1. PEPTIC ULCER DISEASE

3. Definitions Peptic Ulcer
An ulcer of the alimentary tract mucosa, usually in the stomach or duodenum, and rarely in the lower esophagus, where the mucosa is exposed to the acid gastric secretion.
Jejunum after operation with anastomosis with stomach
Rarely in the ileum (Meeckel’s diverticulum).
It has to be deep enough to penetrate the muscularis mucosa.

4. Gastric Mucosa & Secretions
The inside of the stomach is bathed in about two liters of gastric juice every day.
Gastric juice is composed of digestive enzymes and concentrated hydrochloric acid, which can readily tear apart the toughest food or microorganism.
The gastroduodenal mucosal integrity is determined by protective (defensive) and damaging (aggressive) factors.

5. Gastric Mucosa & Secretions
The defensive forces
Bicarbonate
Mucus layer
Mucosal blood flow
Prostaglandins
Growth factors
The aggressive forces
Helicobacter pylori
HCl acid
Pepsins
NSAIDs
Bile acids
Ischemia and hypoxia.
Smoking and alcohol
When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions and ulcerations.

6. Structural Considerations
Mechanisms that maintain mucosal integrity

7. My be acute or chronic
Both penetrate muscularis mucosae
Chronic cause fibrosis
Erosion not penetrate M M

8. GASTRIC AND DUODENAL ULCER
Decreasing in developed countries due to wide use of anti H-pylori therapy
High in developing countries
In DU: M: F ratio 5: 1 to 2:1
In GU: 2:1 or less

9. Etiology The two most common causes of PUD are:
Helicobacter pylori (some strains) infection most likely in presence of other host factors like exaggerated secretion of pro-inflammatory factors like IL -1B and also IL 6 and 10. Also if the patient is smoking. 90% of patients with DU are +ve for H. pylori while 70% of patienys with GA are +ve.
Non-steroidal anti-inflammatory drugs (NSAIDS): cause ulcer especially DU, exacerbate DU and may introduce bleeding in ulcer.
Other uncommon causes include: (not important)
Gastrinoma (Gastrin secreting tumor)
Stress ulceration (trauma, burns, critical illness)
Viral infections
Vascular insufficiency

10. Etiology – Helicobacter pylori

11. AETIOLOGY
H. Pylori:
In developed countries the incidence increase with age.
In developing countries most cases are acquired early in childhood.
Most infections are asymptomatic. Minority develop symptoms
90% of patient with DU are H. pylori positive.
70% of GU patients are positive.
Remaining 30% of GU is due to NSAIDs.

12. Pathogenesis of Helicobacter infection
Present only in gastric type mucosa
In deep layers of mucus just above the mucosal surface, Ph near neutral
Secrete urease enzyme that change the urea to ammonia making the environment around the bacterium more neutral (raise PH).
Cause inflammation (due to secretion of many inflammatory substances like cag A and vac A)

13. In most antral gastritis: D cells that produce somatostatin decrease , while gastrin that produced by G cells increased leading to increased acid production by parietal cells of the stomach.
In most cases this acid cause no problems but in exaggerated cases especially in presence of smoking it may cause duodenal ulcer.
Pathogenesis of gastric ulcer is not clear but probably h. pylori decreases the mucosal resistance to the effects of acid and pepsin.

14. In about 1% pan gastritis may occur leading to atrophic gastritis and achlorhydra which help H. pylori to persist leading to production of carcinogenic nitrates and carcinoma.

17. Etiology – NSAIDS Effect of NSAIDS
All NSAIDs reduce the mucosal production of prostaglandins from precursor membrane fatty acids.
The drugs also generate oxygen-free radicals and products of the lipoxygenase pathway that may contribute to ulceration.

18. Etiology – NSAIDS
Users of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events than nonusers.
Additional risk factors include:
Age greater than 60 years
Smoking
Previous history of GI events
Concomitant corticosteroid use. In terms of serious complications, the combination of steroids and NSAIDs leads to a 10-fold increase in GI bleeding and a 20-fold increase in GI-related death.

19. Type of NSAID and Risk of Ulcer
Etiology – NSAIDS
Type of NSAID and Risk of Ulcer
Risk Group Drug Relative Risk
Low Ibuprofen
Diclofenac
Medium Naproxen
Indomethacin
Piroxicam
High Ketoprofen
Azapropazone

20. Etiology: NSAIDS + H. pylori = ??
Are patients on NSAIDs who are also infected with H. pylori more likely than those who are not infected to have dyspepsia, mucosal damage, or ulcers?

21. Smoking: gastric ulcer more than D U, also increase complication and impair healing
Acid-pepsin versus mucosal resistance. No ulcer without acid, so not occur in atrophic gastritis and in pernicious anaemia
. Exaggerated acid secretion that follow gastrin secretion as in H. pylori infection and Zollinger Ellison syndrome cause severe duodenal ulceration.
Most duodenal ulcer patients have markedly exaggerated acid secretion in response to stimulation by gastrin, and H. pylori (as already discussed) leads to hypergastrinaemia. In gastric ulcer patients the effects of H. pylori are more complex, and impaired mucosal defence resulting from a combination of H. pylori infection, NSAIDs and smoking may have a more important role.
Gsastric ulceration is more complicated although smoking, NSAIDs and H. pylori play their role.

22. Risk factors

23. Pathology

24. Pathology Chronic gastric ulcer is usually single; 90% are situated on the lesser curve within the antrum or at the junction between body and antral mucosa. Chronic duodenal ulcer usually occurs in the first part of the duodenum just distal to the junction of pyloric and duodenal mucosa; 50% are on the anterior wall. Gastric and duodenal ulcers coexist in 10% of patients and more than one peptic ulcer is found in 10-15% of patients. A chronic ulcer extends to below the muscularis mucosae and the histology shows four layers: surface debris, an infiltrate of neutrophils, granulation tissue and collagen.

26. CLINICAL FEATURES

27. Clinical features
Peptic ulcer disease is a chronic condition with a natural history of spontaneous relapse and remission lasting for decades, if not for life. Although they are different diseases, duodenal and gastric ulcers share common symptoms which will be considered together. The most common presentation is that of recurrent abdominal pain which has three notable characteristics: localization to the epigastrium, relationship to food and episodic occurrence. Occasional vomiting occurs in about 40% of ulcer subjects; persistent daily vomiting suggests gastric outlet obstruction. In one-third of patients the history is less characteristic. This is especially true in elderly subjects under treatment with NSAIDs. In these patients pain may be absent or so slight that it is experienced only as a vague sense of epigastric unease.

28. Occasionally, the only symptoms are anorexia and nausea, or a sense of undue repletion after meals. In some patients the ulcer is completely 'silent', presenting for the first time with anaemia from chronic undetected blood loss, as an abrupt haematemesis or as acute perforation; in others there is recurrent acute bleeding without ulcer pain between the attacks. The diagnostic value of individual symptoms for peptic ulcer disease is poor; the history is therefore a poor predictor of the presence of an ulcer.

29. Peptic Ulcer Disease - Diagnosis
Diagnosis of ulcer
Diagnosis of H. pylori

30. Diagnosis of Ulcer
Endoscopy is the preferred investigation. Gastric ulcers may occasionally be malignant and therefore must always be biopsied and followed up to ensure healing.

31. Upper GI scopy. OGD (EGD),

32. Peptic Ulcer Disease - Diagnosis
Doudenal Ulcer on Endoscopy
Normal doudenal bulb
Doudenal Ulcer

33. Peptic Ulcer Disease - Diagnosis
Gastric Ulcer on Endoscopy
Chronic Gastric Ulcers

34. Peptic Ulcer Disease - Diagnosis
Duodenal Ulcer on Barium meal
Duodenal Ulcer

35. Peptic Ulcer Disease - Diagnosis
Gastric Ulcer on Barium meal
Gastric Ulcer

36. METHODS FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION

37. Many different diagnostic tests for H. pylori infection are available
Many different diagnostic tests for H.pylori infection are available . Some are invasive and require endoscopy; others are non-invasive. They vary in sensitivity and specificity. Overall, breath tests are best because of their accuracy, simplicity and non-invasiveness.

38. Diagnosis of H. pylori Tests for Helicobacter pylori Non-invasive
C13 or C14 Urea Breath Test
Stool antigen test
H. pylori IgG titer (serology)
Invasive
Gastric mucosal biopsy
Rapid Urease test

39. Diagnosis of H. pylori Tests for Helicobacter pylori
C13 or C14 Urea Breath Test

40. Diagnosis of H. pylori Tests for Helicobacter pylori
Stool Antigen test

41. Diagnosis of H. pylori
Tests for Helicobacter pylori
Mucosal Biopsy

42. Diagnosis of H. pylori Tests for Helicobacter pylori Rapid Urease Test
This test is based on the urease enzyme present in the H. pylori
Urea is split into NH3 and CO2
The change in pH causes a color change in the medium

43. Rapid office kits available Lacks sensitivity and specificity
Body_ID: B022036
22.36 METHODS FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION
NON-INVASIVE
Serology
Rapid office kits available
Lacks sensitivity and specificity
Good for population studies
Cannot differentiate current from past infection
Urea breath tests
High sensitivity and specificity
14C uses radioactivity
13C requires expensive mass spectrometer
Faecal antigen test
Cheap, accurate
Acceptability
INVASIVE (ANTRAL BIOPSY)
Histology
Sensitivity and specificity
False negatives occur
Takes several days to process
Rapid urease tests, e.g. CLO, Pyloritek
Cheap, quick Specificity
Lack sensitivity
Microbiological culture
'Gold standard'
Slow and laborious
Defines antibiotic sensitivity
Lacks sensitivity

44. Management The aims of management are to relieve symptoms, induce healing and prevent recurrence. H. pylori eradication is the cornerstone of therapy for peptic ulcers, as this will successfully prevent relapse and eliminate the need for long-term therapy in the majority of patients.

45. H. pylori eradication All patients with proven acute or chronic duodenal ulcer disease and those with gastric ulcers who are H. pylori-positive should be offered eradication as primary therapy. Treatment is based upon a proton pump inhibitor taken simultaneously with two antibiotics (from amoxicillin, clarithromycin and metronidazole) for 7 – 10 days . Success is achieved in over 90% of patients, although compliance, side-effects and metronidazole resistance influence the success of therapy.
Second-line therapy should be offered to those patients who remain infected after initial therapy once the reasons for failure of first-line therapy have been established. For those who are still colonised after two treatments, the choice lies between a third attempt with quadruple therapy (bismuth, proton pump inhibitor and two antibiotics) or long-term maintenance therapy with acid suppression.

46. COMMON SIDE-EFFECTS OF H. PYLORI ERADICATION THERAPY Diarrhoea
30-50% of patients; usually mild but Clostridium difficile-associated colitis can occur
Flushing and vomiting when taken with alcohol (metronizadole)
Nausea, vomiting
Abdominal cramp
Headache
Rash

47. H. pylori and NSAIDs are independent risk factors for ulcer disease but it is not clear whether patients requiring long-term NSAID therapy should first undergo eradication therapy to reduce ulcer risk. Current evidence suggests that this is not necessary in young, fit patients with no history of ulcer disease or dyspepsia but a 'test and treat' strategy for older patients with major comorbidity or a previous ulcer history is recommended. Subsequent co-prescription of a proton pump inhibitor along with the NSAID is advised but is not always necessary for patients being given low-dose aspirin in whom the risk of ulcer complications is lower.

48. INDICATIONS FOR H. PYLORI 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
Long-term NSAID users

49. General measures
Cigarette smoking, aspirin and NSAIDs should be avoided. Alcohol in moderation is not harmful and no special dietary advice is required.
Short-term management Many different drugs are available for the short-term management 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.

50. Peptic Ulcer Disease - Treatment
Medical Treatment of Peptic Ulcer Disease
The major agents in the current armamentarium against peptic ulcer disease are
H2-receptor antagonists
H+,K+-ATPase (acid/proton pump) inhibitors
Sucralfate
Antacids
Bismuth compounds

51. Peptic Ulcer Disease - Treatment
Sites of Drug Action in PUD

52. Peptic Ulcer Disease - Treatment
The Mechanism and side effects of various acid suppressive medications
Drug Mechanism Common side effect
Antacids neutralize acid Mg - diarrhea
Al - constipation
Ca – constipation
H2 receptor block histamine receptor cytochrome 450 altered
antagonists metabolism of drugs
Prostaglandins agonist diarrhea, cramps, abortion
H+/K+ ATPase block acid pump hypergastrinemia
inhibitors enterochromaffin cell (ECL) hyperplasia
Sucrafate coat ulcerated mucosa constipation

53. Peptic Ulcer Disease - Treatment
Misoprostol
Synthetic prostaglandin E1 analog
Inhibits gastric acid secretion
Protects the gastric mucosa
Increases bicarbonate and mucous production
Decreases pepsin levels during basal conditions
Used in prevention of NSAIDS induced gastric ulcers
Does not prevent development of duodenal ulcers
May also stimulate uterine contractions that may endanger pregnancy

54. PUD – H. pylori Treatment
Regimen Dosage Duration
Omeprazole mg BID 7 – 10 days
Clarithromycin mg BID 7 – 10 days
Amoxicillin mg BID 7 – 10 days
Ranitidine bismuth citrate (RBC) mg BID 28 days
Clarithromycin mg BID 7 – 10 days
Bismuth subsalicylate mg QID 14 days
Metronidazole mg BID 14 days
Tetracycline mg QID 14 days

55. Surgical treatment
The cure of most peptic ulcers by H. pylori eradication therapy and the availability of safe, potent acid-suppressing drugs have made elective surgery for peptic ulcer disease a rare event.

56. INDICATIONS FOR SURGERY IN PEPTIC ULCER
Emergency
Perforation
Haemorrhage
Elective
Complications, e.g. gastric outflow obstruction
Recurrent ulcer following gastric surgery

57. Peptic Ulcer Disease - Complications
Complications of PUD on Endoscopy
Bleeding DU Perforated GU Duodenal stricture