Duodenogastroesophageal reflux and its effect on extraesophageal tissues: a review

Ear, Nose & Throat Journal, April, 2008 by Joel H. Blumin, Albert L. Merati, Robert J. Toohill

Abstract

We conducted a literature review to identify elements of duodenogastroesophageal reflux (DGER)--namely pancreatic fluids, hydrochloric acid, pepsin, and bile--as to the effects each has when refluxed to the extraesophageal structures. Further, we wished to acquaint clinicians with the possibilities that, in addition to hydrochloric acid, the other components of DGER are likewise contributing to disease in the extraesophageal areas. Our review included studies that have indicated reflux of the above mentioned components of DGER to the pharynx, larynx, tracheobronchial tree, oral cavity, nasopharynx, nose and sinuses, eustachian tube, and middle ear. Findings demonstrate that injury to the upper aerodigestive tract can occur from a variety of substances secreted from the stomach and duodenum. Treatment for DGER is nonspecific. We conclude that patients with an incomplete response to acid suppression may have significant involvement of pepsin, bile, or both. Future studies are needed to clarify the importance of these elements and to suggest more precise treatments.

Introduction

Even though the extraesophageal manifestations of gastroesophageal reflux (GER) are well known to the modern otolaryngologist, the management of some patients with GER still remains elusive. Our armamentarium is primarily directed toward acid suppression; nonacidic reflux is not specifically addressed.

The digestive tract is a continuous valveless tube from the mouth to the anus. Peristalsis and sphincteric zones tend to keep foods and secretions moving in an anterograde direction; however, a variety of chemical and enzymatic agents can still move in a retrograde direction, thus producing "reflux." The upper aerodigestive tract is conjoined at the pharynx, and this refluxate has the potential to reach all subsites: the oral cavity and oropharynx; the sinonasal cavity, nasopharynx, and middle ear; and the larynx and tracheobronchial tree. Major constituents of enteric secretions are listed in the table.

Pancreatic juices consist of an alkaline solution of sodium and calcium bicarbonates and the digestive enzymes of lipase, trypsin, chymotrypsin, and amylase. The alkaline solution neutralizes the acidic, partially digested food from the stomach (chyme). Lipase is responsible for digestion of fats, trypsin and chymotrypsin are responsible for proteins, and amylase is active in carbohydrate digestion. These are secreted into the pancreatic duct, where they are combined with the secretion of the liver, namely bile. Bile principally consists of two bile salts, taurocholic acid and chenodeoxycholic acid, as well as bilirubin. Taurocholic acid is conjugated and is active in an acidic environment of pH 1.2 to 1.5 but is inactivated at a neutral pH. (1) Chenodeoxycholic acid is unconjugated and is active at a neutral pH but not at an acid pH of 2.0. (1) Bilirubin represents the end-product of hemoglobin breakdown and is nontoxic when secreted into the duodenum.

In response to a meal, the stomach secretes gastric juices that consist largely of HCl and pepsin. Pepsinogen is secreted by the chief cells of the stomach and is converted to pepsin in the acid medium. It is active in the digestion of proteins and peptides.

Reflux of acidic gastric contents to the esophagus and extraesophageal structures of the upper aerodigestive tract was demonstrated in Koufman's landmark 1991 study (2) and has been further substantiated over the past 2 decades by multiple clinical and basic scientific studies. (3-8) Recent research also has demonstrated ties between pepsin and inflammation of the laryngopharynx, (9-13) further bridging the reflux of gastric contents to the pathophysiology of aerodigestive tract mucosal injury. A few studies have specifically looked into the reflux of nonacidic duodenogastroesophageal reflux (DGER). The goal of this review article is to familiarize clinicians with those studies as reported in the literature.

Literature search

The U.S. National Library of Medicine's PubMed database was searched using keywords relating to DGER and the anatomic subsites of the upper aerodigestive tract. We limited our search to English language papers published from 1966 to the time of our search. Both clinical and basic scientific articles were reviewed.

Search results

Compared to the body of literature available on GER, there are few studies on the effects of DGER on the upper aerodigestive tract. Sixty-five articles were identified that discussed DGER alone, and 34 additional publications were identified that included the role of pepsin in extraesophageal inflammation. In all, 921 publications were identified that related to the effects of acid reflux on extraesophageal structures when articles about GER (16,099 articles) were excluded.

Duodenal secretions. Little research has been published regarding the effects of pancreatic fluids on the mucosa of the esophagus or extraesophageal structures. Trypsin has been shown to induce ultrastructural changes on rat buccal epithelium, (14) and on esophageal mucosa at alkaline and not acidic pFI, (15) yet in other studies trypsin has been shown not to induce inflammation in the larynx. (16,17) There does not seem to be an efficient assay to clinically evaluate patients for reflux of trypsin or pancreatic fluids. Sodium-ion--selective electrodes placed in the stomach have been used to detect pancreatic fluid, but this method has not been extensively used in an ambulatory clinical setting. (18)