PEPTIC ULCER DISEASE

1. PEPTIC ULCER DISEASE • Dr.Omar Alsherif • Dr.Maher Maurice

2. HISTORY • William Prout (1785-1850) • 1823 he discovered that gastric juice contains HCL

3. HISTORY • William beaumont (1785-1853) • The father of gastric physiology • 1825 he studied the stomach of a patient who was injured by gunshot to his stomach

4. HISTORY • Theodor Billroth (1829 - 1894) • Life is inconstant without stomach • 1881 the first successful gasterctomy

5. HISTORY • John Sydney Edkins (1863 - 1940) • 1905 he described a chemical agent in the antrum that stimulates gastric acid secretions • “Gastrin”

6. HISTORY • 1910 Karl Schwarz publishes the excess acid theory • “KEINE SÄURE KEIN GESCHWÜR”

7. “NO ACID NO ULCER”

8. EPIDEMIOLOGY • PUD affects ≃ 4.5 million people in the US annually • The hospitalization rate of PUD is ≃ 30 patients per 100’000 cases • The prevalence is approximately 10-15% in ♂ and 8-10% in ♀ • It is predominantly associated with H.pylori and NSAIDs

9. ANATOMY • Grossly it is divided into three parts: • Fundus • Body • Pylorus

10. ANATOMY • Histologicaly: • Mucosa • Submucosa • Muscularis • Serosa

11. ANATOMY • Blood supply: • Left gastric • Right gastric • Short gastric • Left gastroepiploic • Right gastroepiploic

12. ANATOMY • Nerve supply: • Sympathetic (sympathetic trunk) • Parasympathetic (vagus nerves)

13. PHYSIOLOGY • Function of the stomach • Initiates the digestion of proteins • Kills bacteria • Passes the partially digested food (chyme) to the small intestine

14. PHYSIOLOGY • Gastric glands cells: • Mucus cells: mucus & HCO₃⁻ • Chief cells: pepsinogen • G cells: hormone gastrin • Enterochromaffin-like (ECL) cells: histamine & serotonin • Parietal cells: HCL & intrinsic factor • D cells: hormone somatostatin

15. PHYSIOLOGY • Regulation of gastric function • Cephalic phase: refers to control by the brain via the vagus nerves. Activation of the vagus nerves stimulates the parietal and the chief cells to produce HCl and pepsinogen respectively • Gastric phase: started after the arrival of food to the stomach by two mechanisms • Distention of the stomach • The chemical nature of the chyme • Intestinal phase: inhibition of the gastric activity when the chyme enters the small intestine

17. PHYSIOLOGY

18. PHYSIOLOGY

19. PHYSIOLOGY

20. DEFINITION • Peptic ulcers are defects in the gastric, duodenal or esophageal mucosa that extend through the muscularis mucosa and may reach the submucosa

21. PATHOPHYSIOLOGY • A variety of factors may contribute to the development of PUD. However, the final common pathway to ulcer formation is acid-peptic injury to the mucosa due to breach of the defense mechanism • H.pylori infection • Drugs (NSAIDs) • Life style and physiological stress • Hypersecretory states

22. HELICOBACTER PYLORI • 50% of the world’s population is infected with H.pylori • With specialized flagella and a rich supply of urease, H.pylori is uniquely equipped for survival in the hostile environment of the stomach • The flagella aids the bacteria to navigates through the mucus layer to the apical membrane of the surface epithelial cells for attachment • The enzyme urease which converts urea into ammonia and bicarbonate, thus creating an environment around the bacteria that buffers the acid secreted by the stomach. Moreover, ammonia damages the surface epithelial cells • Suerbaum S, et al. H.pylori infection. N Engl J Med. 2002; 347:1175

23. HELICOBACTER PYLORI • H.pylori is associated with decrease level of somatostatin ➔ hypergastrinemia ➔ parietal cell hyperplasia ➔ hyperacidity more acid emptying to the duodenum ➔ gastric metaplasia in the postpyloric duodenum ➔ H.pylori colonization in the duodenum • The risk of duodenal ulcer then will increase to 50 fold in those particular patients • Pietroiusti A, et al. H.pylori duodenal colonization is a strong risk factor for the development of duodenal ulcer. Aliment Pharmacol Ther. Apr 1 2005;21(7):909-15

24. HELICOBACTER PYLORI • Another mechanism whereby H.pylori can induce gastroduodenal mucosal injury is by toxin productions (vacA & cagA) which will lead to local elaboration of cytokines by infected mucosa, recruitment of inflammatory cells & release of inflammatory mediators, recruitment and activation of local immune factors, and increase apoptosis

25. NSAIDs • NSAIDs inhibit enzyme cyclooxygenase which leads to formation of prostaglandin • Prostaglandin E₂ (PGE₂) decreases gastric acid secretion and increases gastric mucus production • NSAIDs ultimately will interfere with the stomach defense mechanism

26. NSAIDs • The prevalence of PUD in chronic NSAID users is about 25% • Bleeding and perforation are more common in patients using NSAID with PUD. More than 1/2 of them report the chronic use of NSAID • Many of these patients remain asymptomatic until they develop life threatening complication • Elderly patient > 60 yrs taking NSAIDs has 10 times risk of undergoing an operation due to GI complication

27. NSAIDs • Factors that clearly put patients at increase risk for NSAID induced GI complications • Age over 60 • High dose of NSAID or acetylsalicylic acid • History of acid/peptic ulcer • Concurrent steroid intake • Concurrent anticoagulant intake • Laine L, et al. Risk factors for NSAID-associated upper GI clinical events in a long term prospective study of 34’701 arthritis patients. Aliment Pharmacol ther. Nov 2010;32(10):1240-8

28. LIFE STYLE • Smokers are about twice as likely to develop PUD as nonsmokers • Smoking increases gastric acid secretion and it decreases both gastroduodenal prostaglandin production and pancreaticoduodenal HCO₃⁻ production • It has been noticed that both physiological and psychological stress play a role in the development of PUD • Curling described duodenal ulcer in burn patients (Curling ulcer) • Cushing described PUD in patients with head trauma (Cushing’s ulcer) • Alcohol is commonly mentioned as a risk factor for PUD but confirmatory data are lacking • Aldoori WH, et al. A prospective study of alcohol, smoking, caffeine, and the risk of duodenal ulcer in men. Epidemiology. Jul 1997;8(4)420-4 • Sonnenberg A, et al. Predictors of duodenal ulcer healing and relapse. Gastroenterology. Dec 1981;81(6):1061-7 • Koivisto TT, et al. Effect of somking on gastric histology in H.pylori positive gastritis. Scand J Gasrtoenterol. 2008;43(10):1177-83

29. HYPERSECRETORY STATES • Zollinger-Ellison syndrome caused by a non-beta islet cells (gastrin secreting tumor of the pancreas)stimulates parietal cells to maximum activity which will leads to gastroduodenal ulcers • It may occur sporadically 80% or as a part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN 1) 20%, which consistent with pituitary, parathyroid, and pancreatic tumor • Patients with MEN I usually have multiple gastinomas and surgical cure is unusual. On the other hand, > 90% of patients with sporadic gastinoma will be cured after complete resection • 50-60% of gastinomas are malignant • Five year survival in patient with metastatic disease is < 40%

30. COMPLICATIONS • Bleeding • Perforation • Gastric outlet obstruction

31. BLEEDING • Most peptic ulcer related deaths in US are due to bleeding • It is the most common cause of GIT bleeding in patients admitted to hospital • 75% of patients who come to hospital with bleeding peptic ulcer disease will stop bleeding if given acid suppression and kept NPO • However, 25% will continue to bleed or will rebleed after initial quiescent period and virtually all mortalities and all the operations for bleeding occur in this group • Dallal HJ, et al. Clinical review: Upper gastrointestinal hemorrhage. BMJ. 2001;323:1115

32. Other • Cancer • Dieulafoy’s lesions • Aortoduodenal fistula • Hemobilia BLEEDING

33. BLEEDING • Forrest classification of upper GI hemorrhage • Acute hemorrhage (Forrest I) • Forrest I a (spurting hemorrhage) • Forrest I b (oozing hemorrhage) • Signs of recent hemorrhage (Forrest II) • Forrest II a (visible vessel) • Forrest II b (adherent clot) • Forrest II c (hematin on ulcer base) • Lesions without active bleeding (forrest III) • Forrest III (lesions without signs of recent hemorrhage)

34. BLEEDING • The factors that will determine the outcome of bleeding PUD are • The magnitude of hemorrhage • Comorbidities • Age > 60 yrs • Endoscopic findings (stigmata of active bleeding) • Clinical presentation (shock) • Hematemesis • Transfusion requirement > five units in 24 hrs • The Glasgow Blatchford score is used prior to endoscopy to identified high risk patients who may rebleed or ultimately will under went surgery. Patients who score higher than 6 are grouped as high risk patients • Gralnek IM, et al. Management of acute bleeding from peptic ulcer. N Engl J Med. 2008;359:928

35. BLEEDING Glasgow Blatchford Score

36. PERFORATION • It usually presents as acute abdomen • Chemical peritonitis develops from gastric or duodenal secretions, but within hours bacterial peritonitis supervenes • Sometimes perforation can be sealed spontaneously • If diagnosis have been made surgery is a must unless objective evidence that the leak has sealed i.e. Radiological contrast study, and in the absence of clinical peritonitis

37. GASTRIC OUTLET OBSTRUCTION • More than 5% of patients with PUD will present to hospital due to gastric outlet obstruction • It may be acute due to inflammation and swelling of mucosa or chronic • Most patient will require intervention either balloon dilatation or surgery • Cancer must be ruled out because most of the patients with symptoms of gastric outlet obstruction will have pancreatic, gastric, or duodenal cancer

38. CLINICAL PRESENTATION • Its is difficult to differentiate between gastric & duodenal ulcer clinically • Epigastric pain gnawing or burning sensation • Gastric: shortly after meal • Duodenal: 2-3 hours after meal • Pain get relieved by using antacids • Duodenal ulcer usually awakens patient from sleep at night while gastric ulcer does not • Patients with gastric outlet obstruction may have fullness, bloating, nausea and vomiting several hours after food intake • Other symptoms: • Dyspepsia • Heartburn • Hematemesis or melena • Hematochezia • Symptoms of anemia e.g fatigue, palpitations, dyspnea, chest discomfort

39. CLINICAL PRESENTATION • Pallor • Tachycardia • Hypotension • Fever • Mild epigastric tenderness to generalized tenderness, guarding & rigidity • PR ➡ Melena or hematochezia

40. DIFFERENTIAL DIAGNOSIS • Esophagitis • Ruptured esophagus (Boerhaave syndrome) • Acute gastroentritis • Gastritis • Duodenitis • Biliary • Cholelithiasis • Cholecystitis • Cholangitis • GERD • Viral hepatitis • Pancreatitis • Zollinger-Ellison syndrome • IBD • Irritable bowel disease • Acute coronary syndrome • AAA

41. INVESTIGATIONS • Blood • CBC • RFT • LFT • S.Amylase • S.Lipase • Coag. profile • X-Matching • Radiology • CXR • CT + IV & oral contrast 97% sensitive to site of perforation • CT angiography is essential in patient with massive GI bleeding who can not tolerate endoscopy it can detect bleeding rate of 0.4 ml/min

42. INVESTIGATIONS • Upper GI endoscopy • Therapeutic • Diagnostic • Highly sensitive for differentiation between gastric & duodenal ulcer • Allows biopsy & brush cytology • Allows for detection of H.pylori • Gastric ulcers appear as discrete mucosal lesions with a punched-out smooth base usually filled with whitish fibrinoid exudate. Ulcers tend to be solitary, well circumscribed and around 0.5-2.5 cm in diameter. They tend to occur mostly at the lesser curvature. While malignant ulcers usually have irregular heaped up or overhanging margins. The ulcerated mass often protrudes into the lumen, and the folds surrounding the ulcer crater are often nodular and irregular

43. INVESTIGATIONS • Upper GI endoscopy • More than 95% of duodenal ulcers are found in the first part of the duodenum. Most of them less than 1 cm in diameter. They are characterized by the presence of well demarcated break in the mucosa that may extend into the muscularis propria

45. INVESTIGATIONS • Other tests • Urea breath test (expensive) • Antibody test for H.pylori (less sensitive) • Fecal H.pylori antigen test (more sensitive) • Serum gastrin level • Should be obtained in certain situations to screen for Zollinger-Ellison syndrome • Multiple ulcers • Peptic ulcer associated with diarrhea, steatorrhea or weight loss • PUD associated with hypercalcemia or renal stones • Ulcer not treated with medical therapy • Ulcer occurring distal to duodenal bulb • Secretin stimulation test • Helps to distinguish Z-E syndrome from other causes of hypergastrinemia e.g. Renal failure, gastric outlet obstruction

46. TREATMENT • Treatment depends on etiology & clinical presentation • Patients who have simple PUD, eradication of H.pylori should be established even with -ve CLO test. Medication should be given for 14 days • Triple therapy • PPI e.g. Omeprazole 20 mg PO bid, followed by maintenance dose for 6 - 8 weeks • Clarithromycin 500 mg PO bid • Amoxicillin 1 g PO bid or in case of allergy metronidazole 400 mg PO tid • Quadraple therapy (pylera) • Ranitadine 150 mg PO bid, followed by maintenance dose for 6 - 8 weeks • Bismuth 525 mg PO qid • Metronidazole 400 mg PO tid • Tetracycline 500 mg PO qid • Singh V, et al. Drug resistance pattern and clonality in H.pylori strains. J Infect Dev Ctries. Mar 1 2009;3(2):130-6

47. TREATMENT • The American Collage of Gastroentrology guidelines for prevention of NSAIDs related ulcer complications • Test for H.pylori if positive should be treated • Stop NSAIDs immediately • For patients who must continue with their NSAIDs e.g. RA, PPI maintenance is recommended for 6-8 weeks. Or change to COX-2 selective inhibitors • For patients with PUD whom NSAID use is unavoidable e.g. IHD on aspirin. Maintain the lowest does possible with the use of PPI

48. TREATMENT • Complicating situations • Bleeding • Perforation • Obstruction • Non healing ulcer • Gastric cancer should always be considered in patients with gastric ulcer or gastric outlet obstruction. At lest 7 biopsies should be taken

49. BLEEDING • Initial management (ABC) • Secure airway (massive bleeding consider intubation) • Maintain breathing • Insure good IV access • Start with crystalloid, 2 L should be given initially but if the patient did not respond consider blood transfusion • CVP to monitor such resuscitation especially in elder patients • NGT suction helps to keep stomach empty and contracted • IV PPI should be started immediately as it reduces mortality, incidence of rebleeding, and the need for surgical intervention • 80 mg blous then 8 mg/h infusion for 72 hrs, then 40 mg/day orally for 1 week (1) • Low dose IV PPI can achieve the same efficacy as high dose PPI following endoscopic hemostasis (2) • (1) Tajima A, et al. PPI and recurrent bleeding in PUD. J Gastroenterol Hepatol. Dec 2008;23 Suppl 2:S237-41 • (2) Liu-Cheng, et al. Meta-analysis: High-dose vs low-dose PPI for upper gastrointestinal bleeding. World J Gastroenterol. May 2010;16(20):2558-65

50. BLEEDING • Endoscopy • Transcatheter embolization • Oversewing of a bleeding ulcer • Definitive surgery