Ulkus Peptikum & Duodenum

01Pathophysiology

Peptic ulcer disease results from an imbalance between aggressive factors (gastric acid, pepsin, H. pylori, NSAIDs) and protective factors (mucus-bicarbonate barrier, prostaglandins, mucosal blood flow, epithelial cell renewal). When the aggressive forces overwhelm the defense mechanisms, the gastric or duodenal mucosa erodes beyond the muscularis mucosae, forming a true ulcer.

Helicobacter pylori is a gram-negative, spiral-shaped, urease-producing bacterium that colonizes the gastric antrum. It survives in the acidic gastric environment by producing urease, which converts urea into ammonia and $C{O}_{2}CO\_2$, creating a local alkaline microenvironment. The organism triggers a chronic inflammatory response with neutrophilic and lymphocytic infiltration, damaging the epithelium. In the duodenum, H. pylori-driven antral gastritis leads to increased gastrin release from G cells, which stimulates parietal cell acid production. This excess acid load in the duodenal bulb causes gastric metaplasia of the duodenal epithelium, which H. pylori then colonizes, perpetuating the cycle of injury. This is why duodenal ulcers are strongly associated with increased acid secretion.

In contrast, gastric ulcers are more often associated with decreased mucosal defense rather than acid hypersecretion. H. pylori infection of the gastric body (corpus) causes atrophic gastritis and loss of parietal cells, reducing acid output but simultaneously weakening the mucosal barrier.

NSAIDs cause ulcers through inhibition of cyclooxygenase-1 (COX-1), the enzyme responsible for producing prostaglandins $PG{E}_{2}PGE\_2$ and $PG{I}_{2}PGI\_2$. These prostaglandins stimulate mucus and bicarbonate secretion, promote mucosal blood flow, and support epithelial cell turnover. When prostaglandin synthesis is blocked, the mucosa loses its protective coating and becomes vulnerable to acid-peptic injury. Importantly, NSAID ulcers are often painless and may present first with a complication such as bleeding or perforation, because the same prostaglandin inhibition that damages the mucosa also blunts pain signaling.

The location of the ulcer determines the clinical presentation. Duodenal ulcers cause pain that improves with food because eating stimulates bicarbonate secretion and buffers the acidic chyme. The pain returns 2 to 3 hours later when the buffering effect wears off and acid re-accumulates ("hunger pain"). Gastric ulcers worsen with eating because food stimulates acid secretion directly against the damaged gastric mucosa, with no buffering intermediary.

The most feared complications relate directly to the depth of ulcer penetration. Erosion into a blood vessel (especially the gastroduodenal artery for posterior duodenal ulcers) causes hemorrhage. Erosion through the full wall thickness causes perforation, typically presenting with acute peritonitis and free air. Chronic inflammation and scarring of the pyloric channel or duodenal bulb lead to gastric outlet obstruction, presenting with postprandial vomiting of undigested food and a succussion splash on exam.

02Classification and Clinical Manifestation

Ulcer Type by Location

Complication-Based Classification

Modified Johnson Classification of Gastric Ulcers

03Diagnostic Workup

The diagnostic approach hinges on two critical decisions: whether to scope the patient, and how to test for H. pylori.

For patients under 60 years old without alarm features (unintentional weight loss, dysphagia, persistent vomiting, GI bleeding, anemia, palpable mass, family history of upper GI malignancy), the best initial strategy is a noninvasive "test-and-treat" approach. Order a urea breath test or stool antigen test. If positive for H. pylori, treat with eradication therapy. If negative and the patient is on NSAIDs, discontinue the offending medication and start empiric PPI therapy.

For patients 60 years or older, or those with any alarm feature, the best initial step is upper endoscopy (EGD). This allows direct visualization of the ulcer, biopsy for histopathology (to rule out gastric adenocarcinoma), and biopsy-based H. pylori testing via the rapid urease test. All gastric ulcers require biopsy because gastric adenocarcinoma can mimic a benign ulcer endoscopically. Duodenal ulcers almost never harbor malignancy and do not routinely require biopsy for cancer, though biopsy for H. pylori is still recommended.

When testing for eradication of H. pylori after treatment, use the urea breath test or stool antigen test at least 4 weeks after completing antibiotics and 1 to 2 weeks after stopping PPI therapy. PPIs and antibiotics suppress bacterial load and can cause false negatives. Serology is never used to confirm eradication because IgG antibodies persist for months to years after successful treatment.

For refractory ulcers that do not heal after 8 to 12 weeks of appropriate therapy, consider Zollinger-Ellison syndrome (gastrinoma). The initial screening test is a fasting serum gastrin level (markedly elevated, typically greater than 1000 pg/mL). The confirmatory test is the secretin stimulation test: administer IV secretin, then measure gastrin levels. In gastrinoma, gastrin paradoxically rises by more than 120 pg/mL above baseline (normal stomach would show suppression or no change). Localize the tumor with CT, MRI, or somatostatin receptor scintigraphy.

04Management and Treatment

Acute stabilization always takes priority. For a patient presenting with signs of upper GI bleeding (hematemesis, melena, dropping hemoglobin, tachycardia, hypotension), the immediate steps are: secure IV access with two large-bore IVs, aggressive fluid resuscitation, type and crossmatch for transfusion, and start an IV PPI drip. The target for transfusion is generally a hemoglobin threshold of 7 g/dL in hemodynamically stable patients without cardiovascular disease. EGD should be performed within 24 hours of presentation; in hemodynamically unstable patients or those with ongoing active bleeding, perform EGD emergently after resuscitation.

Endoscopic findings guide further management. High-risk stigmata on EGD include active arterial spurting (Forrest Ia), oozing (Forrest Ib), a visible vessel (Forrest IIa), and an adherent clot (Forrest IIb). These findings require endoscopic intervention. A clean-based ulcer (Forrest III) or flat pigmented spot (Forrest IIc) can be managed medically without endoscopic treatment.

Long-term management centers on healing the ulcer and preventing recurrence. After completing H. pylori eradication therapy, continue PPI monotherapy for 4 weeks (duodenal ulcers) or 8 weeks (gastric ulcers) to ensure complete mucosal healing. Confirm eradication with a urea breath test or stool antigen test at least 4 weeks after completing antibiotics and 1 to 2 weeks off PPIs.

For patients who must remain on NSAIDs (for example, patients with rheumatoid arthritis), the strategy is to use the lowest effective dose of a COX-2 selective inhibitor (celecoxib) combined with a PPI for gastroprotection. Misoprostol (a prostaglandin $PG{E}_{1}PGE\_1$ analog, 200 mcg QID) is an alternative mucosal protectant, but its use is limited by side effects (diarrhea, abdominal cramping) and it is absolutely contraindicated in pregnancy because it causes uterine contractions and can induce abortion.

For gastric ulcers, repeat EGD at 8 to 12 weeks is recommended to document healing and re-biopsy the ulcer site to definitively rule out malignancy. This follow-up endoscopy is not routinely required for duodenal ulcers.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common way students lose points on peptic ulcer questions is by confusing the meal-pain relationship. Duodenal ulcer pain improves with eating and returns hours later; gastric ulcer pain worsens with eating. The vignette will describe the timing carefully, and the answer choices will include both types. Read the temporal relationship closely.

A second frequent trap involves posterior versus anterior duodenal ulcers. Posterior ulcers bleed (gastroduodenal artery), while anterior ulcers perforate (into the peritoneal cavity). When the vignette describes sudden severe abdominal pain with peritonitis and free air on X-ray, think anterior perforation. When it describes hematemesis, melena, and hemodynamic instability, think posterior bleeding. The examiners test this anatomy-complication pairing consistently.

Students also frequently miss the requirement for repeat endoscopy in gastric ulcers but not duodenal ulcers. A gastric ulcer can harbor cancer, so you must re-scope at 8 to 12 weeks to confirm healing and re-biopsy. A duodenal ulcer is almost never malignant, so follow-up EGD is unnecessary.

Another high-yield point is the false-negative pitfall in H. pylori testing. If a patient has been on PPIs, bismuth, or antibiotics within the past 2 to 4 weeks, noninvasive tests (urea breath test, stool antigen) may be falsely negative. The vignette may describe a patient who "just completed a course of antibiotics" or is "on omeprazole." If you see this, recognize that the negative test result may not be reliable.

Finally, watch for the Zollinger-Ellison setup: a patient with refractory ulcers despite adequate PPI therapy, ulcers in atypical locations, or ulcers associated with secretory diarrhea. The next step is a fasting serum gastrin level. These vignettes are designed to test whether you can recognize the failure of standard therapy as a diagnostic clue rather than simply escalating the PPI dose.

The core competency being tested across peptic ulcer questions is the ability to integrate clinical context (age, medication history, alarm features) into a stepwise diagnostic and management algorithm, rather than reflexively ordering the same test for every patient with epigastric pain.