Peptic Ulcer Disease

Article Author:
Talia Malik
Article Author:
Karthik Gnanapandithan
Article Editor:
Kevin Singh
3/25/2020 4:39:16 PM
PubMed Link:
Peptic Ulcer Disease


Peptic ulcer disease (PUD) is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. Epigastric pain usually occurs within 15-30 minutes following a meal in patients with a gastric ulcer; on the other hand, the pain with a duodenal ulcer tends to occur 2-3 hours after a meal. Today, testing for Helicobacter pylori is recommended in all patients with peptic ulcer disease. Endoscopy may be required in some patients to confirm the diagnosis, especially in those patients with sinister symptoms. Today, most patients can be managed with a proton pump inhibitor (PPI) based triple-drug therapy.


Peptic ulcer disease (PUD) has various causes; however, Helicobacter pylori-associated PUD and NSAID-associated PUD account for the majority of the disease etiology.[1]

Causes of Peptic Ulcer Disease


  • H. pylori infection
  • NSAIDs
  • Medications


  • Zollinger-Ellison syndrome
  • Malignancy (gastric/lung cancer, lymphomas)
  • Stress (Acute illness, burns, head injury)
  • Viral infection
  • Vascular insufficiency
  • Radiation therapy
  • Crohn disease
  • Chemotherapy

Helicobacter Pylori-Associated PUD

H. pylorus is a gram-negative bacillus that is found within the gastric epithelial cells. This bacterium is responsible for 90% of duodenal ulcers and 70% to 90% of gastric ulcers. H. pylori infection is more prevalent among those with lower socioeconomic status and is commonly acquired during childhood. The organism has a wide spectrum of virulence factors allowing it to adhere to and inflame the gastric mucosa. This results in hypochlorhydria or achlorhydria, leading to gastric ulceration.

 Virulence Factors of  Helicobacter pylori

  1. Urease: The secretion of urease breaks down urea into ammonia and protects the organism by neutralizing the acidic gastric environment.
  2. Toxins: CagA/VacA is associated with stomach mucosal inflammation and host tissue damage.
  3. Flagella: Provides motility and allows movement toward the gastric epithelium.

NSAID-associated PUD

Nonsteroidal anti-inflammatory drugs use is the second most common cause of PUD after H. pylori infection.[2][3] The secretion of prostaglandin normally protects the gastric mucosa. NSAIDs block prostaglandin synthesis by inhibiting COX-1 enzyme resulting in a decrease in gastric mucus and bicarbonate production and a decrease in mucosal blood flow.


Apart from NSAIDs, corticosteroids, bisphosphonates, potassium chloride, steroids, and fluorouracil have been implicated in the etiology of PUD.

Smoking also appears to play a role in duodenal ulcers, but the correlation is not linear. Alcohol can irritate the gastric mucosa and induce acidity.

Hypersecretory environments

  • Zollinger Ellison syndrome
  • Systemic mastocytosis
  • Cystic fibrosis
  • Hyperparathyroidism
  • Antral G cell hyperplasia


PUD is a global problem with a lifetime risk of development ranging from 5% to 10%.[4][5] Overall, there is a decrease in the incidence of PUD worldwide due to improved hygienic and sanitary conditions combined with effective treatment and judicious use of NSAIDs.[5] Duodenal ulcers are four times more common than gastric ulcers. Also, duodenal ulcers are more common in men than in the woman.


The mechanism of occurrence of PUD results from an imbalance between gastric mucosal protective and destructive factors. Risk factors predisposing to the development of PUD:

  • H. pylori infection
  • NSAID use
  • First-degree relative with PUD
  • Emigrant from a developed nation
  • African American/Hispanic ethnicity

With peptic ulcers, there is usually a defect in the mucosa that extends to the muscularis mucosa. Once the protective superficial mucosal layer is damaged, the inner layers are susceptible to acidity. Further, the ability of the mucosal cells to secrete bicarbonate is compromised.

H. pylori is known to colonize the gastric mucosa and causes inflammation. The H. pylori also impairs the secretion of bicarbonate, promoting the development of acidity and gastric metaplasia.


Gastric ulcers are most commonly located on the lesser curvature, whereas duodenal ulcers are most common at the duodenal bulb. The ulcer is round to oval with a smooth base. Acute ulcers have regular borders, while chronic ulcers have elevated borders with inflammation. An ulcer extends beyond the muscularis mucosa.

History and Physical

Signs and symptoms of peptic ulcer disease may vary depending upon the location of the disease and age. Gastric and duodenal ulcers can be differentiated from the timing of their symptoms in relation to meals. Nocturnal pain is common with duodenal ulcers. Those with gastric outlet obstruction commonly report a history of abdomen bloating and or fullness.

Common signs and symptoms include:

  • Epigastric abdominal pain
  • Bloating
  • Abdominal fullness
  • Nausea and vomiting
  • Weight loss/weight gain
  • Hematemesis
  • Melena

Warning symptoms that should prompt urgent referral include:

  • Weight loss
  • Progressive dysphagia
  • Significant anemia
  • Recurrent emesis


Diagnosis of PUD requires history taking, physical examination, and invasive/noninvasive medical tests.


A careful history should be obtained and noted for the presence of any complications. Patient reporting of epigastric abdominal pain, early satiety, and fullness following a meal raise suspicion of PUD. The pain of gastric ulcers increases 2 to 3 hours after a meal and may result in weight loss, whereas the pain of duodenal ulcers decreases with meal resulting in weight gain. Any patient presenting with anemia, melena, hematemesis, or weight loss should be further investigated for complications of PUD, predominantly bleeding, perforation, or cancer.

Physical Exam

A physical exam may reveal epigastric abdominal tenderness and signs of anemia.


  1. Esophagogastroduodenoscopy (EGD): Gold standard and most accurate diagnostic test with sensitivity and specificity up to 90% in diagnosing gastric and duodenal ulcers.
  2. Barium swallow: It is indicated when EGD is contraindicated.
  3. Complete blood work, liver function, and levels of amylase and lipase
  4. Serum gastric is ordered if Zollinger Ellison syndrome is suspected
  5. Helicobacter pylori testing:
  • Serologic testing
  • Urea breath test: High sensitivity and specificity. It may be used to confirm eradication after 4 to 6 weeks of stopping treatment. In the presence of urease, an enzyme produced by H.pylori, the radiolabeled carbon dioxide produced by the stomach is exhaled by the lungs.
  • Antibodies to H.pylori can also be measured
  • Stool antigen test
  • Urine-based ELISA and rapid urine test
  • Endoscopic biopsy: Culture is not generally recommended as it is expensive, time-consuming, and invasive. It is indicated if eradication treatment fails or there is suspicion about antibiotic resistance. Biopsies from at least 4-6 sites are necessary to increase sensitivity. Gastric ulcers are commonly located on the lesser curvature between the antrum and fundus. The majority of duodenal ulcers are located in the first part of the duodenum.

Imaging is done if perforation is suspected. Barium studies may show extravasation of the contrast.

Treatment / Management


Antisecretory drugs used for PUD include H2-receptor antagonists and the proton pump inhibitor (PPIs). PPIs have largely replaced H2 receptor blockers due to their superior healing and efficacy. PPIs block acid production in the stomach, providing relief of symptoms and promote healing. Treatment may be incorporated with calcium supplements as long-term use of the PPIs can increase the risk of bone fractures. NSAIDs induced PUD can be treated by stopping the use of NSAIDs or switching to a lower dose. Corticosteroid, bisphosphonates, and anticoagulants should also be discontinued if possible. Prostaglandin analogs (misoprostol) are sometimes used as prophylaxis for NSAID-induced peptic ulcers. First-line treatment for H. pylori-induced PUD is a triple regimen comprising two antibiotics and a proton pump inhibitor. Pantoprazole, clarithromycin, and metronidazole or amoxicillin are used for 7 to 14 days.[6] Antibiotics and PPIs work synergistically to eradicate H. pylori.[7] The antibiotic selected should take into consideration the presence of antibiotic resistance in the environment. If first-line therapy fails, the change the antibiotics and use quadruple therapy with bismuth.


Surgical treatment is indicated if the patient is unresponsive to medical treatment, noncompliant, or at high risk of complications. Surgical options include vagotomy or partial gastrectomy.

Differential Diagnosis

  • Gastritis
  • Pancreatitis
  • Gastroesophageal reflux disease (GERD)
  • Cholecystitis
  • Stomach cancer
  • Biliary colic
  • Myocardial infarction (inferior)
  • Referred pain


The prognosis of PUD is excellent after the underlying cause is successfully treated. Recurrence of the ulcer may be prevented by maintaining good hygiene and avoiding alcohol, smoking, and NSAIDs. Unfortunately, recurrence is common wth rates exceeding 60% in most series. NSAID induced gastric perforation occurs at a rate of 0.3% per patient per year. However, unlike the past, mortality rates for peptic ulcer disease have decreased significantly.


  • Bleeding
  • Gastric outlet obstruction
  • Perforation
  • Penetration
  • Stomach cancer


Once a diagnosis of peptic ulcer disease is made, consult with a gastroenterologist and dietician.

Deterrence and Patient Education

  • Avoid prolonged and unnecessary use of NSAIDs
  • Use the lowest dose of NSAID that is effective
  • Consider prophylaxis for patients who use NSAIDs

Pearls and Other Issues

Ulcers are differentiated from erosions based on size. Lesions less than 5 mm in diameter are termed erosions, whereas lesions greater than 5 mm in diameter are termed ulcers. COX-2 selective NSAIDs are less likely to cause PUD as COX-2 is not expressed on the gastric mucosa. Therefore, in patients with a history of PUD, COX-2 selective NSAIDs are preferred.

A gastrin-producing endocrine tumor causes Zollinger-Ellison syndrome. It usually arises from the pancreas or duodenum. It results in multiple ulcers in the duodenum and jejunum. It can be diagnosed by measuring serum gastrin levels.

Enhancing Healthcare Team Outcomes

An evidence-based approach to peptic ulcer disease is recommended.  PUD is a very common disorder that affects millions of people. When left untreated, it has significant morbidity. The majority of patients with PUD present to their primary caregiver, but others may present to the emergency department, urgent care clinic, or an outpatient clinic. Because the presentation of PUD is often vague, healthcare workers, including nurses, need to be aware of this diagnosis. The abdominal pain can mimic a number of other pathologies and consequently lead to a delay in treatment.

Once the diagnosis is made, the key is to educate the patient on lifestyle changes, which include discontinuation of smoking, abstaining from alcohol and caffeinated beverages, and avoid consumptions of too many NSAIDs. Gastroenterology nurses monitor patients, provide education, and keep the team updated on the patient's condition. The pharmacist should educate the patient on medication compliance to obtain symptom relief and a cure. A dietary consult should be sought as there is evidence that obesity may be a trigger factor for peptic ulcer disease. Only through a team approach can the morbidity of peptic ulcer disease be decreased.


For most patients with PUD who are treated with the triple regimen or PPI, the outcomes are excellent, but recurrence of symptoms is not uncommon.[8][9] (Level 2)


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