Peptic Ulcer Disease: H. pylori, NSAIDs & Gastrinoma

Creator: Progress Note
Published: 2026-05-19
Keywords: peptic ulcer disease treatment H pylori, peptic ulcer disease usmle, h pylori urease, gastric vs duodenal ulcer, gastroduodenal artery ulcer, zollinger ellison secretin, autoimmune gastritis type a, curling vs cushing ulcer, misoprostol, bismuth quadruple therapy

bolt The 60-second version

check_circleMucosal defense: mucus, bicarbonate, blood flow, and prostaglandins (PGE₂). Ulcers form when injury outweighs defense.
check_circleH. pylori: curved, flagellated, gram-negative, urease-positive rod; it colonizes the antrum and raises gastrin, increasing duodenal acid load.
check_circleNSAIDs inhibit COX-1 → less prostaglandin → less mucus, bicarbonate, and mucosal blood flow.
check_circleDuodenal ulcer pain improves with meals (weight gain); gastric ulcer pain worsens with meals (weight loss). Gastric ulcers are biopsied to exclude cancer.
check_circlePosterior duodenal ulcers can erode the gastroduodenal artery; lesser-curvature gastric ulcers can erode the left gastric artery. Anterior ulcers perforate → free air under the diaphragm.
check_circleGastrinoma (Zollinger-Ellison syndrome): multiple or refractory ulcers, ulcers beyond the duodenal bulb, diarrhea; associated with MEN1; gastrin rises paradoxically with secretin.

target What you'll be able to do · aligned to USMLE Step 1 · Gastrointestinal

MICRODescribe H. pylori virulence, associated diseases, testing, and eradication therapy.
PHARMExplain how NSAIDs cause ulcers and how misoprostol, bismuth, and acid suppressants treat them.
PATHCompare gastric and duodenal ulcers and autoimmune vs H. pylori gastritis.
ANATPredict bleeding vessels and perforation from ulcer location, and recognize gastrinoma.

How PUD is tested on Step 1

Vignettes give epigastric pain related to meals, an NSAID or H. pylori clue, or a complication such as bleeding or perforation.

Causes. Curling ulcers follow severe burns (hypovolemia → mucosal ischemia); Cushing ulcers follow raised intracranial pressure (vagal stimulation → ↑ acid).

Gastric vs duodenal. Duodenal ulcers are more common.

Helicobacter pylori

The microbe behind most ulcers and two gastric cancers.

Microbiology: curved, flagellated, gram-negative rod; urease converts urea to ammonia, buffering acid around the organism.
Diseases: chronic antral gastritis, duodenal and gastric ulcers, gastric adenocarcinoma (intestinal type), and MALT lymphoma.
Testing: urea breath test or stool antigen (both show active infection); biopsy at endoscopy. Serology cannot confirm eradication.
Treatment: bismuth quadruple therapy (PPI, bismuth, metronidazole, tetracycline) or a clarithromycin-based triple regimen (PPI, clarithromycin, amoxicillin) where resistance is low; confirm eradication afterward.

Gastritis	Location	Cause and consequences
Type A (autoimmune)	Body and fundus	Antibodies to parietal cells and intrinsic factor → achlorhydria, pernicious anemia, ↑ gastrin; risk of carcinoid and adenocarcinoma
Type B (H. pylori)	Antrum first	Most common; ulcers, adenocarcinoma, MALT lymphoma
Acute erosive	Variable	NSAIDs, alcohol, burns, shock, uremia

Memory aid: type A = Autoimmune and Anemia; type B = Bacteria.

Complications

Location predicts the complication.

Where it bleeds or breaks. Perforation causes sudden severe pain, a rigid abdomen, free air under the diaphragm, and sometimes shoulder pain from diaphragmatic irritation.

Gastrinoma and ulcer drugs

Know when ulcers are not ordinary.

Zollinger-Ellison syndrome: gastrin-secreting tumor (duodenum or pancreas, in the "gastrinoma triangle"); refractory or multiple ulcers, jejunal ulcers, diarrhea (acid inactivates pancreatic enzymes). Elevated fasting gastrin with low gastric pH; secretin stimulation paradoxically increases gastrin. About one-quarter are part of MEN1.
Misoprostol: PGE₁ analog that restores mucosal protection in NSAID users; causes diarrhea and is contraindicated in pregnancy (uterine contractions).
Bismuth: coats ulcers and is antibacterial against H. pylori; can blacken the stool and tongue.
PPIs and H₂ blockers: heal ulcers by suppressing acid; PPIs are more potent.

Worked example

Match the bleed to the artery.

functions Worked example — sudden hematemesis

A 50-year-old with months of epigastric pain that improves after eating now vomits blood and becomes hypotensive. Endoscopy shows an ulcer on the posterior wall of the duodenal bulb with a visible vessel. Which artery is bleeding, and which organism is likely responsible?

Pain relieved by food suggests a duodenal ulcer.
The gastroduodenal artery runs behind the first part of the duodenum.
A posterior duodenal ulcer can erode into it, causing major hemorrhage.
Duodenal ulcers are most strongly associated with H. pylori.

Answer. Gastroduodenal artery bleeding from a posterior duodenal ulcer, most likely caused by H. pylori.

Next in the roadmap

GI Bleeding

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2 real questions on Peptic Ulcer Disease

Straight from the Progress Note question bank, each with a cited explanation. No account needed.

A 68-year-old man with a long-standing peptic ulcer perforation undergoes emergency surgical exploration. An endoscopic image is shown below. Histology of the specimen shows necrotic, acellular material at the ulcer base with surrounding chronic inflammatory infiltrate (lymphocytes, plasma cells, macrophages). Which of the following best explains why the ulcer base contains primarily chronic inflammation rather than acute inflammation, and how this pattern reflects the natural history of chronic peptic ulcer disease?

Image for question 1 — DSamir_grover, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

A 58-year-old woman with chronic dyspepsia undergoes upper endoscopy. Biopsy of a gastric antral lesion reveals a dense lymphoid infiltrate with lymphoepithelial lesions, CD20-positive B cells, and curved bacilli on Giemsa stain consistent with Helicobacter pylori. The biopsy was stained with Bcl-2, shown below. FISH performed on the biopsy is positive for t(11;18) resulting in the API2-MALT1 fusion transcript. The patient undergoes successful H. pylori eradication therapy, confirmed by a negative urea breath test. Which outcome is most likely on follow-up gastric biopsy?

Image for question 2 — TexasPathologistMSW, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

Frequently asked questions

Why do NSAIDs cause ulcers?expand_more

They inhibit COX-1, lowering prostaglandins that maintain mucus, bicarbonate secretion, and mucosal blood flow.

Which gastric cancers are linked to H. pylori?expand_more

Intestinal-type gastric adenocarcinoma and MALT lymphoma.

Which artery bleeds from a posterior duodenal ulcer?expand_more

The gastroduodenal artery.

How is a gastrinoma confirmed?expand_more

A high fasting gastrin level with low gastric pH; gastrin rises further after secretin stimulation (it falls in normal G cells).

References & further reading

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