Git 8th Pud Davidson.
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Peptic ulcer disease is caused by an imbalance between aggressive factors like acid and pepsin and defensive mucosal factors. Helicobacter pylori infection is the most important cause, causing chronic gastritis. Smoking, NSAIDs, and genetic factors also increase risk. H. pylori eradication is the cornerstone of treatment and prevents recurrence in most cases. Symptoms include recurrent abdominal pain relieved by food or antacids. Endoscopy is required for diagnosis and management involves eradication of H. pylori along with acid suppression medications.
Git 8th Pud Davidson.
- 1. Peptic Ulcer Disease( PUD): Dr.Mohammad Shaikhani.
- 2. Introduction: Discontinuation of the mucous membrane of the GIT. Acute or chronic; both penetrate the muscularis mucosae but in acute ulcer no evidence of fibrosis. Erosions do not penetrate the muscularis mucosae. Locations: duodenum, stomach, lower oesophagus, or in the jejunum after Gastrojejunostomy or, rarely, in the ileum adjacent to a Meckel's diverticulum.
- 3. GASTRIC & DUODENAL ULCER : The prevalence is decreasing in Western communities as a result of widespread H. pylori eradication, but high in developing countries. Male/female for DU 5:1-2:1, for GU is 2:1 or less.
- 4. Aetiology: H Pylori. NSAIDs. Smoking. Genetics.
- 5. Aetiology: H pylori The most important cause. HP prevalence rises with age, 50% > 50 years are infected. In developing world HP is much more common, usually acquired in childhood & up to 90% of the adults are infected. The vast majority of colonised people remain healthy/ asymptomatic& only a minority develop clinical disease. 90% DU, 70% GU are infected with H. pylori ; the remaining 30% GU are due to NSAIDs.
- 6. H pylori: Pathophysio H. pylori is Gram-negative, spiral with multiple flagella at one end which make it motile, allowing it to burrow& live deep beneath the mucus layer closely adherent to the epithelial surface. It uses an adhesin molecule (BabA) to bind to the Lewis b antigen on epithelial cells,where the surface pH is close to neutral & any acidity is buffered by the organism's production of the enzyme urease.produces ammonia from urea, raises the pH around the bacterium & between its two cell membrane layers. The bacteria spread by person-to-person contact via gastric refluxate or vomitus. H. pylori exclusively colonises gastric-type epithelium& found in the duodenum only in association if there are patches of gastric metaplasia.
- 7. H pylori: Pathophysio Causes chronic gastritis by provoking a local inflammatory response in the underlying epithelium, depends on numerous factors; bacterial factors as expresion of cagA / vacA genes & host factors.
- 8. H pylori: Pathophysio Bacterial factots: H. pylori strains expressing cagA (cagA+) are more often associated with disease than cagA- strains. Most strains also secrete a large pore-forming protein called vacA causes large vacuoles to form in cells in vitro.
- 9. H pylori: Pathophysio Host factors: Genetic polymorphisms; for example, greater levels of expression of the proinflammatory cytokine interleukin-1β (IL-1β) are associated with greater risk of gastric atrophy & subsequent carcinoma &polymorphisms in other genes involved in the host inflammatory response to infection (e.g. IL-10 / TNF-α) may also be important.
- 10. H pylori: Pathophysio In most people H. pylori causes antral gastritis associated with depletion of somatostatin (from D cells)& gastrin release from G cells unchecked by somatostatin. The subsequent hypergastrinaemia stimulates acid production by parietal cells, but in the majority of cases this has no clinical consequences. In a minority of patients (perhaps smokers) this effect is exaggerated, leading to duodenal ulceration The role of H. pylori in the pathogenesis of gastric ulcer is less clear but probably acts by reducing gastric mucosal resistance to attack from acid/pepsin. In 1% of infected people, H. pylori causes a pangastritis leading to gastric atrophy/ hypochlorhydria,allows bacteria to proliferate within the stomach; these may produce mutagenic nitrites from dietary nitrates, predisposing to the development of gastric cancer
- 13. Factors which influence the virulence of H. pylori .
- 14. HP Diagnosis: Urea Breath tests are best because of their accuracy, simplicity & non-invasiveness.
- 15. HP Diagnosis: Others Lacks sensitivity Defines antibiotic sensitivity Slow / laborious 'Gold standard' Microbiological culture Lack sensitivity Cheap, quick Specificity Rapid urease tests, e.g. CLO, Pyloritek Takes several days to process False negatives occur Sensitivity and specificity Histology INVASIVE (ANTRAL BIOPSY) Acceptability Cheap, accurate Faecal antigen test 13 C requires expensive mass spectrometer 14 C uses radioactivity High sensitivity and specificity Urea breath tests Cannot differentiate current from past infection Good for population studies Lacks sensitivity and specificity Rapid office kits available Serology NON-INVASIVE Disadvantages Advantages Test
- 16. Smoking: Smoking confers an increased risk of gastric ulcer & to a lesser extent, duodenal ulcer. Once the ulcer has formed, it is more likely to cause complications& less likely to heal if the patient continues to smoke. NSAIDs
- 17. Acid-pepsin vs mucosal resistance: Ulcer forms when there is imbalance between aggressive factors, i.e. acid /pepsin & defensive factors, i.e. gastric /duodenal mucosa, bicarbonte, mucosal blood flow* PGs. Ulcers occur only in the presence of acid /pepsin; never found in achlorhydric as pernicious anaemia& severe intractable PU nearly always occurs in ZES, characterised by very high acid secretion. Most DU have markedly exaggerated acid secretion in response to stimulation by gastrin& H. pylori leads to hypergastrinaemia. In GU the effects of H. pylori are more complex&impaired mucosal defence resulting from a combination of HP, NSAIDs&smoking have a more important role.
- 18. Gastroduodenal mucosal protection; PG stimulate HCO3 /mucus secretion& increase mucosal blood flow.
- 19. Clinical features: Chronic with spontaneous relapse /remission lasting for decades, if not for life. DU/GU share common symptoms. Recurrent abd pain with 3 notable characteristics: epigastric , episodic & relationship to food . Occasional vomiting occurs in 40%; persistent daily vomiting suggests GOO. In 1/3 history is less characteristic, esp in elderly on NSAIDs, pain may be absent or slight epigastric unease. Occasionally, only anorexia / nausea, or a sense of undue repletion after meals. In some completely 'silent', presenting for the first time with anaemia, abrupt haematemesis or as acute perforation; recurrent acute bleeding. The diagnostic value of individual symptoms is poor.
- 20. Diagnosis: Endoscopy is the preferred investigation. Gastric ulcers may occasionally be malignant& therefore must always be biopsied & followed up to ensure healing
- 21. Management: Aims: relieve symptoms, induce healing ,prevent recurrence. H. pylori eradication is the cornerstone of therapy, as this will successfully prevent relapse& eliminate the need for long-term therapy in the majority. H. pylori eradication All patients with proven acute or chronic DU &GU who are H. pylori-positive should be offered eradication as primary therapy. Treatment is PPI simultaneously with two antibiotics (from amoxicillin, clarithromycin , metronidazole) for 7 days. Success is > 90%, although compliance, side-effects& metronidazole resistance influence the success of therapy. Second-line therapy should be offered to those patients who remain infected after initial therapy,choice lies between a third attempt with quadruple therapy (bismuth, PPI+ 2 antibiotics) or long-term maintenance therapy with PPI.
- 22. Management: H. pylori / NSAIDs are independent risk factors for ulcer High risk patients requiring long-term NSAIDs should first undergo eradication therapy to reduce ulcer risk. This may not be necessary in young, fit patients with no history of ulcer disease or dyspepsia but a 'test & treat' strategy for older patients with major comorbidity or a previous ulcer history is recommended. Subsequent co-prescription of PPI+ NSAID is advised but is not always necessary for patients being given low-dose aspirin in whom the risk of ulcer complications is lower
- 23. COMMON SIDE-EFFECTS OF HP ERADICATION: Diarrhoea 30-50%; usually mild but Clostridium difficile-associated colitis can occur. Flushing & vomiting when taken with alcohol (metronizadole) Nausea, vomiting Abdominal cramp Headache Rash
- 24. Other indications OF HP ERADICATION: Definite Peptic ulcer MALToma H. pylori-positive dyspepsia Not indicated Asymptomatic Gastro-oesophageal reflux disease Uncertain Family history of gastric cancer Non-ulcer dyspepsia Low risk Long-term NSAID users
- 25. General measures: Cigarette smoking, aspirin/ NSAIDs should be avoided. Alcohol in moderation is not harmful. No special dietary advice is required. Short-term management: many different drugs are available for of acid peptic symptoms. Maintenance treatment: Continuous maintenance treatment should not be necessary after successful H. pylori eradication. For the minority who do require it, the lowest effective dose should be used.
- 26. Diarrhoea; abortifacient-contraindicated in women of child-bearing age Enhance mucosal blood flow, stimulate mucus and bicarbonate secretion; stimulate epithelial proliferation Misoprostol PGs Caution in renal impairment; reports of bezoar formation Aluminium salt of sucrose octasulphate; little effect on acid -may protect ulcer base from peptic activity and enhance epithelial cell turnover Sucralfate C,Salts May darken tongue and stools Ammoniacal suspension of complex bismuth salt; anti- H. pylori activity and enhances mucosal protection Tripotassium dicitratobismuthate Chelat Potent acid suppression and rapid ulcer healing; used in H. pylori therapy; superior to H 2 antagonists for healing ulcers and oesophagitis Irreversible inhibitors of H + /K + ATPase on parietal cell surface Omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole PPI Less potent than PPIs; good safety profile- some available without prescription; cimetidine may interfere with warfarin and phenytoin metabolism via cytochrome P450 Competitive inhibitors of H 2 -receptors on parietal and ECL cells Ranitidine, cimetidine, famotidine, nizatidine H 2 -Bs Aluminium salts block digoxin absorption and are constipating while magnesium salts can cause diarrhoea; some have high sodium content and can exacerbate cardiac failure Antacids; alginates form protective mucosal 'raft' Aluminium hydroxide, magnesium trisilicate, alginic acid antacid Comments Mechanism Examples Group
- 27. Proglumide ACh PGE 2 Histamine Gastrin Adenyl cyclase ATP cAMP Protein Kinase (Activated) Ca ++ Ca ++ Proton pump K K + H + Gastric acid Parietal cell Lumen of stomach H 2 M 3 PGE receptor Gastrin receptor _ + + Antacid Omeprazole Ranitidine Misoprostol _ _ _ _ + + + + + +
- 28. Surgery: The cure of most peptic ulcers by H. pylori eradication & availability of safe, potent acid-suppressing drugs have made elective surgery for PUD a rare event
- 29. Complications: Perforation Ggastric outlet obstruction Bleeding
- 30. PEPTIC ULCER DISEASE IN OLD AGE: Gastroduodenal ulcers: have a greater incidence, admission rate & mortality. Causes: high prevalence of H. pylori & NSAID use& impaired defence mechanisms. Atypical presentations: pain &dyspepsia are frequently absent or atypical so older people develop complications such as bleeding or perforation more frequently. Bleeding: older patients require more intensive management (including central venous pressure measurement) than younger patients because they tolerate hypovolaemic shock poorly.