Q1 LONG ANSWER 10M ★ High-yield

Define peptic ulcer. Describe its aetiology, pathogenesis, morphology and complications. Differentiate benign from malignant gastric ulcer.

Pathology · 2nd Professional — Para-Clinical

Definition

A peptic ulcer is a breach in the mucosa of the alimentary tract extending through the muscularis mucosae, produced by the action of acid and pepsin.

An erosion does not breach the muscularis mucosae; an ulcer does — which is why erosions heal without scarring and ulcers do not
Sites — first part of the duodenum (commonest), stomach (lesser curvature, antrum), gastro-oesophageal junction, gastrojejunostomy stoma, and a MECKEL diverticulum containing ectopic gastric mucosa
Duodenal ulcers are about four times commoner than gastric

Aetiology

Factor	Mechanism
Helicobacter pylori	Present in 90% of duodenal and 70% of gastric ulcers. A gram-negative, curved, urease-producing organism. Urease splits urea to ammonia, neutralising acid locally and allowing it to survive; also produces cytotoxins (CagA, VacA), proteases and phospholipases
NSAIDs and aspirin	Inhibit COX-1, so mucosal prostaglandin synthesis falls — less mucus, less bicarbonate, less blood flow. The commonest cause of H. Pylori-negative ulcers
Zollinger–ellison syndrome	A gastrinoma causing massive acid hypersecretion; multiple ulcers in unusual sites such as the jejunum, resistant to treatment; associated with men 1
Smoking	Impairs healing and mucosal blood flow
Corticosteroids	Impair healing; act synergistically with NSAIDs
Physiological stress	Curling ulcer — after severe burns. Cushing ulcer — with raised intracranial pressure, from vagal stimulation of acid secretion
Other	Alcohol, chronic obstructive pulmonary disease, cirrhosis, chronic renal failure, hyperparathyroidism

Pathogenesis

Ulceration reflects an imbalance between aggressive and defensive factors → aggressive — acid, pepsin, H. Pylori, NSAIDs, bile reflux → defensive — surface mucus, bicarbonate, epithelial barrier and rapid regeneration, mucosal blood flow, prostaglandins → In duodenal ulcer: H. Pylori antral gastritis → reduced somatostatin → increased gastrin and acid → Excess acid reaching the duodenum causes gastric metaplasia, which H. Pylori can then colonise → duodenitis → ulcer → In gastric ulcer: acid is normal or low; the fault lies in impaired defence from pangastritis, atrophy and bile reflux

CLINICAL PEARL

Duodenal ulcer is a disease of too much acid; gastric ulcer is a disease of too little defence. That single distinction explains why duodenal ulcer patients have high or normal acid output while gastric ulcer patients have normal or low output, and why a gastric ulcer — arising in damaged, atrophic, metaplastic mucosa — carries a malignant risk that a duodenal ulcer does not.

Morphology

Usually solitary and under 2 cm; over 4 cm suggests malignancy
Round to oval, "punched out" with sharply demarcated, overhanging margins that are level with the surrounding mucosa — not heaped up
Clean, smooth base owing to peptic digestion of the exudate
Mucosal folds radiate outward from the ulcer like the spokes of a wheel

Layer (from lumen inward)	Contents
1. Necrotic fibrinoid debris	Thin superficial layer of fibrin and cell debris
2. Neutrophil-rich inflammatory zone	Non-specific acute inflammatory infiltrate
3. Granulation tissue	New capillaries, fibroblasts and mononuclear cells
4. Fibrous scar	Dense collagen with obliterative endarteritis of vessels; extends through the muscle wall

Benign Compared with Malignant Gastric Ulcer

Feature	Benign peptic ulcer	Malignant ulcer
Size	Usually under 2 cm	Often over 4 cm
Margins	Sharply "punched out", level with the mucosa	Heaped UP, everted, beaded and irregular
Base	Clean and smooth	Necrotic, shaggy and irregular
Mucosal folds	Radiate right up to the ulcer edge	Stop short, are clubbed or fused
Site	Lesser curvature, antrum	Greater curvature and fundus are more suspicious
Surrounding mucosa	Soft and pliable	Rigid, thickened

Every gastric ulcer must be biopsied — multiple biopsies from the rim and base, and again at follow-up endoscopy to confirm healing. Duodenal ulcers are virtually never malignant and need not be biopsied

Complications

Complication	Details
Haemorrhage — the commonest, 15–20%	Haematemesis and melaena; a posterior duodenal ulcer erodes the gastroduodenal artery and bleeds severely
Perforation — about 5%	An anterior duodenal ulcer perforates into the peritoneal cavity, causing sudden severe pain, board-like rigidity and gas under the diaphragm on an erect radiograph; the commonest cause of death
Penetration	A posterior ulcer penetrates into the pancreas, giving constant back pain
Obstruction	Healing by fibrosis causes pyloric stenosis — projectile vomiting of undigested food, visible peristalsis, a succussion splash, and hypochloraemic hypokalaemic metabolic alkalosis
Malignant transformation	Rare and only in gastric ulcers; more often the lesion was malignant from the start
Hour-glass deformity	Fibrosis of a lesser curve ulcer constricts the stomach

Applied Aspects

Testing for H. Pylori — rapid urease (CLO) test and histology on biopsy; urea breath test and stool antigen non-invasively; serology cannot distinguish current from past infection
Eradication with triple or quadruple therapy heals the ulcer and prevents recurrence — recurrence falls from about 70% a year to under 10%, which transformed the disease from a surgical to a medical one
Proton pump inhibitors with NSAIDs for patients who must continue them, and the lowest effective dose for the shortest time
H. Pylori is very common in India, with seroprevalence around 60–80%, so most carriers never develop an ulcer — testing should be directed, not indiscriminate
Suspect Zollinger–Ellison syndrome with multiple ulcers, ulcers beyond the duodenal bulb, recurrence after eradication, or ulcers with diarrhoea
Endoscopy is mandatory in any patient over 50 with new dyspepsia, or with alarm features — weight loss, anaemia, dysphagia, vomiting or a mass
A bleeding ulcer is treated endoscopically first — injection, clips or thermal coagulation — with surgery reserved for failure; high-dose proton pump inhibitor reduces rebleeding
Perforation requires urgent surgery, and the delay before operation is the strongest determinant of mortality
Elective surgery for peptic ulcer is now rare, having been made almost obsolete by proton pump inhibitors and eradication therapy — a striking example of medical treatment replacing an entire branch of surgery
Confirm eradication with a urea breath test or stool antigen at least four weeks after treatment, since resistance to clarithromycin and metronidazole is rising in India
Proton pump inhibitors must be stopped two weeks before testing, since they suppress the organism and cause false negative urease and breath tests

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