The defensive forces – Bicarbonate –Mucus layer – Mucosal blood flow –Prostaglandins –Growth factors The aggressive forces –Helicobacter pylori –HCl acid –Pepsins –NSAIDs –Bile acids –Ischemia and hypoxia. –Smoking and alcohol When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions and ulcerations. Gastric Mucosa & Secretions
Structural Considerations Mechanisms that maintain mucosal integrity
The two most common causes of PUD are: –Helicobacter pylori infection –Non-steroidal anti-inflammatory drugs (NSAIDS) Other uncommon causes include: –Gastrinoma (Gastrin secreting tumor) –Stress ulceration (trauma, burns, critical illness) –Viral infections –Vascular insufficiency Etiology
Helicobacter pylori as a cause of PUD The majority of PUD patients are H. pylori infected. Studies show that about 95% of patients with DU and 85% with GU are infected with H. pylori Cure of H. pylori infection reduces ulcer recurrence. Etiology – Helicobacter pylori
Helicobacter pylori as a cause of PUD Over a 10 year period 1 out of 133 (0.75%) individuals without H. pylori developed a peptic ulcer, compared with 35 out of 321 (11%) with H. pylori infection. The incidence of peptic ulcers in H.pylori infected people is about 1% per year. Etiology – Helicobacter pylori
Non-steroidal anti-inflammatory drugs (NSAIDs) Symptomatic GI ulceration occurs in 2% to 4% of patients treated with NSAIDs for 1 year. In view of the million of people who take NSAIDs annually, these small percentages translate into a large number of symptomatic ulcers. The effects of aspirin and NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions and acute ulcers. Etiology – NSAIDs
Etiology – NSAIDS Effect of NSAIDS All NSAIDs reduce the mucosal production of prostaglandins from precursor membrane fatty acids. The drugs also generate oxygen-free radicals and products of the lipoxygenase pathway that may contribute to ulceration.
Etiology – NSAIDS Users of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events than nonusers. Additional risk factors include: –Age greater than 60 years –Smoking –Previous history of GI events –Concomitant corticosteroid use. In terms of serious complications, the combination of steroids and NSAIDs leads to a 10-fold increase in GI bleeding and a 20-fold increase in GI-related death.
Etiology – NSAIDS Type of NSAID and Risk of Ulcer Risk GroupDrugRelative Risk LowIbuprofen 2.0 Diclofenac 4.2 MediumNaproxen 9.1 Indomethacin11.3 Piroxicam13.7 HighKetoprofen23.7 Azapropazone31.5
Tests for Helicobacter pylori Non-invasive C 13 or C 14 Urea Breath Test Stool antigen test H. pylori IgG titer (serology) Invasive Gastric mucosal biopsy Rapid Urease test Diagnosis of H. pylori
3. Protect mucosa from damage Agents that coat the mucosa and protect from acid irritation - Bismuth subcitrate (colloidal suspension) - Sucralfate (complex of aluminium hydroxide and sucrose) Peptic Ulcer+ sucralfate After 5 days of treatment
4. Eradicate causative agent (H. pylori) Most common cause of gastric ulcers. Infects ~ 30% population. Readily detected with ‘urea breath test’, blood test (for antibodies). H. Pylori invades the stomach and duodenal lining, weakens the resistance of the lining to acid and stimulates acid secretion. Local inflammation can also be observed.
Treatment of NSAID-induced gastric ulcers 1. Stop NSAID, if possible. 2. If NSAID required, use lowest effective dose, for shortest period. 3. Effective treatment with proton pump inhibitor (Pantoprazole). Guide to minimising NSAID gastric ulcer risk: Low vascular Risk High vascular Risk Low NSAID riskHigh NSAID risk Non-selective NSAID COX2-selective NSAID or Non-selective NSAID + PPI Non-selective NSAID with/without PPI Non-selective NSAID + PPI [Always check for H. pylori involvement]
Regimen for eradication of H pylori: TRIPLE THERAPY X 14 DAYS: [PPI + Clarithromycin 500 mg + ( Metronidazole 500 mg or amoxicillin 1 g)] twice a day. (Tetracycline 500 mg can be substituted for amoxicillin or metronidazole.) QUADRUPLE THERAPY x 14 DAYS: PPI twice daily + Metronidazole 500 mg three times daily + (Bismuth subsalicylate 525 mg + tetracycline 500 mg four times daily) OR H2 receptor antagonist twice a day + ( Bismuth subsalicylate 525 mg + Metronidazole 250 mg + tetracyclione 500 mg) four times daily