Ahmad Hormati Assistant Professor of Gastroenterology Qom University of Medical Sciences.

PEPTIC ULCER DISEASE

Objectives  Definition of peptic ulcer  Comparison of duodenal & gastric ulcers  etiology  Clinical presentation  Management  Emergency scenario

What is a peptic ulcer?

Peptic ulcer  refers to erosion of the mucosa lining any portion of the G.I. tract.  It is defined as : A circumscribed ulceration of the gastrointestinal mucosa occurring in areas exposed to acid and pepsin and most often caused by Helicobacter pylori infection. (Uphold & Graham, 2003)  gastric ulcer : the ulcer that occurs in the stomach lining,some of them may be malignant  duodenal ulcer : most often seen in first portion of duodenum (>95%) Peptic Ulcer Disease (PUD) Definition

Normal Esophagus & Stomach

Protective factors vs. hostile factors Peptic Ulcer Disease Pathogenesis :

A) Normal B) Increased Attack * Hyperacidity Etiology of PUD A) Normal B) Increased Attack * Hyperacidity*Pepsin.*NSAIDs. C) Weak defense * Helicobacter pylori * Stress, drugs, smoking

Peptic ulcer disease

Peptic Ulcer Disease Pathogenesis :

Alarm symptoms  In addition to increasing age, the following "alarm symptoms" raise the suspicion of gastric malignancy, although their accuracy in predicting or excluding malignancy remains unsettled :  Unintended weight loss  Persistent vomiting  Progressive dysphagia  Odynophagia  Otherwise unexplained anemia or iron deficiency  Hematemesis  Palpable abdominal mass or lymphadenopathy  Family history of upper gastrointestinal cancer  Previous gastric surgery  Jaundice

duodenal sites are 4x as common as gastric sites duodenal sites are 4x as common as gastric sites most common in middle age with peak years most common in middle age with peak years Male to female ratio—4:1 Male to female ratio—4:1 Genetic link: 3x more common in 1st degree relatives Genetic link: 3x more common in 1st degree relatives more common with blood group O more common with blood group O associated with increased serum pepsinogen associated with increased serum pepsinogen H. pylori infection common,up to 95% H. pylori infection common,up to 95% smoking is twice as common smoking is twice as common common in late middle age. common in late middle age. incidence increases with age. incidence increases with age. Male to female ratio—2:1 Male to female ratio—2:1 More common with bl. group A More common with bl. group A Use of NSAIDs: associated with a three- to four-fold increase in risk of gastric ulcer Use of NSAIDs: associated with a three- to four-fold increase in risk of gastric ulcer Less related to H. pylori than duodenal ulcers : about 80% Less related to H. pylori than duodenal ulcers : about 80% % of patients with a gastric ulcer have a concomitant duodenal ulcer % of patients with a gastric ulcer have a concomitant duodenal ulcer Duodenal Ulcer Vs. Gastric Ulcer

Duodenal vs Gastric DUODENALGASTRIC INCIDENCEMore commonLess common ANATOMYFirst part of duodenum – anterior wall Lesser curvature of stomach DURATIONAcute or chronicChronic MALIGNANCYRareBenign or malignant

The causes of peptic ulcer disease include the following:  Infection with the bacteria Helicobacter pylori occurs in 80 to 95% of patients with peptic ulcer disease. H. pylori infection impairs the protective mechanisms of the G.I. tract against low pH and digestive enzymes and leads to ulceration of the mucosa.  Stress — Emotional, trauma, surgical.  Injury or death of mucus-producing cells.  Excess acid production in the stomach. The hormone gastrin stimulates the production of acid in the stomach; therefore, any factors that increase gastrin production will in turn increase the production of stomach acid.  Drugs: Chronic use of aspirins and NSAIDs, or Corticosteroids Peptic Ulcer Disease Causes:

Risk factors  HELICOBACTER PYLORI  Non Steroidal Anti-inflammatory Drugs  Steroid therapy  Smoking  Excess alcohol intake  Genetic factors  Zollinger Ellison syndrome – rare syndrome caused by gastrin-secreting tumour  Blood group O  Hyperparathyroidism

H Pylori  Urease producing, gram negative bacillus  Developing countries  Infection increases with age  Infects mucosa of stomach > inflammatory response > gastritis > increased gastrin secretion > gastric metaplasia > damage to mucosa > ulceration  Increased risk of developing gastric adenocarcinoma

 Most common infection in the world (20%)  10% of men, 4% women develop PUD  Positive in % of PUD patients.  H.pylori related disorders:  Chronic gastritis – 90%  Peptic ulcer disease – %  Gastric carcinoma – 70%  Gastric lymphoma  Reflux Oesophagitis.  Non ulcer dyspepsia Helicobacter pylori: No acid No ulcer OLD TESTAMENT No HP No ulcer NEW TESTAMENT

Helicobacter pylori:  Gram negative, Spiral bacilli  Spirochetes  Do not invade cells – only mucous  Breakdown urea - ammonia  Break down mucosal defense  Chronic Superficial inflammation

H pylori testing  C urea breath tests  Stool antigen tests  Serology  Endoscopy with biopsy

Urease Breath Test.

Differential diagnoses for epigastric pain  Surgical  Biliary colic, acute cholecystitis  Pancreatitis  Perforation of viscus  Acute appendicitis  Malignancy  Medical  GORD  MI  PE  Pneumonia

Symptoms of PUD  Asymptomatic  Epigastric pain  Nausea  Oral flatulence, bloating, distension and intolerance of fatty food  Heartburn  Pain radiating to the back

ALARM signs for epigastric pain  Chronic GI bleeding  Iron-deficiency anaemia  Progressive unintentional weight loss  Progressive dysphagia  Persistent vomiting  Epigastric mass  Patients aged 55 years and older with unexplained and persistent recent- onset dyspepsia alone

Manifestations of peptic ulcer disease: Episodes of remission and exacerbation Pain that for duodenal ulcers is often relieved by eating or antacids G.I. bleeding and possible hemorrhage (20 to 25% of patients) Perforation of ulcers with significant mortality Obstruction of G.I. tract Peptic Ulcer Disease Manifestations:

 Endoscopy  Barium meal – contrast x-ray  Biopsy – bacteria & malignancy  H.Pylori:  Endoscopy cytology  Biopsy – Special stains  Culture - difficult  Urease Breath test. PUD - Diagnosis

 Bleeding – Chronic, Acute, Massive  Fibrosis, Stricture obstruction – pyloric stenosis.  Perforation – Peritonitis- emergency.  Gastric carcinoma. (not duodenal carcinoma) PUD – Complications

Non-pharmacological Treatment of Peptic ulcer 1-Avoid spicy food. 2-Avoid xanthin containing beverges. 3-Avoid Alcohol. 4-Avoid Smoking. 5-Avoid heavy meals. 6-Encourage small frequent low caloric meals. 7-Avoid ulcerating drugs e.g. NSAIDs, corticosteroids, xanthines and parasympathomimetics

Triple therapy for 14 days is considered the ttt of choice.  Proton Pump Inhibitor + clarithromycin and amoxicillin Omeprazole (Prilosec): 20 mg PO bid for 14 d or Lansoprazole (Prevacid): 30 mg PO bid for 14 d or Rabeprazole (Aciphex): 20 mg PO bid for 14 d or Esomeprazole (Nexium): 40 mg PO qd for 14 d plus Clarithromycin (Biaxin): 500 mg PO bid for 14 and Amoxicillin (Amoxil): 1 g PO bid for 14 d Can substitute Flagyl 500 mg PO bid for 14 d if allergic to Penicillin.  In the setting of an active ulcer, continue on proton pump inhibitor therapy for additional 2 weeks.  Goal: complete elimination of H. Pylori. Once achieved reinfection rates are low. PUD –Treatment

FUNCTIONAL DYSPEPSIA

DEFINITION  An international committee of clinical investigators developed the following revised definition (Rome III criteria) of functional dyspepsia for research purposes, which can also be applied to clinical practice:  One or more of:  Bothersome postprandial fullness  Early satiation  Epigastric pain  Epigastric burning  AND  No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms.  These criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis.

Treatment  We suggest patients be reassured and given dietary and psychosocial advice as needed (Grade 2C).Grade 2C  We suggest that patients who do not respond to the above be given a trial of acid suppression (Grade 2B).Grade 2B  The benefit of acid suppression may be greatest in those who have reflux-like symptoms. We suggest a four- to eight-week trial of a proton pump inhibitor

Treatment  H. pylori eradication benefits only a minority of patients.  Guidelines issued by the American Gastroenterological Association and the American College of Gastroenterology recommend H. pylori eradication in patients with functional dyspepsia emphasizing a possible short-term benefit (number needed to treat around 17) and a possible long-term benefit  However, because of potential side effects of therapy, we suggest the decision to eradicate H. pylori consider the individual patient's clinical features, including response to other therapy and psychological factors (Grade 2B).Grade 2B

Treatment  Some patients may respond to an antidepressant drug. We suggest an antidepressant trial for patients in whom PPI therapy has failed, especially if there is insomnia, which might also respond (Grade 2C).Grade 2C  We generally use a tricyclic antidepressant drug or trazodone, starting with a low dose (eg, amitriptyline 10 mg at bedtime, desipramine 25 mg at bedtime, or trazodone 25 mg at bedtime) and increasing after a few days, usually to only two or three times these doses. trazodone amitriptylinedesipramine

Treatment  Prokinetics can occasionally help.  However, access to cisapride is highly restricted in the United States and many other countries. Domperidone is not marketed in the United States and metoclopramide often causes side effects.Domperidonemetoclopramide  We generally limit a trial of metoclopramide (5 to 10 mg three times daily one-half an hour before meals and at night for about four weeks) to young patients in whom other therapies have failed.  Herbal therapies continue to be investigated; we do not use them.

Rockall score