PEPTIC ULCER DISEASE DEFINITION: A disease characterized pathologically by ulceration of the mucosa of stomach, duodenum and some time of the lower oesophagus or in a mickle diverticulum. It results when aggressive factors overwhelm defensive factors involved in mucosal resistance. It is characterized clinically by epigastric pain and dyspepsia with remission and relapses.

Etiology & pathophysiology Still the precise mechanism of PUD is unclear, but we know that PUD results when aggressive factors overwhelm defence factors ( mucosal injury-protection balance). Injurious factors : Endogenous Acid, pepsin, bile acids and small intestine contents. Exogenous Ethanol, Aspirin, NSAIDs, and Helicobacter pylori. Protective factors: Mucus, bicarbonate, mucosal blood flow, prostaglandins, and EGF.

Etiology & pathophysiology 1- Helicobacter pylori associated PUD : PUD is strongly associated with H.pylori infection It is a slow-growing gram negative spiral, with multiple flagella make it motile and allowing it to burrow and live deep beneath the mucus layer closely adherent to the epithelial surface. It is protected from gastric acid by the juxta-mucosal mucous layer which trap bicarbonate secreted by antral cells, and ammonia produced by bacterial urease. The mechanism by which HP are involved in pathogenesis of peptic ulcer are unclear, but HP produce ammonia and other toxines that may directly damage the mucosa and initiate an inflammatory response. It causally associated with DU because inpatient with DU: A- 95% are infected with HP in the antrum. B- Cure of infection heals ulcer and stop ulcer recurrence.

The Nobel Prize in Physiology or Medicine 2005 "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease" Barry J. Marshall Australia J. Robin Warren Australia b b. 1951

Etiology & pathophysiology 2- NSAIDs related PUD : Aspirin and NSAIDs causes mucosal injury and ulceration of oesophagus, stomach and duodenum by both direct mucosal injury and inhibition of prostaglandins that are protective to the mucosa. Increasing risk for mucosal damage by: A. History of PUD. B. High dose of NSAID. C. Concomitant steroid use. D. Use of more than one NSAID. E. Presence of HP infection.

3- Acid related PUD : Acid appears to be essential for benign peptic injury to occur. A PH of 1 to 2 maximizes the activity of pepsin. Furthermore, mucosal injury from aspirin, NSAIDs, & bile acids is augmented in the presence of acid. Etiology & pathophysiology

4- Others : A- Genetic susceptibility B- Hypersecretory syndromes Etiology & pathophysiology

5- Smoking : A. Smokers are more likely to have PUD. B. Difficult to heal, longer period of treatment higher dose of drugs, and refractory. C. Relapses more and sooner D. Stop smoking, recurrence as nonsmoker. Etiology & pathophysiology

PUD is a chronic condition with a natural history of spontaneous relapse and remission lasting for decades. Gus and DUs share common symptoms which are: 1. Abdominal pain - Recurrent - Epigastric - Relation to food 2. Vomiting 3. Anorexia and nausea 4. Silent - Anaemia, Haematemesis or perforation. CLINICAL FEATURE

1.History and Physical examination. 2.Diagnostic studies: A.Patients under 55 years of age, typical symptoms & HP positive, start eradication therapy. Diagnosis of HP infection: Noninvasive : 1. Serology sensitive but less specific. Not useful for eradication. 2. Urea breath test high sensitivity 97% and specificity 96%. Very suitable for testing for eradication. 3. Stool antigen test highly sensitive 98% and specific 96%. Very suitable for diagnosis & monitoring efficacy of eradication. Invasive (endoscopy): 1.Biopsy urease test 2.Histology. 3.Culture B. Patients above 55 years of age, Upper GI Endoscopy & biopsy : DIAGNOSIS

Upper GI Endoscopy & biopsy The gold standard for the diagnosis of HP infection, beacuase histology not only confirms the presence of HP,but also gives information on the presence or absence of gastritis, gastric atrophy, intestinal metaplasia, MALT lymphoma, and cancer. Sensetivity & Specificity 95%. False negative result in: a.Recent GI bleed. b.Use of bismuth c. Use of antibiotics. d.Use of sucralfate. e.Use of acid –suppressive therapy. Accordingly endoscopy is indicated for: 1.Patients above age of 55 years with dyspepsia. 2.Patients with GU. 3.Patients with dyspepsia and alarm symptoms. DIAGNOSIS

1. GERD 2. GB disease 3. Pancreatic disease 4. Cancer of stomach, pancreas, and billiary system. 5. Mesenteric vascular insufficiency 6. Irritable bowel syndrome (IBS) DIFFERENTIAL DIAGNOSIS

1. Diet: A. Food - no rigid restriction on diet. - small frequent feeding are unnecessary. B.Drugs and life-stile modification. - Stop smoking - Stop aspirin and NSAIDs. - Restriction of alcohol and coffee. 2. Drug therapy: TREATMENT

A. HP associated PUD : Current recommendations are that all patients with duodenal and gastric ulcers should have HP eradication therapy. Standard eradication therapies are successful in 90%. Regimens used are: 1.First-line eradication therapy PPI 12 –hourly + Amoxil 1gm + Clarithromycin 500 mg 12-hourly for 7 days. 2.Second-line eradication therapy: PPI + Bismuth subsalicylate + Metronidazole +Tetracycline TREATMENT

Side-effects of HP Eradication therapy 1. Diarrhoea 30-50%. 2. Nausea and vomiting. 3. Abdominal cramps. 4. Headache. 5. Rash. 6. Flushing and vomiting ( metronidazole & alcoh).

B. NSAIDs – Related PUD: 1. Stop offending drug and start anti-secretory. 2. Give PPI or Prostaglandin E derivative if unable to stop NSAIDs. TREATMENT

C. Acid-related PUD : Here we have a group of patients who are HP negative and not on NSAIDs. The treatment here is to releave symptoms by controlling acid secretion. We have a wide variety of anti-secretory drugs. There is little difference in efficacy among Antacid, H2 antagonist, Prostaglandin, and Scrulfate. However proton-pump inhibitor offers advantages in : 1. Acceleration of healing (2weeks) 2. Remarkably safe. TREATMENT

H2 antagonists : They block histamine receptors on parietal cells and are potent inhibitor s of acid secretion. We have four drugs. 1. Cimetidine ( Tagamet) 200 mg X Ranitidine ( Zantac ) 150 mg X Famotidine( pepcid ) 20 mg X Nizatidine ( Axid ) 300 mg Noct. Side effects are : 1. Leukopenia 2. Skin rash 3. Elevated Liver enzymes 4. Constipation 5. Gynaecomastia. TREATMENT

Prostaglandins : Are attractive on theoretical grounds because they affect both sides of the mucosal injury –protection balance. They inhibit acid secretion and exert a cytoprotective effect on the mucosa. Prostaglandin analogs, misoprostol ( Cytotec ) 2oo mg X 4 / day is as effective as H2 antagonist. Side effects : 1. Diarrhoea 2. Abdominal cramping pain 3. Abortion in pregnant women. TREATMENT

Proton-pump inhibitors (PPIs) : They inhibit gastric acid secretion nearly completely by covalently binding to the H+ - K+ - ATPase (Proton pump) in the luminal aspect of the cell membrane of parietal cells. There are five drugs: 1. Omeprazole 20 mg X 2 /day. 2. Lansoprazole 30 mg X 2 /day. 3. Rabeprazole 20 mg X 2 /day. 4. Pantoprazole 40 mg X 2 /day. 5. Esomprazole 40 mg X 2 /day. Because PPIs are safe, have minimal side effects, and heals peptic ulcers faster than H2-blockers ( 2ws v 4ws) they are the drugs of first choice in the treatment of peptic ulcer disease. TREATMENT

Treatment of hypersecretory Syndromes : 1.Gastrinoma (ZES) : - PPIs in high dose mg - Highly selective vagotomy. 2.Antral G-cell hyperplasia : - PPIs in high dose - +/- anterectomy 3.Retained antrum syndrome : - Reoperation to remove the retained antrum. - Omeprazole in high dose. TREATMENT

1.Bleeding 2.Perforation 3.Obstruction 4.Penetration Complications of peptic ulcer disease

Surgery for PUD has decreased because of effective medical treatment and decline in prevalance of peptic ulcer disease. However surgery is needed for complications. Procedures done are: 1. Truncal vagotomy and pyloroplasty. 2. Highly selective vagotomy ( Proximal gastric vagotomy) 3. Billruth l and Billruth ll. Surgical treatment of PUD