1. Peptic Ulcer
Dr. Basil Al Dileamy

2. Ulcer: is disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation.
DUs: occur in D1 in more than 95% with about 90% located within 3 cm of pylorus. They are usually equal or less than 1 cm in diameter , occasionally reach 3-6 cm (giant ulcer).
GUs: Can represent a malignancy in contrast to DUs. The benign GU often found distal to the junction between the antrum and the acid secretory mucosa. 2

3. Pathophysiology
DU: H. Pylori and NSAID induced injury account for the majority of DUs.
GUs: As in DUs the majority of Gus can be attributed to either H. Pylori or NSAID induced mucosal damage.
H. Pylori and acid peptic disorders: gastric infection with the bacterium H. Pylori accounts for the majority of PUD.
Pathophysiology:
The particular end result of H.pylori infection ( gastritis, PUD, gastric MALT lymphoma, gastric cancer) is determined by a complex interplay between bacterial and host factors
1- Bacterial factors: H.pylori is able to facilitate gastric residence, induce mucosal injury and avoid host defense. A specific region of the bacterial genome, the pathogenicity island, encodes the virulence factors Cag A and pic B. Vac A also contributes to pathogenicity, though it not encoded within the pathogenicity island.
Urease allow the bacteria to reside in the acidic stomach, generate NH3 which can damage epithelial cells. H. pylori makes proteases and phospholipases that break down the glycoprotein lipid complex of the mucous gel, thus reducing the efficacy of this first line of mucosal defense.
2- Host factors: the inflammatory response to H . Pylori includes recruitment of neutrophils, lymphocytes (T and B) , macrophages, and plasma cells. The pathogen leads to local injury leading to cell death (apoptosis) moreover bacterial strains that encode cag-PAI can introduce Cag A into host cells, leading to further cell injury and activation of cellular pathways involved in cytokine production

4. Clinical features ◑ History:
Abdominal pain: - is common GI disorders including DU and GU but poor predictive value for presence of either Du or Gu.
Up to 10% of patients with NSAID induced mucosal disease can present with complications ( bleeding or perforation and obstruction).
Epigastric pain occur as burning or gnawing discomfort can be present in both GU and DU.
The typical pain pattern in DU occurs min to 3 h after a meal and frequently relieved by food or antacids.
Pain that awakes the patent from sleep (between midnight and 3 A.M.) is the most discriminating symptom with 2 thirds of DU patients describing this complint.
The pain pattern in GU patients may be different from that in DU patients where discomfort may actually be precipitated by food.
Nausea and weight loss occur more commonly in GU patients. .
Vomiting: is infrequent but often relieve pain, while persistent daily vomiting suggest gastric outlet obstruction.
Anorexia may occur.

5. ◑ Physical Examination:
Epigastric tenderness is the most frequent finding.
Tachycardia and orthostasis suggest dehydration secondary to vomiting or active GI blood loss.
A severely tender , boardlike abdomen suggests a perforation.

6. Differential diagnosis
1- Non-ulcer dyspepsia.
2- GERD.
3- Biliary tract disease.
4- Pancreatitis.
5- coronary and / or mesenteric vascular insufficiency.
6- Intra-abdominal neoplasms.
7- Functional bowel syndrome.
8- inflammatory bowel disease.

7. Endoscopic differentiation of benign gastric ulcer from cancer
Investigations
1- Endoscopy: Most sensitive and specific approach for
examining the upper GI tract.
- Direct visualization of mucosa, helpful in indentifying too
small or atypical lesions detected by radiography, tissue
biopsy to rule out malignancy (GU) or H. pylori,
-Determine if the ulcer is a source of bleeding.
-DU is almost never malignant and do not required biopsy.
-GU must always required biopsy in most circumstances,
because its occasionally malignant.
Biopsy urease test.
Endoscopy is indicated in all patients with “alarm symptoms”.
Endoscopic differentiation of benign gastric ulcer from cancer
Malignant GU
Benign GU
Ulcerated mass protrudes into the lumen, folds surrounding the ulcer crater are nodular , clubbing , fused, or stop short of the ulcer margin, or if the margins are overhanging , irregular, or thickened.
Smooth, regular, rounded edges, with flat , smooth ulcer base often filled with exudates.

8. Investigations - DU
Multiple DUs
Kissing DUs GU GU
Multiple GUs

9. 2- Non – invasive methods:-
Serology: detect IgG , used in diagnosis and epidemiological studies. sensitive (90%) & specific (83%).
13C-urea breath test: quick and reliable test, sensitive (97%) & specific (96%).this test suitable for testing for eradication of the organism.
Stool antigen test: sensitive (97.6%) & specific (96%).this test useful in the diagnosis of H.pylori infection and for monitoring efficacy of eradication therapy.

10. Gastric Ulcer Body of the Stomach
A 5-cm ulcer crater in the lesser curve of the stomach is depicted en face. The filling defects in the ulcer crater are caused by a blood clot from recent bleeding.

11. The goals of the ulcer therapy:- Acid Neutralizing / Inhibitory Drugs
Treatment
The goals of the ulcer therapy:-
1- Relieve symptom.
2- Heal the ulcer.
3- Cure H.pylori and Prevent recurrence.
Acid Neutralizing / Inhibitory Drugs
Antacids:
Neutralization of secreted acid with antacids constituted the main form of therapy for peptic ulcers.
They are now rarely, if ever , used as the primary therapeutic agent but instead are often used by patients for symptomatic relief of dyspepsia.
The most commonly used agent are mixtures of aluminum hydroxide and magnesium hydroxide.
aluminum hydroxide can produce constipation and phosphate depletion, magnesium hydroxide may cause loose stools.
Many of the commonly used antacids (e.g. Maalox) have a combination of both aluminum hydroxide and magnesium hydroxide in order to avoid these sode effects.
Calcium carbonate and sodium bicarbonate are potent antacids with varying levels of potential problems.

12. Cytoprotective Agent H2 Receptor Antagonists
- Four of these agents are presently available ( cimetidine, ranitidine, famotidine, nizatidine ).
Although each has different potency, all will significantly inhibit basal and stimulated acid secretion to comparable levels when used at therapeutic doses.
dosing for cimetidine is 800 mg at bed time for treatment of active ulcer with healing rate about 80% at 4 weeks.
Comparable nighttime dosing regiments are ranitidine 300 mg, famotidine 40 mg, and nizatidine 300 mg.
Proton Pump (H+, K+ -ATPase) Inhibitors
Omeprazole, esomeprazole, lansoprazole, rabeprazole, and pantoprazole are substituted benzimidazole derivatives that covalently bind and irreversibly inhibit H+, K+ -ATPase.
Esomeprazole the newest member.
Omeprazole and lansoprazole are PPIs that have been used for the longest time.
Cytoprotective Agent
Sucralfate:
complex sucrose salt in which the hydroxyl group have been substituted by aluminum hydroxide and sulfate.
Is insoluble in water and becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulcerations.
Bismuth-containing preparations:
Colloidal bismuth subcitrate CBC and bismuth subsalicylate BSS are the most widely used preperations.
Potential mechanisms include ulcer coating, prevention of further pepsin/HCl- induced damage; binding of pepsin; and stimulation of PGs , bicarbonate and mucous secretion.
Prostaglandin Analogues
Standard therapeutic dose 200 micro- gram qid
Central role in maintaing mucosal integrity and repair.

13. Regimens recommended for Eradication of H.Pylori infection
Triple therapy
1- Bismuth subsalicylate 2 tab qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid.
2- Ranitidine bismuth citrate 400 mg bid plus tetracycline 500 mg bid plus clarithromycin or metronidazole 500 mg bid
3- Omeprazole (lansoprazole) 20 mg bid (30 mg bid) plus clarithromycin 250 or 500 mg bid plus metronidazole 500 mg bid or Amoxicillin 1 g bid.
Quadruple Therapy
Omeprazole (lansoprazole) 20 mg bid (30 mg bid) daily
Bismuth subsalicylate 2 tab qid
metronidazole 250 mg bid
tetracycline 500 mg bid
Recommendations for treatment of NSAID-related mucosal injury.
Active ulcer
NSAID discontinued H2 receptor antagonist or PPI
NSAID continued PPI
Prophylactic therapy Misoprostol
PPI
selective COX-2 inhibitor
H. pylori infection eradication if active ulcer present or a past history of peptic ulcer disease.

14. Indications for surgery in PU
Emergency:
1- Perforation.
2- Hemorrhage.
Elective:
1- Complications: e.g. gastric outflow obstruction.
2- Recurrent ulcer following gastric surgery.
Complications of gastric resection or vagotomy:-
1- Dumping.
2- Bile reflux gastritis.
3- Diarrhea and maldigestion.
4- Weight loss.
5- Anemia.
6- Metabolic bone disease.
7- Gastric cancer.

15. Complications of PU 1- Hemorrhage.
2- Perforation: DU perforated more commonly than GUs, usually into peritoneal cavity and into lesser sac also occurs. Surgery usually done to close the perforation and drain the abdomen.
3- Gastric outlet obstruction: may be prepyloric, pyloric or duodenal. Occur due to active ulcer with surrounding edema or healing ulcer with following scarring.