Gastroesophageal Reflux Disease( GERD) Dr. SAPTINO MIRO, SpPD BAGIAN ILMU PENYAKIT DALAM FK-UNAND/RS.M.DJAMIL PADANG

Pendahuluan GER ( refluks gastroesofageal ) adalah fenomena yang dapat timbul sewaktu-waktu pada populasi umum , terutama sehabis makan dan kemudian kembali seperti normal  refluks fisiologis. Dikatakan patologis (GERD) bila terjadi refluks berulang dalam waktu lama sehingga menim bulkan keluhan/kerusakan mukosa esofagus Terdapat peningkatan prevalensi GERD

Epidemiologi Di AS , 33% mengalami GERD Swedia ,12% mengalami heartburn Singapura ( 1998) 1.6 % ,Taiwan 6% Indonesia ( ?), M.Djamil GERD 66.4%, BRG 24.5%

Definitions Heartburn: Esophagitis : Burning retrosternal pain radiating upward due to exposure of the oesophagus to acid Esophagitis : Endoscopically demonstrated damage to the oesophageal mucosa Gastro-esophageal reflux disease (GERD): Pathological reflux ranges from simple to erosive to Barrett’s Non-erosive reflux disease (NERD): Reflux disease in which erosion does not occur The primary symptom of acid-related diseases of the oesophagus is heartburn. The pain of heartburn can be severe and frightening for the patient. It can mimic the pain of a heart attack, so it is important to take seriously any symptoms with sudden onset. On examination, many patients with heartburn have oesophagitis – inflammation of the oesophagus that can be seen on endoscopy. Gastro-oesophageal reflux disease (GORD) is the pathological mechanism by which acid arrives in the oesophagus to cause inflammation/erosion of the oesophageal mucosa. Many patients with GORD do not have evidence of oesophagitis and are classified as having non-erosive or negative-endoscopy reflux disease (NERD). Barrett’s oesophagus is a pre-cancerous lesion. Throughout this presentation, GORD is equivalent to gastro-esophageal reflux disease, GERD. Talley et al., BMJ 2001; 323: 1294–7. de Caestecker, BMJ 2001; 323: 736–9. Nathoo, Int J Clin Pract 2001; 55: 465–9. Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.

Pathophysiology of GERD The pathophysiology of reflux disease is multifactorial Gastroduodenal factors : - Acid and pepsin - Duodenal agents - Gastric emptying - Helicobacter pylori ? Gastroesophageal junction factors : - Transient lower esophageal sphincter relaxation - Hypotensive lower esophageal sphincters - Hiatal hernia Esophageal factors : - Esophageal clearance Genetic factors Fass R. GERD .2004

Pathophysiology of GERD gastric emptying (fat) salivary HCO3 Impaired mucosal defence oesophageal clearance of acid (lying flat, alcohol, coffee) Impaired LOS (smoking, fat, alcohol) – transient LOS relaxations – basal tone Hiatus hernia acid output (smoking, coffee) There are several possible mechanisms that can account for increased gastro-oesophageal reflux. These include: reduced salivary bicarbonate impairs neutralisation of gastric acid (may be caused by reduced secretion or impaired peristalsis and reduced saliva transport) impaired mucosal defence/acid clearance in the oesophagus (normal peristaltic activity in the oesophagus causes acid to be cleared back into the stomach – lying flat and agents such as alcohol and caffeine impair this mechanism increased reflux of acid from the stomach due to impaired pressure at the lower oesophageal sphincter, to increased back pressure from the stomach or to delayed gastric emptying (which allows acid to stay longer in the stomach and hence have more opportunity to reflux into the oesophagus). Many lifestyle factors, such as smoking, alcohol intake, fat intake and obesity can cause GORD. LOS = lower oesophageal sphincter. H+ Pepsin Bile and pancreatic enzymes intragastric pressure (obesity, lying flat) bile reflux gastric emptying (fat) de Caestecker, BMJ 2001; 323:736–9. Johanson, Am J Med 2000; 108(Suppl 4A): S99–103.

PATOGENESIS GERD(1): Refluks isi lambung kedalam esofagus merupakan hal yang normal. Patologis bila terjadi gangguan bersihan lumen esofagus terhadap isi lambung Proses berlangsung lama dan berulang

PATOGENESIS GERD(2): Terjadi penurunan resistensi jaringan mukosa esophagus Pola hidup tertentu, pola makan, merokok, berat badan Infeksi H pylori? Penurunan tonus sfingter esofagus bawah ?

GERD dan motilitas : Kelainan motorik/motilitas esofagus akan berakibat gangguan terhadap bersihan lumen dari refluksat. Lamanya kontak refluksat dengan mukosa esofagus disertai dengan frekuensi refluks akan dapat berakibat terjadinya GERD Tonus LES juga dapat berakibat lebih beratnya kelainan

GERD & Infeksi H pylori: Peranan infeksi H.pylori dalam patogenesis GERD relatif kecil dan kurang didukung oleh data yang ada. Ada hubungan terbalik antara infeksi H.pylori dengan strain yang virulens (Cag A Positif) dengan kejadian esofagitis, Barrett’s esophagus & adenokarsinoma esofagus

Pola hidup & GERD: Peranan alkohol, diet serta faktor psikis tidak signifikan dalam patogenesis GERD. Beberapa studi observasional telah menunjukkan pengaruh merokok dan berat badan lebih sebagai faktor risiko terjadinya GERD

DIAGNOSIS GERD: Standar baku diagnosis GERD adalah endoskopi saluran cerna bagian atas (SCBA) dengan ditemukannya mucosal break di esophagus Anamnesis yang cermat merupakan alat utama untuk menegakkan diagnosis GERD

Diagnosis NERD: Gejala klinik tipikal GERD Tidak ditemukannya mucosal break pada pemeriksaan endoskopi SCBA Pemeriksaan pH esofagus dengan hasil positif Terapi empiris yang banyak dikenal dengan Proton Pump Inhibitor (PPI) Test dengan hasil positif.

Diagnosis GERD  Endoscopi sal. cerna bgn atas  kerusakan jaringan.6 NERD  Tidak ada kerusakan jaringan (endoskopi) Pemeriksaan pH esophagus  hasil (+) Terapi empiris (PPI test)  hasil (+) Anamnesis.7 dan pemeriksan penunjang lainnya

Pemeriksaan penunjang GERD: Endoskopi Pemeriksaan histopatologi Pemeriksaan pH metri 24 jam Penunjang diagnostik lain: Esofagografi dengan barium, Manometri esofagus

Los Angeles classification system for esophagitis Grade A Grade B One or more mucosal breaks, no longer than 5 mm, that do not extend between the tops of two mucosal folds One or more mucosal breaks, more than 5 mm long, that do not extend between the tops of two mucosal folds Grade C Grade D The Los Angeles classification system can be used to describe varying severities of reflux oesophagitis. The Savary-Miller classification can also be used to classify oesophagitis (see next slide) and is more commonly used in Europe. One or more mucosal breaks, that are continuous between the tops of two or more mucosal folds, but which involve less than 75% of the circumference One or more mucosal breaks, that involve at least 75% of the oesophageal circumference Lundell et al., Gut 1999; 45: 172–80.

Savary-Miller classification of esophagitis Grade I One or several erosions in one mucosal fold Grade II Several erosions in several mucosal folds, the erosions can merge Grade III Erosions surrounding the oesophageal circumference Grade IV Ulcer(s), strictures, shortening of the oesophagus Grade V Barrett’s epithelium The Savary-Miller classification system for oesophagitis is most often used in Europe. Savary & Miller. The Esophagus. In: Handbook & Atlas of Endoscopy. Solothurn, Switzerland: Verlag Gassman AG, 1978: 119–205.

Grade I esophagitis Savary-Miller classification One or several erosions in one mucosal fold Reflux oesophagitis grade I. The most common cause of oesophagitis is gastro-oesophageal reflux. Of people with GORD, roughly 40% will develop oesophagitis (histologically proven), while 60% will have non-erosive oesophagitis. The most common symptoms of GORD are heartburn and regurgitation. The major complications are Barrett's epithelium, stricture, ulceration and bleeding. Reproduced with permission. Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18. Nathoo, Int J Clin Pract 2001; 55: 465–9. www.gastrolab.net

Grade II esophagitis Savary-Miller classification Several erosions in several mucosal folds, the erosions can merge Reflux oesophagitis grade II. Numerous, confluent, erosive, partly fibrin-covered lesions are visible. The observation that lesions do not cover the whole oesophageal circumference distinguishes this severity of oesophagitis as grade II rather than grade III. Reproduced with permission. www.gastrolab.net

Grade III esophagitis Savary-Miller classification Erosions surrounding the oesophageal circumference Reflux oesophagitis grade III. Erosive, fibrin-covered lesions affect the whole oesophageal circumference. Reproduced with permission. Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm

Savary-Miller classification Ulcer(s), shortening of the oesophagus Grade IV esophagitis Savary-Miller classification Ulcer(s), shortening of the oesophagus Reflux oesophagitis grade IV. Severe, haematin covered, ulcerous lesions are observed. These lesions cause a scarred shortening of the oesophagus (brachyoesophagus). Other cases show a singular ulcer. Reproduced with permission. Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm

Savary-Miller classification Moderate Barrett’s oesophagus Grade V esophagitis Savary-Miller classification Moderate Barrett’s oesophagus Grade V oesophagitis. Barrett’s mucosa is a metaplastic columnar epithelium that has replaced the native squamous cells at the oesophagocardiac junction. It is thought to provide greater resistance to gastro-oesophageal reflux, which in turn is likely to be the causal agent. The picture shows dark red, finger-like epithelial islands among areas of normal, non-inflamed, whitish, squamous epithelium. Only 15% of patients present with GORD-type symptoms. There is no correlation between the severity of symptoms and the severity grade of the endoscopic findings. Reproduced with permission. Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm

Savary-Miller classification Stricture Grade IV esophagitis Savary-Miller classification Stricture Grade IV oesophagitis. The oesophageal junction viewed from the distal oesophagus. The opening is not obviously narrowed, but when the scope touched the mucosa, the normal reflex opening did not occur, indicating stricture. Strictures may be peptic, caustic, post-radiation, inflammatory (non-peptic) including infectious and congenital. Peptic irritation is a major cause of oesophageal stricture through exposure of the oesophageal epithelium to the caustic effect of gastric acid. Stricture follows fibrous repair and is more likely to occur when significant necrosis or repeated episodes of oesophagitis have occurred. Stricture occurs most commonly in the lower third of the oesophagus, often near the gastro-oesophageal junction consistent with its origin in GORD. Dysphagia is the primary symptom of stricture with a gradual increase in difficulty of swallowing. Treatment is establishment of an adequate lumen by progressive dilatation of the stricture. Recurrent dilatation is often necessary. Treatment of the primary cause of oesophagitis should also be undertaken. Reproduced with permission. Nadel, UCHC.

Savary-Miller classification Moderate Barrett’s oesophagus Grade V esophagitis Savary-Miller classification Moderate Barrett’s oesophagus Grade V oesophagitis Methylene blue staining of a Barrett’s oesophagus. The normal squamous epithelium is stained only weakly, whereas the columnar Barrett’s epithelium takes up more dye. Reproduced with permission. Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm

Savary-Miller classification Severe Barrett’s oesophagus Grade V esophagitis Savary-Miller classification Severe Barrett’s oesophagus Grade V oesophagitis. In this severe case, all of the squamous epithelium of the lower oesophagus has been replaced by metaplastic Barrett’s epithelium (columnar epithelium). Reproduced with permission. Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm

Adenocarcinoma of the esophagus Adenocarcinoma of the gastro-oesophageal junction. The oesophageal mucosa to the left is labelled ‘E’. The gastric mucosa to the right is labelled ‘G’. The arrows point to the heaped up edge of the ulcerated lesion which is the carcinoma (located in the centre of the image). Most cases of oesophageal adenocarcinoma arise in the lower third of the oesophagus in the setting of pre-existent Barrett's oesophagus secondary to reflux oesophagitis. Dysphagia and weight loss are the two most common symptoms. Symptoms of pre-existing reflux are present in less than 50% of patients. Five-year survival is dismal at less than 15%. Primary therapy is surgery or chemotherapy with radiation therapy, but chemotherapy and radiation therapy are less effective in adenocarcinoma than in squamous cancer. Reproduced with permission. Nadel/Saint Francis Hospital. In: Gastrointestinal Pathology. Fenoglio-Preiser, New York: Raven Press, 1989: 96–100.

Alarm features for GERD Odynophagia Dysphagia Bleeding Alarm features Alarm features for GORD include: Dysphagia – difficulty swallowing Odynophagia – pain on swallowing Bleeding, which may present as melaena or haematemesis or result in anaemia. Weight loss can also include anorexia. The presence of one or more of these symptoms might indicate: underlying cardiac disease that is presenting as heartburn blockage of the oesophagus, possibly due to stricture or adenocarcinoma of the oesophagus. Vomiting Weight loss Nathoo, Int J Clin Pract 2001; 55: 465–9.

Tanpa gejala alarm kambuh ALGORITME TATA LAKSANA GERD PADA PELAYANAN KESEHATAN LINI PERTAMA GEJALA KHAS GERD Gejala alarm Umur > 40 th Tanpa gejala alarm Terapi empirik Tes PPI Respon menetap Endoskopi Respon baik Terapi min-4 minggu kambuh Konsensus Gerd ,2004 On demand therapy

Differential diagnosis of GERD Hiatus hernia Esophageal stricture Esophageal cancer Chest pain of cardiac origin Functional dyspepsia Patients presenting with symptoms of GORD may have a range of underlying conditions, so it is important to take a careful history, including the duration, location and severity of symptoms. If a simple trial of acid suppression is not successful in treating the symptoms, endoscopy will probably be required to establish a firm diagnosis. Nathoo, Int J Clin Pract 2001; 55: 465–9.

GERD treatment options Lifestyle modifications Antacids and alginates PPIs Approaches H2RAs For patients with typical GORD there are a number of long-term treatment approaches. In most patients the disease can be managed by lifestyle modifications and through the choice of appropriate antisecretory drug treatment (e.g. a PPI). Surgery is a last resort in GORD. Prokinetic motility agents Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.

Lifestyle modifications for the management of GERD Reduce weight Elevate head of bed Stop smoking Modifications Avoid reflux-promoting agents (e.g. alcohol, coffee, some foods) (not evidence based) As in all fields of medicine, lifestyle modifications are effective in the short term, but in the long term they require the patient to be highly motivated. Changing diet, stopping smoking and losing weight are all difficult for patients to achieve long term. Often patients will require counselling support and the use of antisecretory agents to remove symptoms while the lifestyle changes take effect. Eat small meals, no late meals, reduce fat

PRINSIP TERAPI PENGENDALIAN pH asam lambung enzim pepsin bekerja pada pH ideal = 2-2.5 pada pH > 4 aktivitas pepsin menurun drastis Enzim pepsin bekerja mencerna dinding protein lambung

PENGOBATAN GERD: Menghilangkan gejala / keluhan Menyembuhkan lesi esofagus Mencegah kekambuhan Memperbaiki kualitas hidup Mencegah timbulnya komplikasi

KONSENSUS NASIONAL PENATALAKSANAAN PENYAKIT REFLUKS GASTROESOFAGEAL (GASTROESOPHAGEAL REFLUX DISEASE/GERD) INDONESIA 2004

Terapi GERD dengan PPI: Pengobatan awal dengan PPI dengan dosis ganda selama 8 minggu dengan dosis ganda. Selanjutnya tergantung perbaikan klinik dan endoskopi, dalam bentuk terapi on demand atau maintenance therapy sampai 6 bulan PPI dosis ganda selama 8 minggu dapat memberikan healing rate lebih dari 80%

Penatalaksanaan GERD TERAPI AWAL / INITIAL Esofagitis ringan TERDUGA KASUS REFLUKS Gejala Alarm/ Usia > 40 tahun Keluhan berulang UNINVESTIGATED INVESTIGATED PENGOBATAN EMPIRIK 2 minggu ( PPI test ? ) TERAPI AWAL / INITIAL PPI test : 1-2 minggu Dosis ganda (Sensitivitas 68-80%) Esofagitis sedang & berat Gejala berulang Esofagitis ringan NERD TERAPI “BILA PERLU” TERAPI PEMELIHARAAN Indonesia GERD study group

ALGORITME TATA LAKSANA GERD PADA PELAYANAN KESEHATAN LINI PERTAMA Gejala khas GERD Heartburn Regurgitasi Gejala Alarm/ Umur > 40 tahun Tanpa gejala Alarm Respon menetap Respon baik GERD+ Endoskopi Terapi minimal 4 minggu kekambuhan On demand therapy Indonesia GERD study group

Algorithm Pengobatan Yang dianjurkan untuk Pasien GERD PPI Pengobatan awal 4-8 minggu Severe EE , Serangan Yang sering Atau Respons PPI lambat Uninvestigated, Mild EE Atau NERD PPI On-Demand PPI Maintenance Indonesia GERD study group

Pertimbangan terapi GERD PPI :  Cepat dalam menghilangkan keseluruhan gejala  Cepat dalam penyembuhan  Pendekatan Step-down  Yang dipilih : Cepat dalam penghambatan asam Konsisten mengontrol asam pada pH>4 Sedikit interaksi dengan obat lain Sedikit efek pada cytochrome P450  Omeprazole ? Rabeprazole ? Lanzoprazole ? Esomeprazole ? Pantoprazole ?

KESIMPULAN Terdapat peningkatan prevalensi GERD Patofisiolgi multifaktor akibat peningkat an asam lambung, gangguan motilitas,dll Keluhan berupa heartburn , noncardiac chest-pain Terapi life style

MINAL AIDIN WAL FAIDZIN MAAF LAHIR DAN BATHIN TERIMA KASIH