A 32-year-old man comes to the clinic for peptic ulcer disease follow-up. The patient has received several months of proton pump inhibitor therapy without significant improvement in his epigastric discomfort. He does not use nonsteroidal anti-inflammatory drugs, tobacco, or alcohol. Helicobacter pylori testing is negative. The patient undergoes a partial gastrectomy for refractory peptic ulcer disease. The pathologist receives the tissue and notes significant enlargement of the gastric rugal folds on gross examination. Microscopy of the gastric mucosa reveals parietal cell hyperplasia. Which of the following stimuli is the most likely cause of parietal cell proliferation in this patient?

Question

A 32-year-old man comes to the clinic for peptic ulcer disease follow-up.  The patient has received several months of proton pump inhibitor therapy without significant improvement in his epigastric discomfort.  He does not use nonsteroidal anti-inflammatory drugs, tobacco, or alcohol.  Helicobacter pylori testing is negative.  The patient undergoes a partial gastrectomy for refractory peptic ulcer disease.  The pathologist receives the tissue and notes significant enlargement of the gastric rugal folds on gross examination.  Microscopy of the gastric mucosa reveals parietal cell hyperplasia.  Which of the following stimuli is the most likely cause of parietal cell proliferation in this patient?

Quizplus · Accepted Answer

Parietal cells are located in the gastric glands of the fundus and body of the stomach. They can be spotted easily due to their eosinophilic cytoplasm on H&E stain. These cells have abundant mitochondria and an intracellular tubulovesicular system that allows them to secrete large quantities of gastric acid (HCl) and intrinsic factor. Parietal cells are influenced by a number of substances. Histamine, acetylcholine, and gastrin increase gastric acid secretion, but prostaglandins inhibit it. Gastrin not only stimulates HCl secretion, but it also has a trophic effect on parietal cells. In patients with Zollinger-Ellison syndrome (such as this patient), gastrin hypersecretion induces parietal cell hyperplasia, causing visible enlargement of gastric folds on endoscopy. The increased gastric acid secretion induced by excess gastrin also causes peptic ulcer disease, heartburn, and diarrhea. (Choice A) Acetylcholine is a universal neurotransmitter that is present in parasympathetic postganglionic synapses and in all autonomic preganglionic synapses. Cholinergic receptors are divided into muscarinic (located in smooth muscle and glands) and nicotinic (found at the neuromuscular junction). Acetylcholine stimulates parietal cell acid secretion but is not typically associated with parietal cell hyperplasia or gastric fold enlargement. (Choice C) Secretin is produced by S cells of the small intestine. It increases bicarbonate production by the pancreas and leads to the secretion of watery, alkaline pancreatic juice. This substance also inhibits gastric acid secretion and stimulates pyloric sphincter contraction. (Choice D) Serotonin (5HT) is primarily found in enterochromaffin cells of the gastrointestinal (GI) tract, the central nervous system, and platelets. In the GI tract, it helps to regulate intestinal secretions and peristalsis. (Choice E) Somatostatin (growth hormone-inhibiting hormone) is secreted by D cells of pancreatic islets and GI mucosa. It has multiple inhibitory effects over the GI tract, including decreasing motility, gastrin secretion, pancreatic endocrine/exocrine secretion, and absorption of nutrients. (Choice F) Transforming growth factor alpha (TGF-α) is a potent stimulator of epithelial growth and is secreted by carcinomas, macrophages, and epithelial cells. Menetrier disease is associated with overproduction of TGF-α, resulting in mucosal-cell hyperplasia with gastric fold enlargement. However, the condition causes hypoplasia of parietal/chief cells, resulting in glandular atrophy with reduced gastric acid secretion. Educational objective: Patients with Zollinger-Ellison syndrome develop peptic ulcer disease and parietal cell hyperplasia with gastric fold enlargement due to gastrin hypersecretion. __________ References: Zollinger-Ellison Syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/12628075) Role of gastrointestinal hormones in the proliferation of normal and neoplastic tissues. (http://www.ncbi.nlm.nih.gov/pubmed/14570743)

A 32-Year-Old Man Comes to the Clinic for Peptic Ulcer