Peptic Ulcer Disease

By: Dr. Abhimanyu Prashar

PUD: “A condition in which there is a discontinuity in the entire thickness of the gastric or duodenal mucosa”

Ulcers:

“The areas of degeneration and necrosis of gastrointestinal mucosa exposed to acid and pepsin

secretion”

Regulation of gastric acid secretion

Mediated by 3 pathways: Neurocrine (Ach)Paracrine (Histamine)Endocrine (Gastrin)

• Activation of proton pump exchange of H+

• In addition, histamine, gastrin & ach receptors stimulate H+ production

• Ach from post ganglionic vagal neurons• Gastrin fron antral G cells stimulates pepsinogen secrection,

hepatic bile flow & pancreas (insulin)

It also stimulates gastric & intestinal motility

Directly stimulates Hcl secretion by acting on gastrin receptors on parietal cells

Gastrin activates ECL cells which releases histamine

Histamine activates H2 rec, results in activation adenylate cyclase which convers ATP to cAMP and subsequent generation of H+ & proton pump mobilses & activated

Autoregulatory mechanism: Ingestion of meal gastrin release gastric acid

secretion decreased PH release of somatostatin from D cells decreased release of gastrin, inhibits acid secretion, suppress histamine release

Other NTs, vasoactive intestinal peptide, galanine, serotonin, are also involved in direct or indirect regulation of gastric acid secretion

Epidemiology PUD is more common in unskilled labourers and low socioeconomic

groups

Smokers and individuals who are on NSAIDs are more prone to develop PUD

About 10% of the population in developed countries likely to be affected by PUD

Duodenal ulcer is 4 times more common than gastric ulcer

Etiopathogenesis

Infection with Helicobacter pylori

Use of NSAIDs

Local irritants

Dietary factors

Hormonal factors

Decreased mucous secretion

H.pyloriA spiral gram negative bacterium

95% of duodenal ulcers & 85% of gastric ulcers are associated with H.pylori infection

H.Pylori produces Cag A proteins and vacuolating cytotoxins (Vac A) which activates inflammatory cascade

It expresses sialic acid specific haemagglutinins and a lipid binding adhesion that mediate binding to the mucosal surface

Enzymes like urease, haemolysins, neuraminidase and fucosidase involve in tissue damage

Altered gastrin homeostasis in H.pylori infection

Hypergastinaemia leads to inflammation and ulcer formation

Use of NSAIDs

NSAIDs cause 3 patterns of mucosal damage Superficial erosions & haemorrhagesSilent ulcers detected at endoscopyUlcers causing clinical symptoms

Mechanism: reduction of mucosal PGs production

Approx. 20% of patients taking NSAIDs experience Dyspepsia

Approx. 4% of NSAID users suffer from ulcer and ulcer complications

Local irritants

Pyloric antrum & lesser curvature of stomach most exposed

for longer periods of irritants (like spicy food, alcohol,

tobacco smoking) hence these are common sites for

occurrence of gastric ulcer

Dietary factors

Poor socio-economic status (malnutrition)

Irregular food habits

Social habits

Consumption of spicy food

Hormonal factors

Zollinger-Ellison syndrome (acid secreting tumours) leads to massive hypersecretion of gastric acid

Decreased mucous secretion

Conditions like stress, anxiety that decreases quantity

or quality of normal protective mucous barrier predisposes

to the development of PUD

Clinical features

Duodenal ulcer

• Pain-food relief pattern• Night pain common• No vomiting• Melena (blood in stool)

more common• No loss of weight

Gastric ulcer

• Food-pain pattern• No night pain• Vomiting present• Hematemesis (blood in

vomit) more common• Significant loss of weight

Investigations

Endoscopy

Radiology

H. pylori detection:

Serology to detect Abs

Urea breath test

Histology & culture

Management

Triple therapy

Omeprazole 20 mg PO bid+

Clarithromycin 500 mg PO bid for 7 days+

Amoxicillin 1 gram PO bid

Omeprazole 20 mg PO bid+

Clarithromycin 500 mg PO bid for 7 days

+Metronidazole 400 mg PO tid

Quadruple therapy

Bismuth 107.7 mg PO qid+

Metronidazole 200 mg PO tid & 400 mg at night

+Tetracycline 500 mg PO qid

for 14 days+

Omeprazole 20 mg or Lansoprazole 30 mg or Pantoprazole 40 mg PO bid

Follow on antisecretory therapy for complicated ulcers and larger ulcers of ≥ 1 cm

diameter H2 Rec antagonists

Ranitidine 300 mg POor

Nizatidine 300 mg POor

Famotidine 40 mg POor

Cimetidine 800 mg PO

With evening meal For additional 4-6 weeks

PPIs

Pantoprazole 40 mg PO or

Lansoprazole 30 mg PO or

Omeprazole 20 mg PO or

Rabeprazole 20 mg PO

For additional 2-4 weeks

Bleeding peptic ulcers

Endoscopic haemostasis using a heater probeor

Inj. Adrenaline 1: 10000 or 1: 100000

Omeprazole 80 mg as a bolus dose then 8 mg/hr infusion for 3 days

Stress ulceration prophylaxis

Ranitidine 300 mg PO 1-0-1or

Famotidine 40 mg PO 1-0-1or

Sucralfate 1 gram every 6 hourlyor

Omeprazole 20/40 mg PO 1-0-1or

Pantoprazole 20/40 mg PO 1-0-1

Antacids

Magnesium hydroxide (1g≈ 30 m eq HCl)

Magnesium trisilicate (1g ≈ 10 m eq HCl)

Aluminium hydroxide gel (5 ml ≈ 1 m eq HCl)

Calcium carbonate (1g ≈ 20 m eq HCl)

Sodium bicarbonate (1 g ≈ 12 m eq HCl)

Sodium citrate (1g ≈ 12 m eq HCl)

Ulcer protective drugs

Sucralfate (aluminium salt of sulphated sucrose)

Colloidal bismuth sub citrate

Prostaglandin analogues:

Misoprostol (methyl PGE1 ester) 200 mcg

Anticholinergics:

Pirenzepine 100-150 mg/day

Drugs causing dyspepsiaCorticosteroidsBisphosphonates Potassium chlorideIronAntibioticsCCBsNitratesTheophyllineDrugs with anti muscarinic effects e.g. TCAsNSAIDs:

High risk: Long acting - piroxicam, ketoprofenlow risk: short acting- ibuprofen, diclofenacreduced risk: highly selective COX-2 inhibitors

ZES

Characterized by severe peptic ulceration,

gastric acid hyper secretion and a non β-cell

islet tumor of the pancreas (gastrinoma)

ZES is the cause of about 0.1 % of cases of duodenal ulceration

Gastrinoma

Large amount of gastrin

Parietal cells

Maximal acid secretion & increased parietal cell mass

Increased acid output

Reduced luminal PH to 2 or less

Inactivate pancreatic lipase & precipitates bile acids

Diarrhea & steatorrhoea

Secretes

Stimulates

Path

ogen

esis

Clinical features:Diarhoea & Steatorrhoea

Investigations:serum gastrin levelsEndoscopic ultrasound

Management

Non-pharmacological:Tumor resection

Pharmacological:Omeprazole 60-80 mg/D

Synthetic somatostatin analogue:Octreotide SC 200-300 mcg/D

BD