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Acid peptic disease.( Helicobacter pylori. Peptic ulcer )
Incidence-10% of all adult males.
Aetiopathogenesis
Heredity.Strong family history with gastric ulcers, but less strong family history with duodenal ulcers.
Acid-pepsin versus mucosal resistance.
Cause of peptic ulceration is digestion of the mucosa with acid and pepsin of gastric juice. Normal stomach is capable of resisting this digestion. So, the concept of peptic ulceration is acid plus pepsin versus mucosal resistance. Factors which tilt this balance produce ulcers.
Gastric hypersecretion.
Ulcers occur only in the presence of acid and pepsin. Severe ulceration occurs in Zollinger-Ellison syndrome, which is characterised by very high acid secretion. Acid secretion is more important in the aetiology of duodenal ulcer than in gastric ulcer.
Mucosal resistance.
Several mechanisms protect gastric mucosa from the acid.
Surface epithelial cells secrete bicarbonate under the influence of mucosal prostaglandins, and this bicarbonate neutralises the acid.
The surface cells also secrete mucus which impedes the diffusion of ions and molecules such as pepsin. The tight intercellular junctions and the surface lipoprotein layer provide a mechanical barrier.
Normal turnover of epithelial cells has a protective function.
The submucosal area provides adequate micronutrients and oxygen while removing toxic metabolic by¬products of gastric epithelial cells.
Collectively, these mechanisms can be described as the "gastric mucosal barrier".
Prostaglandins play a central role in mucosal resistance. They regulate the release of mucosal bicarbonate and mucus, inhibit parietal cell secretion and are important in maintaining mucosal blood flow. This explains the ulcerogenic properties of non-steroidal anti-inflammatory drugs (NSAIDs).
Factors reducing mucosal resistance.
Several drugs, particularly those used in rheumatoid arthritis.
Aspirin is an important aetiological factor in gastric ulcer. It damages the membrane and tight junctions. It also inhibits prostaglandin synthesis, thus reducing bicarbonate secretion.
Reflux of bile and intestinal contents into stomach due to poorly functioning pyloric sphincter. Other risk factors include smoking and alcohol consumption.
Helicobacter pylori
Majority of gastric and duodenal ulcers can be attributed to NSAIDs and H. pylori.
H. pylori also plays a role in the development of gastritis, MALT (mucosal-associated lymphoid tissue) lymphoma, gastric adenocarcinoma, gastro-oesophageal reflux disease and dyspepsia.
H. pylori is a Gram-negative bacillus which produces mucosal damage.
In a developing country, nearly 80% of persons are colonised with it by the age of 20 years. Other risk factors for acquiring H. pylori infection include poor socioeconomic conditions and family overcrowding.
Transmission occurs following oral-oral or faeco-oral route.
Key factors secreted by the bacillus are urease (which converts urea into ammonia, thus alkalinising the surrounding acidic medium for its survival but simultaneously producing ammonia-induced mucosal damage), catalase, lipase, adhesions, platelet-activating factor and others.
Aetiology of acute and stress ulcers
Aspirin.
Head injury, burns, severe sepsis, surgery and trauma lead to peptic ulceration known as stress ulcers.
Head injury causes ulcers by gastric hypersecretion (Cushing's ulcer).
Burns and shock produce ulcers by reflux of duodenal contents and mucosal ischaemia.
Clinical features
Peptic ulcer is a chronic condition with a natural history of spontaneous relapses and remissions lasting for decades or even life.
The most common presentation is that of recurrent abdominal pain which has three notable characters:
Localisation to the epigastrium.
Relationship to food.
Periodicity.
Epigastric pain.
Pain is referred to epigastrium, and is so sharply localised that the patient will localise the site with one finger (pointing sign). It is usually burning in character.
Hunger pain.
Pain occurs on empty stomach (hunger pain) and is relieved by food or antacids.
Night pain.
Typically, the pain wakes the patient from sleep around 3 A.M. and is relieved by food, milk or antacids.
Pain relief.
Pain is usually relieved by food, milk, antacids, belching or vomiting.
In some patients with gastric ulcer, food may precipitate the pain.
Periodicity (episodic pain).
Pain occurs in episodes, lasting 1-3 weeks every time, three to four times a year. Between episodes, patient is perfectly well.
In the initial stages, the episodes are short in duration and less frequent. As the natural history evolves, the episodes become longer in duration and more frequent.
Patients are more symptomatic during winter and spring.
Relapses are more common in smokers than in non-smokers.
Other symptoms.
Water-brash (excessive salivation), heart burns, loss of appetite and vomiting.
Anorexia, nausea and dyspepsia.
Rarely, the patient might present for the first time with anaemia of chronic blood loss, abrupt haematemesis, acute perforation or gastric outlet obstruction.
Complications
Upper gastrointestinal bleed.
Perforation.
Gastric outlet obstruction (with fluid and electrolyte imbalance).
Gastric malignancy.
Pancreatitis (due to posterior penetration of ulcer).
Investigations
Double contrast barium meal may show the ulcer as a crater or as a deformed duodenal cap.
Endoscopy can visualise the ulcer. A biopsy can be taken from a gastric ulcer to rule out malignancy (10% of gastric ulcers are malignant) and H. pylori infection.
Tests for H. pylori.
Serum gastrin and gastric acid analysis in patients suspected to have Zollinger-Ellison syndrome.
Tests for H. pylori
On endoseopic biopsy material
Rapid urease test (false negative with recent use of proton pump inhibitors, antibiotics).
Histology (sensitivity reduced with use of proton pump inhibitors, antibiotics and bismuth-containing compounds). o Culture (technically demanding).
Non-invasive
Serology for immunoglobulin G (positive results may persist for months after eradication).
Urea breath test (false negative with recent use of proton pump inhibitors, antibiotics).
H. pylori stool antigen test (test for cure 7 days after therapy is accurate; sensitivity reduced with use of proton pump inhibitors, antibiotics and bismuth-containing compounds).
Treatment
Short-term management.
Long-term management.
Intermittent treatment.
Maintenance treatment.
Surgical treatment.
Short-term management
I.General measures
Avoid smoking.
Avoid aspirin and non-steroidal anti-inflammatory drugs. 4 Alcohol to be moderated.
No special dietary advice.
II.Antacids
Mainly prescribed for symptomatic relief only.
Act by neutralising activity.
Minor pain is treated with tablet preparations and severe pain with liquid preparations.
Dose is 15-30 mL liquid antacid 1 and 3 hours after food and at bed time, for 4-6 weeks. 4 Sodium bicarbonate is the quickest acting antacid.
Commonly used antacids are a combination of aluminium and magnesium compounds.
Side effects
Aluminium compounds cause constipation, phosphate depletion and block the absorption of digoxin and tetracycline. 4 Magnesium compounds cause diarrhoea, hypercalcaemia and hypermagnesaemia.
Calcium compounds cause constipation and hypercalcaemia.
Bicarbonate preparations cause alkalosis.
All antacids contain significant sodium, which will lead to water retention, and hence, exacerbation of cardiac failure and ascites.
III.Histamine H2-receptor antagonists
Include cimetidine, ranitidine, famotidine and nizatidine.
All the four are equally effective.
The mechanism of action is inhibition of acid and pepsin secretion by blocking H2-receptors.
Can be prescribed as twice daily doses or as a single large dose at bed time.
Symptomatic relief occurs within days and ulcer healing within weeks.
Duration of treatment of duodenal ulcer patients is 4 weeks. In smokers and in patients who have had recent major complications (haematemesis, perforation), treatment should be prolonged to 6-8 weeks.
Gastric ulcer patients are treated for 6 weeks, followed by endoscopy and further treatment if necessary. A gastric ulcer which has not healed by 12 weeks should be treated with omeprazole or surgery.
Cimetidine - Side effects include gynaecomastia in males, confusion in elderly, oligospen-nia, and delay in elimination of warfarin, phenytoin and theophylline.
Ran itidine -Side effects are confusion and liver dysfunction.
Famotidine - Side effects are headache, dizziness and dry mouth.
Nizatidine - Side effects are sweating, urticaria and somnolence.
IV.Proton pump inhibitors
These are substituted benzimidazoles and include omeprazolc, lansoprazole, pantoprazole, esomeprazole and rabeprazole.
Omeprazole, lansoprazole and esomeprazole should be taken 30 minutes before a meal.
Rabeprazole and pantoprazole may be taken without regard to meals.
Mechanism of action
PPIs cross the parietal cell membrane and enter the acidic parietal cell canaliculus.
In the acidic environment, the PPI becomes protonated, producing the activated form of the drug that binds covalently with the 11+/K+ ATPase enzyme that results in irreversible inhibition of acid secretion by the proton pump.
The parietal cell must then produce new proton pumps or activate resting pumps to resume its acid secretion.
Side effects
The most common side effects are headache, diarrhoea, abdominal pain and nausea.
Efficacy in peptic ulcer disease
PPIs have superior healing rates, shorter healing time and faster symptom relief compared to H2-blockers.
All PPIs appear to have similar efficacy in the treatment of various acid-peptic disorders.
Dosage
Omeprazole: 20 mg daily for 4-8 weeks.
Lansoprazole: 15-30 mg daily for 4-8 weeks. Esomeprazole: 20-40 mg daily for 4-8 weeks. Pantoprazole: 40 mg daily for 4-8 weeks.
Rabeprazole: 20 mg daily for 4-8 weeks.
Indications
Reflux oesophagitis and GERD.
Peptic ulcer unresponsive to other medical measures. As an adjunct to anti-H, pylori treatment.
Zollinger-Ellison syndrome.
V. Prostaglandin analogues
Misoprostol four times daily. Useful in preventing NSAID-induced mucosal injury.
It inhibits acid secretion and stimulates bicarbonate and mucus secretion. Side effects are diarrhoea and abortefacient activity.
VI.Colloidal bismuth compounds
Bismuth subsalicylate and colloidal bismuth subcitrate.
Mechanisms of action are two:
I. These precipitate in acid conditions, binding with proteins in the ulcer base to form a coat which protects against further acid-pepsin digestion.
2. Powerful antimicrobial effect against Helicobacter pylori.
Side effects include blackening of tongue, teeth and face, and bismuth toxicity (neurotoxicity).
VII.Sucralphate
Dose is 2 g BD.
Forms a protective coating for the ulcers.
Side effects are reduction in the absorption of warfarin, phenytoin, tetracycline and digoxin.
VIII.Carbenoxolone sodium
Side effects include sodium retention, hypokalaemia and hypertension. Not used presently.
IX. Treatment for H. pylori
Many clinicians administer drugs against H. pylon to all patients with peptic ulcer disease even without documenting the presence of bacteria.
It reduces the risk of recurrence of ulcer formation.
Triple or quadruple therapy is recommended.
Treatment of H. pylori infection
Omeprazole (20 mg BID)' + Clarithromycin (500 mg BID) + Metronidazole (500 mg BID) for 14 days.
Omeprazole (20 mg BID) 11+ Clarithromycin (500 mg BID) + Amoxicillin (1 g BID) for 14 days.
Orneprazole (20 mg OD)# + Bismuth subsalicylate (525 mg QID) + Metronidazole (250 mg QID) + Tetracycline (500 mg QID) for
14 days.
Lansoprazole (30 mg BID) may be substituted for omeprazole.
Long-term management
Intermittent treatment
For symptomatic relapses less than four times a year. 4 4 weeks course of one of the ulcer healing agents.
Maintenance treatment
1.Symptomatic relapses more than four times per year.
2.History of life-threatening complications like repeated bleeding or perforation.
3.When the risk of future complications is low, operation must be avoided.
Long-term maintenance is with H2-receptor antagonists (cimetidine 400 mg at night, ranitidine 150 mg at night, famotidine 20 mg at night or nizatidine 150 mg at night).
Surgical treatment
For gastric ulcer, the procedure of choice is partial gastrectomy with a Billroth I anastomosis. 4 Duodenal ulcer treatment could be:
Truncal vagotomy plus pyloroplasty or gastroenterostomy.
Selective vagotomy with pyloroplasty.
Highly selective vagotorny.
Dumping syndrome.
Dumping syndrome follows surgery for peptic ulcer disease.
It usually occurs after a sweet food.
Two phases of dumping may occur: early and late dumping.
Early dumping syndrome occurs 15-30 minutes after meals and consists of crampy abdominal pain, nausea, diarrhoea, sweating, tachycardia, palpitations, light-headedness and occasionally syncope. It arises due to rapid emptying of hyperosmolar gastric contents into the small intestine, resulting in fluid shift from blood into the lumen of the gut. This causes intravascular volume contraction and intestinal distension.
Late dumping occurs 2-3 hours after meals. The patient gets sweating, light-headedness, palpitations, tachycardia
and occasionally syncope. It is possibly related to excessive insulin secretion causing hypoglycaemia.
Treatment—patient should be asked to avoid simple carbohydrate food and also to take meals in small amounts at
frequent intervals. Some patients require an anticholinergic agent. Octreotide given subcutaneously before the meal
may be used in refractory cases.
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