GERD and Peptic ulcer disease August 29, 2011

Peptic Physiology

Peptic Physiology Intrinsic factor Hydrochloric acid Stimulated by gastrin, ach, H+ Mucus Bicarbonate Pepsinogen Stimulated by gastrin Primarily in antrum

Gastroesophageal Reflux Disease

Epidemiology About 44% of the US adult population have heartburn at least once a month 14% of Americans have symptoms weekly 7% have symptoms daily

Physiologic vs Pathologic Physiologic GERD Postprandial Short lived Asymptomatic No nocturnal sx Pathologic GERD Symptoms Mucosal injury Nocturnal sx --distinction between normal and GERD is blurred because some degree of reflux is physiologic is all folks Physiologic—postprandially, short lived, asymptomatic, not during sleep Pathologic—symptoms or mucosal injury and often with nocturnal symptoms

Pathophysiology Primary barrier to gastroesophageal reflux is the lower esophageal sphincter LES normally works in conjunction with the diaphragm If barrier disrupted, acid goes from stomach to esophagus --At level of diaphragmatic hiatus—main deterrant to reflux --disruption due to –review slide--multifactorial

Clinical Manifestations Most common symptoms Heartburn—retrosternal burning discomfort Regurgitation—effortless return of gastric contents into the pharynx without nausea, retching, or abdominal contractions Dysphagia—difficulty swallowing Other symptoms include: Chest pain, globus sensation, odynophagia, nausea Extraesophageal manifestations Asthma, laryngitis, chronic cough --gerd related chest pain may mimic angina—squeezing/burning, substernal, radiates to back, neck, jaw, arms. Minutes to hours. After meals, awakens patient from sleep, exacerbated by emotional stress --water brash—hypersalivation—heartburn and regurg of sour fluid or tasteless saliva into mouth --globus—lump in throat irrespective of swallowing --odynophagia—esophageal ulcer --nausea—infrequent --hrt burn 70-85%//regurg 60%//dysphagi 15-20%//angina 33%//asthma 15-20%

Diagnostic Evaluation If classic symptoms of heartburn and regurgitation exist in the absence of “alarm symptoms” the diagnosis of GERD can be made clinically and treatment can be initiated --heartburn +/- regurgitation high specificity, low sensitivity

Alarms Dysphagia Early satiety GI bleeding Odynophagia Vomiting Weight loss Iron deficiency anemia --need further eval if any present—egd--

Trial of Medications H2RA or PPI Expect response in 2-4 weeks If no response Change from H2RA to PPI Maximize dose of PPI Once established h&p dx and no alarm symptoms can proceed with dx/therapeutic trial of tx.

Trial of Medications If PPI response inadequate despite maximal dosage Confirm diagnosis EGD 24 hour pH monitor --if started with or changed to --prilo 40 qd x 14d as specific/sensitive as pH monitor --remember only works on active pumps. Take 30-60 min prior to eating

EGD Endoscopy (with biopsy if needed) In patients with alarm signs/symptoms Those who fail a medication trial Those who require long-term tx Absence of endoscopic features does not exclude a GERD diagnosis Allows for detection, stratification, and management of esophageal manifestations or complications of GERD --if trial of med did not work or if alarm symptoms or long term 5yrs need egd 1a evidence—dysphagia/early satiety/gi bleed/odynophagia/vomiting/wt loss/anemia --50-70% of patient’s with gerd will have a neg egd.

24-hour pH monitoring Accepted standard for establishing or excluding presence of GERD for those patients who do not have mucosal changes Trans-nasal catheter or a wireless, capsule shaped device --Transnasal catheter or a wireless capsule shaped device affixed to distal esophagus --cather positioned 5cm above manometrically defined upper limit of les --capsul attached 6cm proximal to endoscopically defined squamocolumnar jxn --if mucosal changes—have dx and do not need 24hph.

Patient with heartburn Initiate tx with H2RA or PPI H2RA taken BID PPI taken QD No Good response No Good response Yes Yes Yes Increase to max dose QD or BID Maintenance therapy with lowest effective dose Frequent relapses No Yes On demand tx Symptoms persist Good response No Consider EGD if risk factors present (> 45, white, male and > 5 yrs of sx) Confirm diagnosis EGD, ph monitor

Treatment Goals of therapy Symptomatic relief Heal esophagitis Avoid complications

Lifestyle modifications Avoid large meals Avoid acidic foods (citrus/tomato), alcohol, caffeine, chocolate, onions, garlic, peppermint Decrease fat intake Avoid lying down within 3-4 hours after a meal Elevate head of bed 4-8 inches Avoid meds that may potentiate GERD (CCB, alpha agonists, theophylline, nitrates, sedatives, NSAIDS) Avoid clothing that is tight around the waist Lose weight Stop smoking

Medical Treatment Antacids Over the counter acid suppressants and antacids appropriate initial therapy Approx 1/3 of patients with heartburn-related symptoms use at least twice weekly More effective than placebo in relieving GERD symptoms --Tums, rolaids, maalox --$1 billion in yearly expenditures --aluminum/calcium—constipation Mag--diarrhea

Medical Treatment Histamine H2-Receptor Antagonists More effective than placebo and antacids for relieving heartburn in patients with GERD Faster healing of erosive esophagitis when compared with placebo Can use regularly or on-demand

Medical Treatment AGENT EQUIVALENT DOSAGE DOSAGES Cimetadine 400mg twice daily 400-800mg twice daily Tagamet Famotidine 20mg twice daily 20-40mg twice daily Pepcid Nizatidine 150mg twice daily 150mg twice daily Axid Ranitidine 150mg twice daily 150mg twice daily zantac --otc dose uniformly half of standard lowest prescription dose --similar clinical efficacy

Medical Treatment Proton Pump Inhibitors Better control of symptoms with PPIs vs H2RAs and better remission rates Faster healing of erosive esophagitis with PPIs vs H2RAs

Treatment AGENT EQUIVALENT DOSAGE DOSAGES Esomeprazole 40mg daily 20-40mg daily Nexium Omeprazole 20mg daily 20mg daily Prilosec Lansoprazole 30mg daily 15-10md daily Prevacid Pantoprazole 40mg daily 40mg daily Protonix Rabeprazole 20mg daily 20mg daily Aciphex --no significant differences in symptomatic tx of GERD or healing of erosive esophagitis 1a evidence --works only on active pumps—take 30-60min prior to meals --long-term tx generally benefits outweigh risks

Treatment Antireflux surgery Failed medical management Patient preference GERD complications Medical complications attributable to a large hiatal hernia Atypical symptoms with reflux documented on 24-hour pH monitoring candidacy --esophagitis—by egd --need normal manometry/motility --partial response to acid suppression --reduce hh, repair diaphragm, strengthen ge jxn—antireflux barrier --75-90% effective at alleviating hrtburn/regurg --better at helping with hrtburn/regurg than atypical sx

Treatment Antireflux surgery candidates EGD proven esophagitis Normal esophageal motility Partial response to acid suppression

Treatment Antireflux surgery Tenets of surgery Reduce hiatal hernia Repair diaphragm Strengthen GE junction Strengthen antireflux barrier via gastric wrap 75-90% effective at alleviating symptoms of heartburn and regurgitation

Nissen Fundoplication

Upper GI Study

Treatment Endoscopic treatment Three categories Relatively new No definite indications Select well-informed patients with well-documented GERD responsive to PPI therapy may benefit Three categories Radiofrequency application to increase LES reflux barrier Endoscopic sewing devices Injection of a nonabsorbable polymer into LES area

Complications Erosive esophagitis Stricture Barrett’s esophagus --dysphagia, odynophagia, early satiety, gi bleed, anemia, vomit, wt loss

Complications Erosive esophagitis Responsible for 40-60% of GERD symptoms Severity of symptoms often fail to match severity of erosive esophagitis --black arrow squamo-columnar jxn—Z-line --Z-line has undulating smooth contours --green arrow—gastric columnar epithelium above round black sphincter --red arow—pink white esophageal squamous epithelium --ulcerations in 2-7%

Complications Esophageal stricture Result of healing of erosive esophagitis May need dilation 4-20% of patients

Complications Barrett’s Esophagus Columnar metaplasia of the esophagus Associated with the development of adenocarcinoma --1950—Norman Barrett --10-15% --black arrow squamo-columnar jxn—Z-line --Z-line has undulating smooth contours --green arrow—gastric columnar epithelium above round black sphincter --red arow—pink white esophageal squamous epithelium --RFs—male, smoker, age, obese

Complications Barrett’s Esophagus Acid damages lining of esophagus and causes chronic esophagitis Damaged area heals in a metaplastic process and abnormal columnar cells replace squamous cells This specialized intestinal metaplasia can progress to dysplasia and adenocarcinoma Adenoca with barretts 0.5%/yr--------without barretts 0.07%/yr

Complications Barrett’s Esophagus Manage in same manner as GERD EGD every 3 years in patient’s without dysplasia In patients with dysplasia annual to shorter interval surveillance Many patients with Barrett’s are asymptomatic

Complications Esophageal dysplasia/cancer Cancer High-grade dysplasia Esophagectomy High-grade dysplasia Esophagectomy or ablation Low-grade dysplasia Treat GERD EGD surviellence 35

Peptic Ulcer Disease

Peptic Ulcer Disease Symptoms Pain Bleeding Perforation Obstruction

Peptic Ulcer Disease

Duodenal Ulcer Usually within 2 cm of the pylorus Pain cyclical 1-2 hours after breakfast, lunch and at night Etiology H pylori - 90% NSAIDs – 10% Increased vulnerablity of mucosa to acid and pepsin

Duodenal Ulcer Eridicate H pylori Surgery for complications Triple therapy PPI – twice daily for 2 weeks Amoxicillin - 1g twice daily for 2 weeks Clarithromycin – 500mg twice daily for 2 weeks Surgery for complications Bleeding Perforation Obstruction

Duodenal Ulcer

Zolliger-Ellison Syndrome (Gastrinoma) Very rare MEN-1 Tumor of islet cell Produce gastrin – lab levels extreme Typically in wall of duodenum or pancreas Gastrinoma Triangle Ulcers Usually multiple In 2nd-3rd portion of duodenum Treatment PPI Surgical resection

Gastric Ulcer Types Type I Type II Type III Most common Lesser curve H pylori Type II Pre pyloric Associated with duodenal ulcers Type III Antrum NSAIDs

Gastric Ulcer Need to rule out malignancy Treatment EGD Biopsy Stop NSAIDs PPI Treat H pylori Repeat EGD to check for healing Surgery Malignancy Bleeding Perforation Obstruction

Questions?