see also:

• epigastric pain
• Dyspepsia
• EMedicine

• Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa.
• Western society has a 10% lifetime prevalence of developing PUD.
• Under normal conditions, a physiologic balance exists between peptic acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted.
• Aggressive factors allowing back diffusion of hydrogen ions and subsequent epithelial cell injury and include NSAIDs, H pylori, alcohol, bile salts, acid, and pepsin.
• The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.

• genetic factors:
  • European ethnicities tend to have DUs while Japanese tend to have GUs
  • a 2023 study identified 25 new areas on the genome (raising total loci to 33) associated with peptic ulcers and also identified the association of PUD with certain hormone-secreting cells, including stomach D cells (somatostatin) and stomach antral and duodenal EC cells (5-HT) and demonstrated that, besides HP-related loci, host genetic factors potentially involved in gastric hormone regulation, cell differentiation and proliferation might play important roles in PUD pathogenesis¹⁾
• 90% of DU's & 2/3rds of GU's are due to interplay between genetics, mucosal damage by Helicobacter pylori and luminal acid
  • Untreated, ulcer disease runs a chronic relapsing course characterised by periodic episodes of pain and the risk of complications including bleeding and perforation.
• most of the remaining 1/3rd of GU's are due to non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin (acetylsalicylic acid)
  • non-steroidal anti-inflammatory drugs (NSAIDs)
    • About 15% to 30% of NSAID users will have ulcers at endoscopy but many of these may be clinically silent until complications such as bleeding, anaemia or perforation occur.
    • The relative risk of a serious gastrointestinal adverse event with NSAIDs varies between drugs and is also dose-related.
    • NSAIDs with a longer duration of action (longer half-life) are more likely to cause serious gastrointestinal complications.
    • The risk is also related to other patient-specific risk factors such as age, co-morbidity, past ulcer disease, smoking and concomitant medication (eg antiplatelet agents, anticoagulants and corticosteroids).
  • Low-dose aspirin (acetylsalicylic acid) use increases the risk of peptic ulcer.
    • About 1 in 10 chronic users will have an ulcer at endoscopy although most will not have symptoms.
    • Aspirin increases the risk of bleeding (odds ratio 1.6).
    • A past history of ulcer, current H. pylori infection or concurrent NSAID use markedly increases this risk.
    • The risk is dose-dependent and not reduced by enteric-coated or buffered aspirin.
    • data suggests that PPI prophylaxis with continued aspirin use is less likely to cause recurrent bleeding than a switch to clopidogrel.
    • Australian Prescriber 2005: aspirin, alcohol & GIT bleeding
  • NB. Corticosteroids alone do not increase the risk for PUD, however, they can potentiate the ulcer risk in patients who use NSAIDs concurrently.
• Other less common causes are hypersecretory states, such as:
  • Zollinger-Ellison syndrome
  • G-cell hyperplasia
  • mastocytosis
  • basophilic leukemias.

• mainly an issue in intensive care units in critically ill patients
• risk factors:
  • sepsis &/or shock
  • hypotension
  • acidosis
  • peritonitis
  • head injury

• severe acute bleeding results in haematemesis
  • The mortality from acute peptic ulcer bleeding has not changed materially in recent years and remains at 7% to 10% despite advances in patient management.
• more chronic bleeding may cause iron deficient anaemia

• Ulcer penetration refers to penetration of the ulcer through the bowel wall without free perforation and leakage of luminal contents into the peritoneal cavity.
• Surgical series suggest that penetration occurs in 20 percent of ulcers, but only a small proportion of penetrating ulcers become clinically evident.
• Penetration occurs in descending order of frequency into the pancreas, gastrohepatic omentum, biliary tract, liver, greater omentum, mesocolon, colon, and vascular structures.
• The change in symptom pattern may be gradual or sudden; it usually involves a loss of cyclicity of the pain with meals, and loss of food and antacid relief. The pain typically becomes more intense, of longer duration, and is frequently referred to the lower thoracic or upper lumbar region.
• serum amylase may be raised mildy but clinical pancreatitis is uncommon
• may cause uncommon complications such as:
  • erosion into vascular structures leading to exsanguinating hemorrhage (aortoenteric fistula)
  • perivisceral abscess
  • erosion into the cystic artery
  • Rare biliary tract complications include erosion into the biliary tree with choledochoduodenal fistula, extra hepatic obstruction, or hematobilia.

• Duodenal, antral, and gastric body ulcers account for 60, 20 and 20 percent of perforations due to peptic ulcer, respectively.
• One-third to one-half of perforated ulcers are associated with NSAID use; these usually occur in elderly patients
• see perforated viscus

• the least frequent major ulcer complication

• proton pump inhibitors (PPIs) are superior to histamine H2-receptor antagonists for healing ulcers.
• In uncomplicated duodenal ulcer disease, Helicobacter pylori eradication therapy is usually all that is required.
• For all complicated ulcers, large gastric ulcers, ulcers occurring in high-risk patients or ulcers associated with NSAID use, ongoing antisecretory therapy with a proton pump inhibitor (PPI) for about 8 weeks is appropriate. This maximises the likelihood of ulcer healing, particularly in patients destined to remain infected after eradication therapy.

• acute healing:=
  • 6-8 weeks course of PPI
    • stop smoking
  • NB. proton pump inhibitors are effective but more expensive
• after ulcer healed then Helicobacter pylori eradication therapy
• maintenance Rx if Helicobacter eradication therapy not attempted or unsuccessful:
  • nocte dose PPI

• as for DU but:
  • PPI bd dosing not once daily
  • acute therapy should be 2-4weeks longer than for DU, depending on ulcer size
  • exclude NSAID aetiology as cause before embarking on Helicobacter eradication therapy

• Ther. Guidelines
• test for & Rx with Helicobacter pylori eradication therapy
• avoid NSAIDs if possible - even COX-2 inhibitors may cause ulcers
• if ongoing NSAID Rx is needed and the risk of ulceration is outweighed by benefits of NSAIDS then either
  • COX-2 inhibitor, or
  • NSAID + prophylactic PPI (eg. omeprazole 20mg/d)

• prophylaxis:=
  • ranitidine 50mg slow IV or 2hr infusion 6-8h, or,
  • famotidine 20mg IV over 30min 12h, or,
  • sucralfate 1g (crushed tablets, or suspension) via NGT every 6h

• see upper GI bleeding

• a surgical emergency
• diagnosis usually on finding of free air under the diaphragm in a patient with likely PUD and examination findings of peritonitis
• IV fluid resuscitation
• triple iv antibiotics as per surgeon's preference
• emergent surgical repair within ASAP
• see perforated viscus

• Aust Presc 2008 - Long-term management of patients taking proton pump inhibitors