Peptic Ulcer Disease

Peptic ulcer disease (PUD) is a mucosal break ≥5 mm in the stomach or duodenum penetrating the muscularis mucosae, arising from an imbalance between aggressive factors (acid, pepsin, H. pylori, NSAIDs) and mucosal defence (mucus–bicarbonate layer, prostaglandins, blood flow). It is one of the most heavily examined GIT topics in NEET PG — H. pylori diagnostics, the duodenal-versus-gastric distinction, eradication regimens, and complications recur every year.

Definition & classification

A peptic ulcer is a defect that breaches the muscularis mucosae; this distinguishes it from an erosion, which is superficial and confined to the mucosa (erosions do not scar). Ulcers are classified by site:

• Duodenal ulcer (DU) — commonest, 4× more frequent than gastric ulcer; >95% in the first part (D1, duodenal bulb); almost always benign.
• Gastric ulcer (GU) — classically along the lesser curvature at the incisura angularis (junction of body and antrum); 2–4% risk of malignancy, so always biopsied.

The modified Johnson classification of gastric ulcers is high-yield:

Type	Location	Acid status	Mechanism
I	Lesser curve / incisura (commonest GU)	Low/normal	Defective mucosal defence
II	Body of stomach + duodenal ulcer	High	Acid hypersecretion
III	Prepyloric / pyloric channel	High	Acid hypersecretion (NSAID-like behaviour)
IV	High on lesser curve near GE junction	Low/normal	Mucosal defence defect
V	Anywhere	Variable	NSAID/drug-induced (diffuse)

High-yield: Types II and III gastric ulcers are associated with acid hypersecretion (behave like duodenal ulcers); Types I and IV are not.

Etiology & pathophysiology

The two dominant causes are Helicobacter pylori and NSAIDs; together they account for the vast majority of ulcers.

1. Helicobacter pylori (Gram-negative, microaerophilic, spiral, urease-positive).

• Present in ~90–95% of duodenal ulcers and ~70–80% of gastric ulcers.
• Survives gastric acid by producing urease, which splits urea into ammonia + CO₂, creating an alkaline microenvironment — this is the basis of the rapid urease (CLO) test and urea breath test.
• Antral-predominant gastritis → increased gastrin → increased acid → duodenal ulcer.
• Body/corpus-predominant (pangastritis) → mucosal atrophy, hypochlorhydria → gastric ulcer, gastric atrophy, intestinal metaplasia → gastric adenocarcinoma & MALT lymphoma.
• Virulence factors: CagA and VacA (vacuolating cytotoxin) correlate with more severe disease.

High-yield: H. pylori is a WHO Group 1 (definite) carcinogen — linked to gastric adenocarcinoma and gastric MALT lymphoma (which can regress with eradication alone in early disease).

2. NSAIDs/aspirin.

• Inhibit COX-1 → reduced mucosal prostaglandins (PGE₂, PGI₂) → loss of mucus/bicarbonate, reduced mucosal blood flow.
• Cause gastric ulcers > duodenal ulcers (reverse of H. pylori), often in the antrum, frequently silent until they bleed.

3. Zollinger–Ellison syndrome (ZES) — gastrin-secreting tumour (gastrinoma) driving massive acid output; covered below.

Other contributors: smoking (delays healing, raises recurrence), severe physiological stress (Cushing/Curling ulcers), corticosteroids (synergistic with NSAIDs), and rarely viral (CMV/HSV in immunocompromised).

Pathophysiology flow (duodenal ulcer): H. pylori antral colonisation → ↓ somatostatin from D-cells → ↑ gastrin from G-cells → ↑ parietal cell acid output → duodenal mucosal injury + gastric metaplasia in duodenum → H. pylori colonises metaplastic patches → ulcer.

Clinical features

• Epigastric pain (dyspepsia) is the cardinal symptom — gnawing or burning.
• Duodenal ulcer: pain relieved by food/antacids, occurs 2–5 h after meals and classically at night (11 pm–2 am) when acid output peaks; "hunger pain." Patients may gain weight.
• Gastric ulcer: pain worsened by food (food-provoked), so patients fear eating and lose weight; pain less predictable.

Feature	Duodenal ulcer	Gastric ulcer
Relative frequency	More common (4:1)	Less common
Age	Younger (25–50)	Older (>50)
Acid secretion	Normal/high	Normal/low
Pain vs food	Relieved by food	Worsened by food
Night pain / hunger pain	Typical	Less typical
Weight	Maintained/gain	Loss
Malignant potential	Negligible	2–4% — always biopsy
Blood group association	O	A
H. pylori positivity	~90–95%	~70–80%

High-yield mnemonic: "Duodenal — Decreases with Dinner; Gastric — Greater with Grub." Eating relieves a Duodenal ulcer and aggravates a Gastric ulcer.

Alarm ("red flag") features mandating prompt endoscopy: age >55 with new dyspepsia, weight loss, anaemia/GI bleeding (melena, haematemesis), dysphagia, persistent vomiting, palpable mass, or family history of GI cancer.

Diagnosis & investigation of choice

Upper GI endoscopy (OGD) is the gold-standard investigation — it visualises the ulcer, permits biopsy, and allows therapeutic haemostasis. Every gastric ulcer must be biopsied (multiple edge biopsies) to exclude malignancy, and re-scoped at 6–8 weeks to confirm healing. Duodenal ulcers, being almost never malignant, do not routinely require biopsy.

Testing for H. pylori

Test	Type	Key point
Rapid urease / CLO test	Invasive (biopsy)	Fast, done at endoscopy; detects urease activity
Histology (biopsy, Giemsa/Warthin-Starry)	Invasive	Allows assessment of gastritis/metaplasia
Culture	Invasive	Gold standard for antibiotic sensitivity; slow, low yield
¹³C-Urea breath test (UBT)	Non-invasive	Best for confirming eradication; high sensitivity & specificity
Stool antigen test	Non-invasive	Useful for diagnosis and confirming cure
Serology (IgG antibody)	Non-invasive (blood)	Cannot distinguish current vs past infection; stays positive after cure — not for follow-up

High-yield: PPIs, bismuth, and antibiotics cause false-negative urease-based tests (UBT, CLO) and stool antigen. Stop PPIs for 2 weeks and antibiotics/bismuth for 4 weeks before testing. Serology is unaffected by these drugs.

High-yield: Urea breath test is the investigation of choice to confirm eradication, performed ≥4 weeks after completing therapy.

Other tests: Fasting serum gastrin if ZES suspected; secretin stimulation test (paradoxical rise in gastrin confirms gastrinoma). Barium meal (now largely obsolete) may show ulcer crater with radiating folds.

Management & drug of choice

Eradication of H. pylori (test-and-treat for all H. pylori-positive ulcers)

Standard triple therapy (14 days preferred):

PPI (e.g. omeprazole/pantoprazole, twice daily) + Amoxicillin 1 g BD + Clarithromycin 500 mg BD

• Use metronidazole in place of amoxicillin in penicillin allergy.
• Avoid clarithromycin-based triple therapy where clarithromycin resistance >15% — in such regions (including much of India), use bismuth-based quadruple therapy.

Bismuth quadruple therapy (10–14 days): PPI + Bismuth subsalicylate + Metronidazole + Tetracycline — preferred where macrolide resistance is high or after triple-therapy failure.

High-yield: Mnemonic for triple therapy — "PAC" = PPI + Amoxicillin + Clarithromycin.

Eradication management flow:

1. Diagnose ulcer (endoscopy) and test for H. pylori.
2. If positive → give 14-day eradication regimen.
3. Confirm eradication with UBT or stool antigen ≥4 weeks later (off PPI ≥2 weeks).
4. Gastric ulcers → repeat endoscopy at 6–8 weeks to confirm healing and exclude cancer.
5. Continue PPI for 4–8 weeks total (longer for GU) for ulcer healing.

Acid suppression & supportive measures

• PPIs are the most potent acid suppressants and first-line for healing; H₂-blockers (ranitidine, famotidine) are weaker alternatives.
• Stop NSAIDs; if NSAIDs are unavoidable, use the lowest dose + co-prescribe a PPI or switch to a COX-2 selective agent (with cardiovascular caution).
• Misoprostol (PGE₁ analogue) prevents NSAID ulcers but causes diarrhoea and is abortifacient (contraindicated in pregnancy).
• Stop smoking and alcohol; the role of diet is minor.
• Sucralfate (cytoprotective, needs acid to activate) and antacids are adjuncts.

High-yield: In an NSAID user who is H. pylori-positive with an ulcer, you must both eradicate H. pylori and stop the NSAID/add a PPI — eradication alone is insufficient.

Surgery (rarely needed now)

Reserved for complications or refractory disease. Classic operations: highly selective (proximal gastric) vagotomy (lowest dumping, higher recurrence), truncal vagotomy + drainage (pyloroplasty), and antrectomy + vagotomy (lowest recurrence, highest morbidity). Graham omental patch closure is used for perforated DU.

Complications

The four classic complications — Bleeding, Perforation, Obstruction (gastric outlet), Penetration.

1. Bleeding — most common complication.

• Presents as haematemesis and/or melena; the bleeding vessel in posterior DU is the gastroduodenal artery.
• Forrest classification stratifies rebleeding risk at endoscopy:

Forrest class	Endoscopic finding	Rebleed risk
Ia	Spurting arterial bleed	Highest
Ib	Oozing bleed	High
IIa	Non-bleeding visible vessel	High
IIb	Adherent clot	Intermediate
IIc	Flat pigmented spot	Low
III	Clean ulcer base	Lowest

• Management: resuscitate → IV PPI infusion → endoscopic haemostasis (injection adrenaline + a second modality: thermal/clips — dual therapy) → angioembolisation or surgery if it fails.

High-yield: Bleeding is the commonest complication of PUD; a posterior duodenal ulcer eroding the gastroduodenal artery is the classic cause of brisk upper-GI haemorrhage.

2. Perforation.

• Sudden severe pain, board-like rigidity, signs of peritonitis; erect chest/abdominal X-ray shows free gas under the diaphragm (pneumoperitoneum).
• Commonest site of perforation = anterior wall of the first part of the duodenum. (Posterior DU tends to bleed; anterior DU tends to perforate.)

High-yield: Perforation site is most often the duodenum (anterior D1); the haemorrhage from posterior D1 erodes the gastroduodenal artery. Distinguish anterior = perforate vs posterior = bleed.

3. Gastric outlet obstruction (pyloric stenosis).

• From chronic prepyloric/pyloric ulcers; succussion splash, projectile non-bilious vomiting, and hypochloraemic hypokalaemic metabolic alkalosis with paradoxical aciduria.

4. Penetration — ulcer erodes into adjacent organ (e.g. posterior DU into pancreas → pain radiating to back, raised amylase).

5. Malignancy — gastric ulcers may harbour or progress to adenocarcinoma; hence mandatory biopsy and follow-up.

Zollinger–Ellison syndrome (gastrinoma)

A non-β islet cell gastrin-secreting tumour, usually in the "gastrinoma triangle" (bounded by the cystic duct, junction of 2nd/3rd parts of duodenum, and neck/body of pancreas).

• Features: multiple/refractory/atypical-site ulcers (distal duodenum, jejunum), severe peptic disease, and secretory diarrhoea/steatorrhoea (acid inactivates pancreatic lipase).
• ~20–25% are part of MEN-1 (parathyroid + pituitary + pancreas — the "3 Ps").
• Diagnosis: markedly raised fasting serum gastrin + low gastric pH; secretin stimulation test shows a paradoxical rise in gastrin (normal gastrin falls). Localise with somatostatin-receptor scintigraphy / Ga-68 DOTATATE PET / EUS.
• Treatment: high-dose PPIs to control acid; surgical resection of the tumour where feasible.

High-yield: Suspect ZES with multiple ulcers, ulcers distal to the duodenal bulb, ulcers refractory to therapy, or ulcers with diarrhoea — confirm with fasting gastrin + secretin stimulation test.

Key differentials

• Functional (non-ulcer) dyspepsia — dyspepsia with normal endoscopy (commonest cause of dyspepsia overall).
• GORD — retrosternal burning, regurgitation, worse on lying down.
• Gastric carcinoma — weight loss, anaemia, Virchow's node; a non-healing gastric ulcer is cancer until proven otherwise.
• Acute coronary syndrome (inferior MI) — epigastric pain mimicking ulcer; do an ECG in older patients.
• Biliary colic / cholecystitis — right hypochondrial, post-fatty-meal pain.
• Acute pancreatitis — epigastric pain radiating to back, raised lipase.
• Gastritis / erosions — superficial, do not breach muscularis mucosae.

Recently asked / exam angle

• Urease test basis — H. pylori produces urease → splits urea → ammonia (CLO test, urea breath test). Very frequently asked.
• Best test to confirm eradication = urea breath test (not serology, which stays positive).
• PPI causes false-negative urease-based and stool antigen tests — stop 2 weeks prior.
• Triple therapy components = PPI + amoxicillin + clarithromycin (PAC).
• Commonest complication = bleeding; commonest perforation site = anterior duodenum; gastroduodenal artery is the bleeder in posterior DU.
• Duodenal ulcer pain relieved by food; gastric ulcer pain aggravated by food.
• Gastric ulcer mandates biopsy (malignancy risk); duodenal ulcer does not.
• Modified Johnson type II & III GU = acid hypersecretion.
• ZES — secretin stimulation test, MEN-1 association, gastrinoma triangle.
• Blood group O ↔ duodenal ulcer; blood group A ↔ gastric ulcer/Ca stomach.
• H. pylori — WHO Group 1 carcinogen, MALT lymphoma regresses with eradication.

Rapid revision

1. Peptic ulcer = mucosal break ≥5 mm breaching the muscularis mucosae; erosions are superficial.
2. Duodenal ulcers are 4× commoner than gastric and almost always benign.
3. Duodenal: pain relieved by food, night/hunger pain; Gastric: pain worsened by food, weight loss.
4. H. pylori uses urease to survive acid — basis of CLO test & urea breath test.
5. Antral gastritis → ↑ gastrin → duodenal ulcer; corpus gastritis → atrophy → gastric ulcer/cancer.
6. NSAIDs inhibit COX-1 → ↓ prostaglandins → gastric ulcers (silent, bleed-prone).
7. Endoscopy is the gold standard; every gastric ulcer must be biopsied and re-scoped at 6–8 weeks.
8. Urea breath test confirms eradication ≥4 weeks post-therapy; serology cannot (stays positive).
9. Triple therapy = PPI + Amoxicillin + Clarithromycin (PAC); use bismuth quadruple therapy where clarithromycin resistance is high.
10. Bleeding = commonest complication; gastroduodenal artery bleeds in posterior DU; Forrest Ia = highest rebleed risk.
11. Perforation commonest at anterior D1; erect X-ray shows gas under the diaphragm.
12. ZES = gastrinoma (gastrinoma triangle, MEN-1, secretin stimulation test); H. pylori is a WHO class 1 carcinogen causing gastric MALT lymphoma.