PEPTIC ULCER DISEASE

mashehabat@just.edu.jo

PUD: definition
BREAK IN THE GASTROINTESTINAL MUCOSA EXPOSED TO GASTRIC ACID and PEPSIN MORE THAN 5 mm in diameter. MAY BE ACUTE OR CHRONIC.

EROSION

A BREAK IN THE GI MUCOSA LESS THAN 5 mm IN DIAMETER - NOT PENETRATING MUSCULARIS MUCOSA MAY OCCUR IN ACID SECRETING AND NONACID SECRETING MUCOSA PERISTALSIS NOT AFFECTED HEALS RAPIDLY.

Sites of PUD
PUD may occur in any area where acid and pepsin are present Commonest sites: Duodenum especially first part duodenal bulb Stomach especially over lesser curve Other sites: Lower end of esophagus site of gastro -jejunal anastomosis Opposite to Meckels diverticulm

AETIOLOGY OF PUD
HELICOBACTER PYLORI- ASSOCIATED
ULCERS

NSAID-RELATED ULCERS.
HYPERSECRETORY STATES: Z-E SYNDROME, IDIOPATHIC.

Pathogenesis of PUD
IMBALANCE BETWEEN AGGRESIVE AND DEFENSIVE FACTORS

AGGRESSIVE FACTORS
ACID AND PEPSIN

Role of Acid in PUD

NEVER found when maximum acid output "MAO" is less than 10 mmol/hour RARE when MAO below 20 mmol/h COMMON with higher MAO rates NOT seen when fasting gastric pH is above 2.5

DEFENSIVE FACTORS
PROSTAGLANDINS MUCOSAL BLOOD FLOW MUCUS GEL LAYER HCO3 EPITHELIAL JUNCTIONS REGENERATION OF THE EPITHELIAL LAYER GROWTH FACTORS: EGF

Epidemiology of PUD
Prevalence about 5-10% Varies in different communities Higher prevalence in low socioeconomic classes and with certain diseases DU more in males: M/F: 3:1 GU equal in both sexes but increases with age FAMILY HISTORY: 3-4 increased risk . CIGARETTE SMOKING: ulceration increased EMOTIONAL DISTURBANCES and STRESS: increase gastric acid secretion

CLINICAL PICTURE OF PUD

Symptoms of PUD:
Epigastric pain dyspepsia may be asymptomatic symptoms related to complications

Signs:
epigastric tenderness signs related to complications

Diagnosis of PUD
Clinical picture is suggestive but not diagnostic Diagnosis best by endoscopy Barium meal less helpful no role for serum gastrin or gastric acid studies in usual ulcers, indicated if ZE is suspected Evaluation for H pylori infection Gastric ulcer should be biopsied to exclude malignancy

Endoscopy in PUD: GU

Ulcer

Gastric erosions

Gastric erosions

Erosive duodenitis

Erosion

Duodenal ulcer

Duodenal ulcer

Duodenal ulcer

Helicobacter pylori

Role of H.pylori in GI diseases

Healthy subjects 20-50% Chronic active gastritis 100% Duodenal ulcer >90% Gastric ulcer 50 - 80% Gastric adenocarcinoma 90% Gastric lymphoma 85%

Diagnosis of Helicobacter pylori infection

Invasive( through endoscopy)
Gastric biopsy and staining culture of Bx specimen Tests using urease enzyme in Bx specimens

Non-invasive:
Urea breath test H.pylori antibodies Stool antigen Salivary antigen

Complications of PUD
Hemorrhage Perforation Gastric outlet obstruction penetration in posterior ulcers

GI Bleeding

GI Bleeding

Ulcer with recent bleed

Ulcer Perforation

Gastric outlet obstruction

Natural history of PUD

PUD is a chronic episodic disease with relapses and remissions. If left untreated, 30-40 % of ulcers heal within 8 weeks. Recurrence rate without treatment is 70% during first year and 90% within 2 years. Complications develop in 20% of PUD

TREATMENT OF PEPTIC ULCER DISEASE

AIM OF TREATMENT:
RELIEVE SYMPTOMS HEAL THE ULCER PREVENT COMPLICATIONS PREVENT RECURRENCES

Life-style modification in PUD

Doubtful efficacy
REST RELAXATION GOOD SLEEP DIET:
bland diet freuent small meals caffeine-containing beverages role of milk fat diet spices alcohol fiber vitamin E and dietary fatty acids

HISTAMINE- RECEPTOR ANTAGONISTS (H2-Blockers )

CIMETIDINE 400mg b.d or 800mg at bed time
RANITIDINE 150mg b.d. or 300mg at bed time FAMOTIDINE 20mg b.d. or 40mg at bed time NIZATIDINE 150mg b.d. or 300mg at bed time

HISTAMINE- RECEPTOR ANTAGONISTS (H2-Blockers )

Act through blocking H2 receptors in the parietal cells Suppress nocturnal acid secretion by more than 90% Suppress 24 hour acid secretion by 50-70% Side effects : CNS effects: headache, mental confusion Reversible gynecomastia and impotence. Interaction with drugs metabolized through hepatic cytochrome P-450 microsomal enzymes

ANTACIDS
Rapid symptomatic relief Cheap Large amounts are required to heal ulcers leading to undesirable side effects. If taken on empty stomach; they are effective only for 10-20 minutes If taken one hour after meals they are effective for 2-3 hours. Tablet preparations are less effective than suspensions

Side effects of antacids

Sod bicarbonates: increases sodium load milk- alkali syndrome Aluminum compounds: constipation binds phosphates binds drugs.

Side effects of antacids

Magnesium compounds: diarrhea accumulation in renal failure Calcium compounds: constipation rebound hyperacidity

PROTON PUMP INHIBITORS(PPIs)

Suppress acid secretion by non-cometitively and irreversibly inhibiting the H+ , K+ATPase of the gastric parietal cells Inhibit over 90%of 24-hour acid secretion Increase secretion of gastrin usually 2-3 times the baseline with proliferation and growth of ECL cells No carcinoid tumours reported to occur in man due to PPIs Heal 50% of DUs by 2 weeks, 90% in 4 weeks and almost all by 6-8 weeks.

PROTON PUMP INHIBITORS(PPIs)

Omeprazole: 10, 20 mg lansoprazole: 15, 30 mg pantoprazole: 20, 40 mg rabeprazole: 10, 20 mg esomeprazole:20, 40 mg Tenatoprazole: 40 mg: longer duration of action

New Therapies
Potasium competetive acid blockers: P-CAB : Block secretion of acid by blocking exchange of K+ by H+: still investigational AZD0865

Eradication therapy for H.Pylori

In vitro HP highly suggestive to many antibiotics In vivo, sensitive to the following agents:
amoxycillin tetracyclin clarithromycin Metronidazole, tinidazole bismuth PPIs

Second line drugs: Levofloxacin, gatifloxacin, rifabutin

Eradication therapy for H.Pylori

Use triple or quadruple regimen for 7-14 days. Efficacy of the regimen depends upon drugs used, compliance of patient, resistance pattern of HP in the area Relapse rate drops to less than 10% per year after successful eradication

SUCRALFATE
1gm 4 times daily on empty stomach Healing rate: 70-80% within 8 weeks binds with the proteinaceous base of the ulcer increasing local mucosal production of PGs Side effects: constipation nausea reduces the absorption of some drugs binds phosphate in the gut

PROSTAGLANDINS
Inhibit gastric acid secretion and has cytoprotective effects They are less effective than H2- blockers side effects:
abdominal cramps diarrhea not cost-effective

Indicated for prophylactic use rather than for treatment

Surgery for PUD

Rare after introduction of effective therapeutic agents except for complications