What factors contribute to alkaline reflux and why?
S.J.M. Kraemer, HJ. Stein, H. Feussner, J.R. Siewert (Munich)
Reflux of "alkaline" duodenal juice into the stomach is a naturally occurring sporadic event. However, the explanations for this phenomenon are still not satisfactory. Nonetheless, excessive duodenogastric reflux (DGR) is accused of being associated with a variety of symptoms, such as:
- epigastric pain (89%); and
- bilious vomiting (94%) .
DGR with intragastric bile collections is heavily disputed as a cause for:
- gastric ulcerations;
- development of antral gastritis;
- atrophic gastritis;
- gastric carcinoma; and
- "alkaline" gastroesophageal reflux (GER) [1-3]. The main components of the alkaline duodenal juice are:
- bile salts;
- activated pancreatic; and
- other intestinal enzymes, which ultimately lead to gastric mucosal barrier damage. Bile acids, for example, are capable of disrupting the gastric mucosa, allowing back diffusion of hydrogen ions into the stomach wall, initiating one of the pathways to gastritis and ulceration [4,5]. It has been demonstrated that most enzymes are highly
effective - and more harmful - in an almost neutral environment and that the pH does not correlate well with their cell toxicity or the patients pain.
Physiologically, the antropyloroduodenal segment (APD) is an antireflux barrier. This "biosphincter" nevertheless allows, as an intermittent sporadic natural event, "physiologic" DGR in fasting and fed states, primarily occurring postprandial and during the early morning hours (in the supine position). The physiologic process presumably turns pathologic when the exposure time of the duodenal juice to the gastric mucosa is extended as a result of dysmotility of the APD and an anatomically intact, but increasingly incompetent pylorus. As a result, the refluxed duodenal juice has a prolonged contact time with the gastric mucosa, caused by:
- frequent reflux episodes;
- insufficient gastric clearance; or
- diminished gastric secretion .
Secondary and probably more frequent factors for intractable symptoms of DGR due to inadequate biliary drainage, like pain and bilious vomiting, are postoperative situations after:
- vagotomies (?);
- distal gastric resections with Billroth I or II reconstructions; and
- total gastrectomies with the resection of the lower esophageal sphincter (LES) [7-13].
Excessive DGR may also occur in patients with previous biliary surgery or cholecystectomy [14,15], probably due to an increased and steady flow of bile into the duodenum. Yet the relation of cause and effect is still unclear. In the discussion are:
- the absence of a bile reservoir;
- pooling of bile in the duodenum;
- an incriminated duodenal motility;
- alteration of the normal anatomy;
- changes in neurohormonal reactions on gastrin, cholecystokinin (CCK) and others. In patients with general systemic disorders and intestinal motility disorders, DGR is not an uncommon phenomenon (e.g., in scleroderma or diabetes) .
Finally, DGR may occur in patients with small or large bowel obstructions and in those patients suffering from intra-abdominal benign or, more commonly, malignant tumors or tumor recurrences. Tumor growth either leads to a mechanical obstruction of the gut, which ultimately results in DGR and finally GER, or the intra-abdominal pressure increases with the increasing volume of the tumor, thus leading to DGR or alkaline or mixed gastroesophageal reflux disease (GERD). A similar cause can be found in women with both forms of temporary reflux disease during pregnancy.
The discussion about the phenomenon of "alkaline DGR" after previous gastric or biliary surgery and also the dispute concerning "alkaline" esophagitis, which frequently seems to be one of the sequelae of prolonged excessive DGR, are still very controversial.
Acid or biliary GERD may lead to such complications as heartburn, esophagitis, ulceration, dysphagia, stricture, upper Gl-bleeding, Barrett's esophagus and cancer.
GERD is the most common disorder of the upper gastrointestinal tract in humans. It accounts for significant morbidity, which may be as high as 50% in the affected patient population [17,18]. A large body of experimental and clinical evidence demonstrates that GERD results from a partial or complete loss of the gastroesophageal antireflux barrier (GEARB):
- loss of the gastroesophageal valve mechanism (GEV);
- a nonfunctioning lower esophageal sphincter (LES);
- a compromised esophageal clearance function; and the
- exposure of the esophageal mucosa to refluxed gastric contents;
have been identified as predisposing factors to the development of these complications [19-21].
As part of the standard acid reflux testing (SART), acid GER is measured routinely by pH-testing with an H+ ion sensitive antimony or glass probe. However, refluxed gastric juice may contain alkaline duodenal contents, lipophilic bile salts, lysolecithin and activated pancreatic and other intestinal enzymes, of which all also promote esophageal mucosal injury in patients with GERD [20,22,23]. These combined forms of acidic and alkaline reflux are frequently found in patients with severe intractable GERD .
These cases of alkaline or mixed GER are extremely hard to assess so far, since pH-testing has its limitations in the alkaline environment . It has often been discussed that the "alkaline" reading on the pH-probe is due to saliva coming down into the stomach. If bile salts and enzymes are actually identified, one can say that there is alkaline or mixed reflux present.
The problem of measuring alkaline reflux is not a problem of measuring (OH-) groups, but it is a problem of a direct analysis of the quality and quantity of the components of the refluxed alkaline or mixed alkaline/acid duodenogastric juice. With new methods like the ambulatory 24-h reflux aspiration test, in combination with the high performance liquid column chromatography (HPLC), new standards are being developed [7,16].
"Alkaline" reflux - per se - is not the villain. It is rather the excessive DGR and GERD with its bile salts, activated pancreatic and other intestinal enzymes, which can exist in an acid environment and are more harmful and which seem to be responsible for a number of symptoms and histological changes in the foregut.
Whereas a dysfunctional or destroyed antroduodenal segment is an absolute precondition for DGR, alkaline or mixed GER is due to a combination of the presence of excessive DGR and a partial or complete loss of the GEARB. If GER is stopped by creating an adequate GEARB with a good antireflux repair, then alkaline GER is corrected as well.
A prevention or reduction of postoperative DGR can best be achieved by an adequate biliary drainage operation, preferably - according to experience - a Roux en Y derivation procedure.
5. Pazzi P, Scalia S, Stabellini G, Trevisani L, Alvisi V, Guarneri M. Bile reflux gastritis in patients without prior gastric surgery: Therapeutic effects of ursodeoxycholic acid. Curr Ther Res 1989;45(3):476-487.
7. Feussner H, Weiser HF, Liebermann-Meffert D, Siewert JR. Intestino-ösophagealer reflux nach gastrektomie. Wirkungs-mechanismus und effektivität der oesophagojejunoplicatio. Chirurg 1988;59:665-669.
16. Feussner H. Oesophageal refluxkrankheit: Qualitative und quantitative refluatanalyse. Klinische Bedeutung des "Nicht-Sauren" Refluxes. Habilitationsschrift, Medizinische Fakultät, Technische Universität, München, 1992.
18. DeMeester TR, Stein HJ. Gastroesophageal reflux disease. In: Moody FG, Carey LC, Jones RC, Kelly KA, Nahrwold DL, Skinner DB (eds) Surgical Treatment of Digestive Disease, 2nd edn. Chicago: Year Book Medical Publishers, 1989; 65-108.
20. Stein HJ, Barlow AP, DeMeester TR, Hinder RA. Complications of gastroesophageal reflux disease: Role of the lower esophageal sphincter, esophageal acid/alkaline exposure and duodenogastric reflux Ann Surg 1992;216:35-43.
25. Mittal RK, Reuben A, Whitney JO, McCallum RW. Do bile acids reflux into the esophagus? A study in normal subjects and patients with gastroesophageal reflux disease. Gastroenterology 1987;92(2):371-375.