Peptic ulcer disease

PEPTIC ULCER DISEASE

Definitions
Peptic UlcerAn 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 stomachRarely in the ileum (Meeckel’s diverticulum). It has to be deep enough to penetrate the muscularis mucosa.

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.

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.

Gastric Mucosa & Secretions

Structural Considerations
Mechanisms that maintain mucosal integrity


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

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


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
Etiology

Etiology – Helicobacter pylori Helicobacter pylori

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.


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)


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.


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.


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.

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.

Etiology – NSAIDS Type of NSAID and Risk of Ulcer Risk Group Drug Relative Risk Low Ibuprofen 2.0 Diclofenac 4.2 Medium Naproxen 9.1 Indomethacin 11.3 Piroxicam 13.7 High Ketoprofen 23.7 Azapropazone 31.5

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?

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.

Risk factors

Pathology



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.

CLINICAL FEATURES

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.

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.

Peptic Ulcer Disease - Diagnosis

Diagnosis of ulcer Diagnosis of H. pylori

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.

Upper GI scopy. OGD (EGD),

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

Gastric Ulcer on Endoscopy

Peptic Ulcer Disease - Diagnosis
Chronic Gastric Ulcers

Duodenal Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis
Duodenal Ulcer

Gastric Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis
Gastric Ulcer

METHODS FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION

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.

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
Diagnosis of H. pylori

Tests for Helicobacter pylori C13 or C14 Urea Breath Test

Diagnosis of H. pylori

Tests for Helicobacter pylori Stool Antigen test

Diagnosis of H. pylori

Tests for Helicobacter pylori Mucosal Biopsy

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
Diagnosis of H. pylori

22.36 METHODS FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION

Body_ID: B022036
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, quickSpecificity
Lack sensitivity
Microbiological culture
'Gold standard'
Slow and laborious


Defines antibiotic sensitivity
Lacks sensitivity


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.

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.

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

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.

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

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.


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

Peptic Ulcer Disease - Treatment

Peptic Ulcer Disease - Treatment
Sites of Drug Action in PUD

The Mechanism and side effects of various acid suppressive medicationsDrugMechanismCommon side effectAntacidsneutralize acidMg - diarrheaAl - constipationCa – constipationH2 receptor block histamine receptorcytochrome 450 altered antagonistsmetabolism of drugs Prostaglandinsagonistdiarrhea, cramps, abortionH+/K+ ATPase block acid pumphypergastrinemiainhibitors enterochromaffin cell (ECL) hyperplasiaSucrafatecoat ulcerated mucosaconstipation 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

Peptic Ulcer Disease - Treatment

Regimen DosageDurationOmeprazole 20 mg BID7 – 10 daysClarithromycin 500 mg BID7 – 10 daysAmoxicillin1000 mg BID7 – 10 daysRanitidine bismuth citrate (RBC) 400 mg BID28 daysClarithromycin500 mg BID7 – 10 daysAmoxicillin1000 mg BID7 – 10 daysBismuth subsalicylate 525 mg QID14 daysMetronidazole500 mg BID14 daysTetracycline500 mg QID14 days PUD – H. pylori Treatment

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.

INDICATIONS FOR SURGERY IN PEPTIC ULCER

Emergency
Perforation Haemorrhage
Elective
Complications, e.g. gastric outflow obstruction Recurrent ulcer following gastric surgery


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