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NASRUL ZUBIR

Gastroesophageal Reflux Disease( GERD)

Dr. SAPTINO MIRO, SpPD

BAGIAN ILMU PENYAKIT DALAM FK-UNAND/RS.M.DJAMILPADANG1

2Pendahuluan 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

3Epidemiologi Di AS , 33% mengalami GERD Swedia ,12% mengalami heartburn Singapura ( 1998) 1.6 % ,Taiwan 6% Indonesia ( ?), M.Djamil GERD 66.4%, BRG 24.5%4Talley et al., BMJ 2001; 323: 12947.de Caestecker, BMJ 2001; 323: 7369.Nathoo, Int J Clin Pract 2001; 55: 4659.Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S1318.Heartburn: Burning retrosternal pain radiating upward due to exposure of the oesophagus to acidEsophagitis :Endoscopically demonstrated damage to the oesophageal mucosaGastro-esophageal reflux disease (GERD):Pathological reflux ranges from simple to erosive to BarrettsNon-erosive reflux disease (NERD):Reflux disease in which erosion does not occurDefinitions5The 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).Barretts oesophagus is a pre-cancerous lesion.

Throughout this presentation, GORD is equivalent to gastro-esophageal reflux disease, GERD.

Pathophysiology of GERDThe 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 factorsFass R. GERD .20046

Impaired mucosal defencede Caestecker, BMJ 2001; 323:7369.Johanson, Am J Med 2000; 108(Suppl 4A): S99103.salivary HCO3Hiatus herniaImpaired LOS (smoking, fat, alcohol)

transient LOS relaxations

basal toneH+ PepsinBile and pancreatic enzymes oesophageal clearance of acid (lying flat, alcohol, coffee) acid output (smoking, coffee) intragastric pressure (obesity, lying flat)bile refluxgastric emptying (fat)Pathophysiology of GERD7There 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 mechanismincreased 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.

8PATOGENESIS GERD(1):Refluks isi lambung kedalam esofagus merupakan hal yang normal.Patologis bila terjadi gangguan bersihan lumen esofagus terhadap isi lambungProses berlangsung lama dan berulang9PATOGENESIS GERD(2):Terjadi penurunan resistensi jaringan mukosa esophagusPola hidup tertentu, pola makan, merokok, berat badanInfeksi H pylori?Penurunan tonus sfingter esofagus bawah ?

10GERD 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 GERDTonus LES juga dapat berakibat lebih beratnya kelainan 11GERD & 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, Barretts esophagus & adenokarsinoma esofagus12Pola 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

13DIAGNOSIS 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 14Diagnosis NERD:Gejala klinik tipikal GERDTidak ditemukannya mucosal break pada pemeriksaan endoskopi SCBAPemeriksaan pH esofagus dengan hasil positifTerapi empiris yang banyak dikenal dengan Proton Pump Inhibitor (PPI) Test dengan hasil positif.15DiagnosisGERD Endoscopi sal. cerna bgn atas kerusakan jaringan.6NERD Tidak ada kerusakan jaringan (endoskopi)Pemeriksaan pH esophagus hasil (+)Terapi empiris (PPI test) hasil (+)Anamnesis.7 dan pemeriksan penunjang lainnya16Pemeriksaan penunjang GERD:EndoskopiPemeriksaan histopatologiPemeriksaan pH metri 24 jamPenunjang diagnostik lain: Esofagografi dengan barium, Manometri esofagus17One or more mucosal breaks, no longer than 5 mm, that do not extend between the tops of two mucosal foldsGrade AOne or more mucosal breaks, more than 5 mm long, that do not extend between the tops of two mucosal foldsGrade BOne or more mucosal breaks, that are continuous between the tops of two or more mucosal folds, but which involve less than 75% of the circumferenceGrade COne or more mucosal breaks, that involve at least 75% ofthe oesophageal circumferenceGrade DLundell et al., Gut 1999; 45: 17280.Los Angeles classification system for esophagitis18The 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.

Savary & Miller. The Esophagus. In: Handbook & Atlas of Endoscopy. Solothurn, Switzerland: Verlag Gassman AG, 1978: 119205.

Savary-Miller classification of esophagitisGrade IOne or several erosions in one mucosal fold

Grade IISeveral erosions in several mucosal folds, the erosions can merge

Grade IIIErosions surrounding the oesophageal circumference

Grade IVUlcer(s), strictures, shortening of the oesophagus

Grade VBarretts epithelium19The Savary-Miller classification system for oesophagitis is most often used in Europe.

Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S1318.Nathoo, Int J Clin Pract 2001; 55: 4659.www.gastrolab.netSavary-Miller classification

One or several erosions in one mucosal foldGrade I esophagitis20Reflux 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.www.gastrolab.net

Savary-Miller classification

Several erosions in several mucosal folds, the erosions can mergeGrade II esophagitis21Reflux 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.

Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htmSavary-Miller classification

Erosions surrounding the oesophageal circumferenceGrade III esophagitis22Reflux oesophagitis grade III.Erosive, fibrin-covered lesions affect the whole oesophageal circumference.



Ulcer(s), shortening of the oesophagusGrade IV esophagitis23Reflux 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.



Moderate Barretts oesophagusGrade V esophagitis24Grade V oesophagitis.Barretts 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.


Nadel, UCHC.Savary-Miller classification

Stricture

Grade IV esophagitis25Grade 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.



Moderate Barretts oesophagusGrade V esophagitis26Grade V oesophagitisMethylene blue staining of a Barretts oesophagus. The normal squamous epithelium is stained only weakly, whereas the columnar Barretts epithelium takes up more dye.



Severe Barretts oesophagusGrade V esophagitis27Grade V oesophagitis.In this severe case, all of the squamous epithelium of the lower oesophagus has been replaced by metaplastic Barretts epithelium (columnar epithelium).


Nadel/Saint Francis Hospital. In: Gastrointestinal Pathology. Fenoglio-Preiser, New York: Raven Press, 1989: 96100.

Adenocarcinoma of the esophagus 28Adenocarcinoma 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.


OdynophagiaDysphagiaVomitingBleedingWeight lossAlarm featuresNathoo, Int J Clin Pract 2001; 55: 4659.Alarm features for GERD29Alarm features for GORD include: Dysphagia difficulty swallowingOdynophagia pain on swallowingBleeding, 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 heartburnblockage of the oesophagus, possibly due to stricture or adenocarcinoma of the oesophagus.

ALGORITME TATA LAKSANA GERD PADA PELAYANAN KESEHATAN LINI PERTAMAGEJALA KHAS GERDGejala alarmUmur > 40 thTanpa gejala alarmTerapi empirikTes PPIRespon menetapRespon baikTerapi min-4 mingguOn demand therapykambuhEndoskopiKonsensus Gerd ,200430Hiatus herniaEsophageal strictureEsophageal cancerChest pain of cardiac origin Functional dyspepsiaNathoo, Int J Clin Pract 2001; 55: 4659.Differential diagnosis of GERD31Patients 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.

PPIsH2RAsLifestyle modificationsProkinetic motility agentsAntacids and alginatesHatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386406.ApproachesGERD treatment options32For 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.

Reduce weightStop smokingAvoid reflux-promoting agents (e.g. alcohol, coffee, some foods) (not evidence based)Elevate headof bedModificationsEat small meals,no late meals, reduce fatLifestyle modifications for the management of GERD33As 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. 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 lambung34PENGOBATAN GERD:Menghilangkan gejala / keluhanMenyembuhkan lesi esofagusMencegah kekambuhanMemperbaiki kualitas hidupMencegah timbulnya komplikasi 35

KONSENSUS NASIONAL PENATALAKSANAAN PENYAKIT REFLUKS GASTROESOFAGEAL (GASTROESOPHAGEAL REFLUX DISEASE/GERD) INDONESIA 200436Terapi 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 bulanPPI dosis ganda selama 8 minggu dapat memberikan healing rate lebih dari 80%

37

Penatalaksanaan GERDTERDUGA KASUS REFLUKSUNINVESTIGATEDINVESTIGATEDPENGOBATAN EMPIRIK 2 minggu ( PPI test ? ) TERAPI AWAL / INITIAL Esofagitis ringan NERDEsofagitis sedang & berat Gejala berulang TERAPI PEMELIHARAAN TERAPI BILA PERLUGejala Alarm/Usia > 40 tahunKeluhan berulangPPI test : 1-2 minggu Dosis ganda (Sensitivitas 68-80%)

Indonesia GERD study group38Gejala khas GERDHeartburnRegurgitasiGejala Alarm/Umur > 40 tahunTanpa gejala AlarmRespon menetapRespon baikTerapi minimal 4 mingguOn demand therapykekambuhanEndoskopiALGORITME TATA LAKSANA GERD PADA PELAYANAN KESEHATAN LINI PERTAMAGERD+Indonesia GERD study group39PPI Pengobatan awal4-8 mingguAlgorithm Pengobatan Yang dianjurkan untuk Pasien GERDPPIOn-DemandPPIMaintenanceSevere EE , Serangan Yang seringAtau Respons PPI lambatUninvestigated,Mild EE Atau NERDIndonesia GERD study group40PPI :Cepat dalam menghilangkan keseluruhan gejalaCepat 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 ?Pertimbangan terapi GERD41KESIMPULANTerdapat peningkatan prevalensi GERDPatofisiolgi multifaktor akibat peningkat an asam lambung, gangguan motilitas,dllKeluhan berupa heartburn , noncardiac chest-painTerapi life style42

TERIMA KASIH43

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