46 PEPTIC ULCER DISEASE

# PEPTIC ULCER DISEASE

What is a peptic ulcer?

A peptic ulcer is a focal breach of the mucosa that penetrates through the muscularis mucosae into the submucosa or deeper. This is the histological feature that distinguishes a true ulcer from an erosion, which is confined to the mucosa. The depth matters: ulcers can scar, perforate and erode into arteries, while erosions heal without consequence.

Peptic ulcers occur wherever mucosa is exposed to acid and pepsin. The two classic sites are the first part of the duodenum (D1) and the lesser curvature of the stomach, but ulcers can also arise in the lower oesophagus (reflux), the jejunum (Zollinger-Ellison) and within a Meckel's diverticulum containing ectopic gastric mucosa.

Pathophysiology: aggressors versus defenders

Peptic ulceration is fundamentally a breakdown in the balance between mucosal aggressors and mucosal defenders.

Aggressors	Defenders
Hydrochloric acid (parietal cells)	Mucus layer (surface mucous cells)
Pepsin (chief cells)	Bicarbonate secretion
H. pylori	Prostaglandins (PGE2, PGI2)
NSAIDs	Mucosal blood flow
Smoking	Rapid epithelial restitution
Alcohol, bile reflux	Tight junctions, cell turnover
Physiological stress (Cushing's, Curling's)

If aggressors win, the mucosa ulcerates. Most exam questions revolve around two aggressors — H. pylori and NSAIDs — and one defender — prostaglandins.

The role of prostaglandins

Prostaglandins are the central protective molecules of the gastric mucosa. They act on two distinct receptors:

➡ EP3 receptors on parietal cells ➡ decrease cAMP ➡ reduce HCl secretion

➡ EP2/EP4 receptors on surface mucous cells ➡ increase cAMP ➡ increase mucus and bicarbonate secretion

PGE2 and PGI2 also maintain mucosal blood flow, which is essential for clearing back-diffusing H⁺ ions and delivering bicarbonate. Anything that knocks out prostaglandin synthesis (NSAIDs blocking COX-1) removes all three layers of defence at once.

Helicobacter pylori

H. pylori is a Gram-negative, microaerophilic, spiral bacillus that colonises the gastric antrum. It is the single most common cause of peptic ulcer disease.

- Found in ~95% of duodenal ulcers

- Found in 70–80% of gastric ulcers

How it causes ulcers

H. pylori expresses urease, which splits urea into ammonia and CO₂. Ammonia neutralises gastric acid locally, allowing the organism to survive, and is directly cytotoxic to gastric epithelium. The bacterium also produces CagA and VacA virulence factors that damage epithelial tight junctions and trigger chronic inflammation.

Antral colonisation increases gastrin release (by inhibiting somatostatin from D cells), which drives parietal cells in the body of the stomach to secrete more acid. This excess acid reaches the duodenum, induces gastric metaplasia and creates the substrate for duodenal ulceration.

Diagnosis

The urease enzyme is exploited diagnostically:

- Urea breath test — patient drinks ¹³C-labelled urea; H. pylori urease releases ¹³CO₂, detected on exhalation. Non-invasive, good for confirming eradication.

- CLO (rapid urease) test — biopsy placed in urea-containing medium; colour change with ammonia. Performed at OGD.

- Stool antigen test — non-invasive alternative.

- Histology — gold standard; biopsy taken at OGD.

- Serology — confirms exposure but cannot distinguish current from past infection. Not useful post-eradication.

PPIs and antibiotics must be stopped before testing (PPI 2 weeks, antibiotics 4 weeks) — they suppress the organism and cause false negatives.

Eradication: triple therapy

UK first-line for 7 days:

➡ PPI (omeprazole/lansoprazole) twice daily

➡ Amoxicillin 1 g twice daily

➡ Clarithromycin 500 mg twice daily (or metronidazole if penicillin-allergic)

Eradication should be confirmed by urea breath test or stool antigen at least 4 weeks after completing therapy.

NSAID-induced ulcers

NSAIDs are the second great cause of peptic ulceration. They damage mucosa by two routes:

1. Topical injury — weak acids that diffuse into epithelial cells and become trapped.

2. Systemic inhibition of COX-1 — depleting protective prostaglandins (PGE2, PGI2). This is the dominant mechanism and is why even IV/PR NSAIDs cause ulcers.

COX-2 selective inhibitors (celecoxib) spare gastric COX-1 and carry a lower ulcer risk, but at the cost of increased cardiovascular events.

Misoprostol (a synthetic PGE1 analogue) can be co-prescribed for prophylaxis in high-risk patients but is poorly tolerated (diarrhoea, abortifacient). In practice a PPI is the standard gastroprotection alongside long-term NSAIDs.

Risk factors that should prompt gastroprotection: age > 65, previous ulcer, concurrent steroids/anticoagulants/SSRIs, high-dose or multiple NSAIDs.

Gastric versus duodenal ulcers

This is a classic comparison and a reliable source of SBA points.

Feature	Gastric ulcer	Duodenal ulcer
Typical site	Lesser curvature, antrum	D1 (first part)
Age	Older (> 50)	Younger (30–50)
H. pylori	70–80%	95%
Acid secretion	Normal or low	High
Pain and food	Worse with food (food + acid on raw mucosa)	Relieved by food, recurs 2–3 h later; classic night pain
Weight	Weight loss (avoids food)	Weight stable or gain
Malignancy risk	Significant — must biopsy	Negligible — biopsy not routine
Healing	Slower	Faster

👩‍⚕️ Every gastric ulcer must be biopsied at OGD and re-scoped at 6–8 weeks to confirm healing. A "gastric ulcer" that fails to heal is gastric cancer until proven otherwise. Duodenal ulcers do not require biopsy unless atypical.

Surgical anatomy you must know

The arterial supply of the stomach and duodenum dictates which ulcer bleeds from which vessel — high-yield exam material.

➡ Lesser curvature — left gastric artery (coeliac trunk) superiorly, right gastric artery (hepatic artery) inferiorly

➡ Greater curvature — left gastroepiploic (splenic) superiorly, right gastroepiploic (gastroduodenal) inferiorly

➡ Fundus — short gastric arteries (splenic)

➡ Posterior to D1 — gastroduodenal artery, a branch of the common hepatic

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Complications

Perforation

- Anterior D1 ulcer is the most common site to perforate — there is nothing posterior to retroperitonealise the leak, so gastric contents spill into the peritoneal cavity.

- Sudden, severe, generalised abdominal pain; rigid silent abdomen; signs of peritonitis and shock.

- Erect CXR is the first-line investigation, showing free air under the right hemidiaphragm in ~75% of cases.

- CT abdomen is the most sensitive (~98%) and is now standard if available; also excludes acute pancreatitis, which would not need surgery.

- Management: resuscitation, IV PPI, broad-spectrum antibiotics, urgent laparotomy/laparoscopy with omental (Graham) patch repair and peritoneal lavage. H. pylori eradication post-op.

Bleeding

- Posterior D1 ulcer is the classic bleeder, eroding into the gastroduodenal artery lying directly behind it.

- Lesser-curve gastric ulcers erode into the left gastric artery.

- Presents with haematemesis, coffee-ground vomiting and/or melaena.

- Resuscitate, transfuse, IV PPI, urgent OGD within 24 h.

- Endoscopic haemostasis uses dual therapy: adrenaline injection plus a second modality (thermal coagulation, clips, or haemostatic powder).

- If endoscopy fails: interventional radiology with GDA embolisation, then surgery (under-running of the ulcer) as last resort.

Gastric outlet obstruction

Chronic pre-pyloric or duodenal ulceration scars and stenoses the pylorus. Presents with projectile, non-bile-stained vomiting of undigested food, weight loss, succussion splash, and a hypochloraemic, hypokalaemic metabolic alkalosis with paradoxical aciduria. Treated with NG decompression, fluid resuscitation, IV PPI and either endoscopic balloon dilatation or surgery.

Penetration

The ulcer erodes through the full thickness of the wall into an adjacent organ — typically the pancreas (posterior duodenal ulcer) — without free perforation. Presents as a change in pain pattern: now constant, radiating to the back, no longer relieved by antacids. Raised amylase is a clue.

Risk stratification in upper GI bleeding

Two scores must be known.

➡ Glasgow-Blatchford score (GBS) — used at first contact, before endoscopy. Uses urea, haemoglobin, BP, pulse, melaena, syncope, hepatic disease, cardiac failure. A score of 0 allows safe outpatient management.

➡ Rockall score — combines pre- and post-endoscopy variables (age, shock, comorbidity, diagnosis at OGD, stigmata of recent haemorrhage). Predicts rebleeding and mortality.

👩‍⚕️ Easy exam mark: GBS = pre-endoscopy, decides admission. Rockall = post-endoscopy, predicts outcome.

Investigations summary

- OGD with biopsy — gold standard for diagnosis; allows therapeutic intervention; mandatory for gastric ulcers to exclude malignancy.

- **H. pylori testing** — urea breath test, CLO at OGD, stool antigen.

- Erect CXR / CT for suspected perforation.

- FBC, U&Es, group and save/crossmatch, clotting, LFTs for bleeding.

- Fasting gastrin if multiple/refractory/jejunal ulcers — think Zollinger-Ellison syndrome (gastrinoma, often in the duodenal wall or pancreas, part of MEN-1).

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Test yourself

A patient on long-term NSAIDs develops haematemesis. What is the mechanism by which aspirin contributes to gastric ulcers?

• ((Inhibition of prostaglandin synthesis::☑️ COX-1 blockade depletes PGE2, removing mucus, bicarbonate and mucosal blood flow.))
• ((Inhibition of somatostatin::Somatostatin inhibits acid; aspirin has no effect on its release.))
• ((Inhibition of gastrin::Gastrin secretion is unaffected by NSAIDs.))
• ((Inhibition of secretin::Secretin drives pancreatic bicarbonate, unrelated to NSAID injury.))
• ((Inhibition of cholecystokinin::CCK governs gallbladder and pancreatic enzyme release.))

👩‍⚕️ COX-1 is the protective isoform in the stomach; COX-2 selectives spare it but raise cardiovascular risk.

A patient is bleeding from an anterior gastric ulcer between the antrum and body of the stomach. Where is the source of the bleeding?

• ((Short gastric arteries::Supply the fundus from the splenic artery.))
• ((Left gastroepiploic::Supplies the upper greater curvature.))
• ((Right gastroepiploic::Supplies the lower greater curvature near the antrum.))
• ((Left gastric artery::☑️ Lesser curvature between antrum and body is left gastric territory.))

A patient has a posterior perforating duodenal ulcer that is bleeding. Which artery is most likely injured?

• ((Right hepatic artery::Runs in the hepatoduodenal ligament, not posterior to D1.))
• ((Left gastric artery::Supplies the lesser curvature, not the duodenum.))
• ((Left gastroepiploic::Runs along the greater curvature.))
• ((Gastroduodenal artery::☑️ Lies directly posterior to D1 — the classic bleeder.))
• ((Right gastroepiploic::A distal branch of the GDA along the greater curve, not posterior to D1.))

Endoscopy shows bleeding from a deep posterior ulcer in the first part of the duodenum. Which vessel is responsible?

• ((Gastroduodenal artery::☑️ D1 sits anterior to the GDA; posterior ulcers erode straight into it.))
• ((Left gastric artery::Supplies the lesser curve of the stomach.))
• ((Superior mesenteric artery::Lies behind the pancreatic neck, not D1.))
• ((Right gastric artery::Runs along the lesser curve, not the duodenum.))

A 45-year-old man on chronic NSAIDs presents with sudden severe abdominal pain and suspected perforated duodenal ulcer. Which investigation is most accurate for detecting free intra-abdominal air?

• ((CT abdomen::☑️ ~98% sensitive for pneumoperitoneum; also rules out pancreatitis.))
• ((Erect CXR::Best first-line investigation but lower sensitivity than CT.))
• ((Abdominal ultrasound::Air scatters the beam — unreliable for pneumoperitoneum.))
• ((Supine AXR::Free air is rarely visible on a supine film.))

👩‍⚕️ Phrasing matters: "most accurate" = CT; "first-line/initial" = erect CXR.

A 35-year-old pregnant woman presents with acute abdominal pain and suspected perforated duodenal ulcer. What is the best initial investigation?

• ((Erect CXR::☑️ Low fetal radiation dose; acceptable if clinically indicated to find free air.))
• ((CT abdomen::Avoided in pregnancy unless essential due to higher radiation.))
• ((Abdominal ultrasound::Cannot reliably detect pneumoperitoneum.))
• ((Diagnostic peritoneal lavage::Invasive and obsolete in this setting.))

A 45-year-old man with chronic NSAID use presents with severe abdominal pain and suspected perforation. What is the best first-line investigation for free air?

• ((Erect CXR::☑️ Standard initial investigation — free air under the diaphragm.))
• ((Supine AXR::Free air is difficult to see on supine films.))
• ((Abdominal ultrasound::Unreliable for pneumoperitoneum.))
• ((Lateral decubitus X-ray::Can show air but erect CXR remains first-line.))

Which test is most appropriate to confirm successful H. pylori eradication 6 weeks after triple therapy?

• ((Urea breath test::☑️ Non-invasive, detects active infection, ideal for confirming eradication.))
• ((Serology::Antibodies persist after clearance — cannot prove eradication.))
• ((CLO test::Requires repeat OGD — invasive and unnecessary.))
• ((Stool culture::H. pylori is fastidious and not routinely cultured.))

A patient with chronic duodenal ulceration presents with projectile non-bilious vomiting and weight loss. What acid-base disturbance is expected?

• ((Hypochloraemic hypokalaemic metabolic alkalosis::☑️ Loss of gastric HCl and K⁺ from prolonged vomiting in gastric outlet obstruction.))
• ((Metabolic acidosis with raised anion gap::Suggests sepsis, ischaemia or DKA — not pyloric stenosis.))
• ((Respiratory alkalosis::Seen in hyperventilation, not vomiting.))
• ((Normal anion gap acidosis::Pattern of diarrhoea or RTA, not vomiting.))

Which score is used at first contact, before endoscopy, to decide whether a patient with upper GI bleeding can be managed as an outpatient?

• ((Glasgow-Blatchford score::☑️ Pre-endoscopy; a score of 0 allows safe outpatient management.))
• ((Rockall score::Combines pre- and post-endoscopy data; predicts rebleeding/mortality.))
• ((Child-Pugh score::Assesses chronic liver disease severity.))
• ((MELD score::Prognostic in liver disease and transplant listing.))

A duodenal ulcer biopsy is sent for rapid urease (CLO) testing. What enzyme reaction underpins the test?

• ((Urease splits urea into ammonia and CO₂::☑️ Ammonia raises pH and changes the indicator colour.))
• ((Catalase breaks down hydrogen peroxide::Used to differentiate staphylococci, not H. pylori.))
• ((Oxidase reaction::Distinguishes Pseudomonas and Neisseria species.))
• ((Coagulase activity::Identifies Staphylococcus aureus.))

Revision summary

➡ Peptic ulcer = mucosal defect through the muscularis mucosae; commonest at D1 and lesser curve.

➡ Pathogenesis = aggressors (acid, pepsin, H. pylori, NSAIDs, smoking) overwhelming defenders (mucus, bicarbonate, prostaglandins, blood flow).

➡ H. pylori — 95% of DU, 70–80% of GU; urease-positive; triple therapy = PPI + amoxicillin + clarithromycin for 7 days.

➡ NSAIDs damage via COX-1 inhibition → loss of protective PGE2; PPI cover for high-risk patients.

➡ Gastric ulcer = pain worse with food, weight loss, must biopsy. Duodenal ulcer = pain relieved by food, night pain, biopsy not routine.

➡ Anterior D1 ulcer ➡ perforates (free gas, peritonitis).

➡ Posterior D1 ulcer ➡ bleeds from gastroduodenal artery.

➡ Lesser curve gastric ulcer ➡ bleeds from left gastric artery.

➡ Free air detection — erect CXR is first-line, CT most sensitive (use CXR in pregnancy).

➡ Gastric outlet obstruction ➡ hypochloraemic hypokalaemic metabolic alkalosis with paradoxical aciduria.

➡ Glasgow-Blatchford = pre-OGD (admit or not). Rockall = post-OGD (predicts rebleed/mortality).

➡ Refractory or multiple ulcers ➡ check fasting gastrin (Zollinger-Ellison, MEN-1).