis
Answer: A) Columnar metaplasia
In Barrett's esophagus, there is a transformation of the normal squamous epithelium of the esophagus to columnar epithelium, which is a type of metaplasia in response to chronic acid exposure.
A 58-year-old man with a history of NSTEMI is on dual antiplatelet therapy. He develops GERD and is prescribed a new medication. A week later, he presents with chest pain and is found to have stent thrombosis. Which of the following drugs most likely contributed to this adverse event?
A. Famotidine
B. Pantoprazole
C. Omeprazole
D. Calcium carbonate
C. Omeprazole
Omeprazole is a CYP450 inhibitor, reducing clopidogrel activation, increasing thrombosis risk.
Which of the following GERD medications has no interaction with the cytochrome P450 system?
A. Omeprazole
B. Ranitidine
C. Famotidine
D. Calcium Carbonate
D. Calcium Carbonate
Which of the following complications is Barrett’s esophagus most strongly associated with?
A. Esophageal stricture
B. Squamous cell carcinoma of the esophagus
C. Erosive esophagitis
D. Esophageal adenocarcinoma
D. Esophageal adenocarcinoma
Which of the following factors is most commonly associated with GERD in patients with a hiatal hernia?
A) Decreased gastric acid secretion
B) Increased intra-abdominal pressure
C) Increased LES tone
D) Reduced esophageal motility
Answer: B) Increased intra-abdominal pressure
Explanation: Hiatal hernia often leads to increased intra-abdominal pressure, which pushes the stomach upward and causes LES dysfunction, contributing to GERD.
Which of the following is a common finding in a patient with Barrett's esophagus on endoscopy?
A) Irregular, ulcerated areas in the esophagus
B) A salmon-colored mucosa in the distal esophagus
C) A smooth, white mucosal appearance
D) A prominent Schatzki ring
Answer: B) A salmon-colored mucosa in the distal esophagus
Explanation: Barrett's esophagus typically presents with a salmon-colored mucosa in the distal esophagus due to the columnar metaplasia.
A 60-year-old patient with renal failure should avoid which of the following for GERD treatment?
A. Famotidine
B. Magnesium hydroxide
C. Ranitidine
D. Sucralfate
should avoid which of the following for GERD treatment?
B. Magnesium hydroxide
The primary mechanism by which PPIs reduce acid secretion involves:
A. Competitive inhibition of the H2 receptor on parietal cells
B. Irreversible blockade of the Na+/K+ ATPase
C. Irreversible inactivation of the H+/K+ ATPase
D. Blocking carbonic anhydrase in gastric mucosa
C. Irreversible inactivation of the H+/K+ ATPase
What is the hallmark histological finding in Barrett's esophagus?
A. Stratified squamous epithelium with keratin pearls
B. Simple cuboidal epithelium with Paneth cells
C. Nonciliated columnar epithelium with goblet cells
D. Pseudostratified columnar epithelium with cilia
C. Nonciliated columnar epithelium with goblet cells
In the pathophysiology of GERD, which of the following contributes most to esophageal acid clearance?
A) Increased LES pressure
B) Esophageal peristalsis
C) Gastric acid production
D) Saliva production
Answer: B) Esophageal peristalsis
Explanation: Esophageal peristalsis is critical for acid clearance from the esophagus, pushing refluxed material back into the stomach.
In GERD, what mechanism leads to transient LES relaxations (TLESRs)?
A) Decreased vagal tone
B) Increased sympathetic nervous system activity
C) Impaired gastric emptying
D) Inappropriate relaxation of the LES in response to swallowing or other stimuli
Answer: D) Inappropriate relaxation of the LES in response to swallowing or other stimuli
Explanation: TLESRs are an inappropriate and transient relaxation of the LES, often triggered by swallowing, that allows gastric contents to reflux into the esophagus.
Which of the following mechanisms is shared by both caffeine and alcohol in promoting reflux?
A. Direct mucosal damage to the esophageal lining
B. Inhibition of bicarbonate production
C. Inhibition of esophageal peristalsis
D. Decrease in lower esophageal sphincter tone
D. Decrease in lower esophageal sphincter tone
The two main forms of esophageal cancer are __________ and ___________.
Esophageal adenocarcinoma and Esophageal squamous cell carcinoma.
Which of the following physical exam findings is most commonly associated with GERD?
A. Rebound tenderness in the right lower quadrant
B. Epigastric tenderness
C. Distended abdomen with guarding
D. Murphy’s sign
B. Epigastric tenderness
A patient is found to have excessive gastric acid secretion due to a tumor. A biopsy of the stomach shows parietal cell hyperplasia. Which of the following intracellular signaling pathways is most likely upregulated?
A) cAMP-PKA pathway
B) IP3-DAG pathway
C) JAK-STAT pathway
D) MAP kinase pathway
Answer: B) IP3-DAG pathway
Explanation: Gastrin stimulates parietal cells via the CCK-B receptor, which works through the IP3-DAG pathway, leading to an increase in intracellular calcium and activation of H⁺ secretion. Histamine works via the cAMP-PKA pathway, while the others are not directly relevant to gastric acid secretion.
A 54-year-old man with a history of GERD presents with progressive dysphagia to both solids and liquids. Esophageal manometry shows a loss of peristalsis in the distal esophagus and incomplete relaxation of the lower esophageal sphincter. Which of the following best explains this patient’s presentation?
A) Myenteric plexus destruction
B) Fibrosis of the submucosa
C) Metaplasia of the squamous epithelium
D) Hypertrophy of the esophageal muscularis propria
Answer: A) Myenteric plexus destruction
Explanation: Chronic GERD can lead to achalasia-like features due to chronic inflammation affecting the myenteric (Auerbach’s) plexus, which impairs esophageal peristalsis and LES relaxation. This differs from classic achalasia, which is caused by idiopathic or Chagas disease-related plexus degeneration.
Prokinetics like metoclopramide can be considered in GERD patients:
A. With erosive esophagitis
B. With partial response to PPIs
C. With constipation
D. Who are pregnant
B. With partial response to PPIs
Which of the following is a long-term risk associated with H2 receptor antagonists in elderly patients?
A. Hypercalcemia
B. CNS effects like delirium
C. Gastric ulcer
D. Metabolic alkalosis
B. CNS effects like delirium
Which of the following findings on EGD is most suggestive of Barrett esophagus?
A. Mucosal friability
B. Erythema in the esophagus
C. Proximal migration of the Z line with salmon pink mucosa
D. Esophageal ulcerations
C. Proximal migration of the Z line with salmon pink mucosa
A patient with a long history of GERD undergoes esophageal biopsy, which reveals elongation of lamina propria papillae, basal cell hyperplasia, and intraepithelial eosinophils. Which of the following best explains these findings?
A) Chronic acid exposure causing squamous epithelial metaplasia
B) An allergic response resulting in eosinophilic infiltration
C) Hyperplastic response to repeated mucosal injury
D) Malignant transformation of esophageal epithelium
Answer: C) Hyperplastic response to repeated mucosal injury
Explanation: GERD leads to chronic mucosal irritation, resulting in basal cell hyperplasia, elongation of lamina propria papillae, and intraepithelial eosinophils, which are classic histologic features of reflux esophagitis. This precedes Barrett’s esophagus but does not yet involve metaplasia.
A 60-year-old man with GERD undergoes an endoscopy that reveals salmon-colored mucosa in the distal esophagus. Biopsy confirms specialized intestinal metaplasia. Which of the following molecular changes is most likely present?
A) Upregulation of TP53
B) Overexpression of CDX2
C) Downregulation of SOX9
D) Mutation in SMAD4
Answer: B) Overexpression of CDX2
Explanation: Barrett’s esophagus occurs due to chronic acid exposure, leading to columnar intestinal metaplasia, which is driven by CDX2, a transcription factor promoting intestinal differentiation. TP53 mutations occur later in Barrett’s-associated adenocarcinoma, while SMAD4 is linked to pancreatic cancer.
Which of the following best explains why tolerance develops to H2 blockers?
A. Enzyme induction of cytochrome P450
B. Upregulation of proton pumps in parietal cells
C. Desensitization of histamine H2 receptors
D. Compensatory increase in gastrin secretion
D. Compensatory increase in gastrin secretion
Chronic acid suppression → increased gastrin → acid rebound and tolerance.
A 67-year-old woman with type 2 diabetes mellitus and chronic gastroparesis presents with involuntary facial grimacing and repetitive tongue protrusion. Her symptoms have progressed over the last 3 months. She denies recent changes in medication but mentions she’s been taking a medication to help with her stomach emptying for “many years.” Neurological exam reveals choreoathetoid movements of the face and upper limbs. MRI of the brain is unremarkable.
Which of the following best explains the pathophysiology of her current symptoms?
A. Dopamine receptor hypersensitivity in the basal ganglia due to chronic D2 antagonism
B. Glutamate excitotoxicity in the substantia nigra due to NMDA receptor overstimulation
C. Loss of dopaminergic neurons in the nigrostriatal pathway due to autoimmunity
D. Serotonin excess in the mesolimbic system leading to extrapyramidal symptoms
E. Acute cholinergic excess in the cerebellum secondary to anticholinesterase overdose
A. Dopamine receptor hypersensitivity in the basal ganglia due to chronic D2 antagonism
- Metoclopramide is a D2 receptor antagonist used for gastroparesis and GERD.
- Chronic blockade of dopamine D2 receptors leads to receptor upregulation and hypersensitivity → this can manifest as tardive dyskinesia, a late-onset, often irreversible movement disorder.
- Tardive dyskinesia is characterized by involuntary, repetitive movements such as tongue protrusion, lip smacking, and facial grimacing.
- Elderly patients and those on long-term therapy are at higher risk.
Which of the following patients is the most appropriate candidate for early EGD prior to initiating proton pump inhibitor (PPI) therapy?
A. A 32-year-old woman with classic heartburn and regurgitation but no alarm symptoms.
B. A 55-year-old man with longstanding GERD symptoms who improves partially with over-the-counter antacids.
C. A 28-year-old man with hoarseness and chronic cough but no dysphagia or weight loss.
D. A 45-year-old woman with heartburn and unintentional 10-kg weight loss over two months.
D. A 45-year-old woman with heartburn and unintentional 10-kg weight loss over two months.