What is acid reflux?

Factors related to the Stomach:
Stomach factors (particularly stomach content's volume and certain aggressive factors found in the refluxate) are potentially important in the production of reflux esophagitis. Stomach volume is determined by the basal acid secretion rate, concomitant H pylori infection, duodenogastric reflux, and the rate of stomach emptying. Increased stomach volume not only provides more stomach contents available for reflux, but also increases the rate of transient LESRs.

Stomach Acid Secretion

The primary importance of stomach acid is indisputable in the production of reflux esophagitis, but its mechanism may involve activation of pepsin rather than direct damage from acid alone. In animal studies, acid causes minimal injury at a pH of less than 3.0, primarily by protein denaturation. However, the combination of acid and even small amounts of pepsin disrupts the mucosal barrier resulting in increased H + permeability, histological changes, and gross hemorrhage. Complementing the animal studies, a series of clinical reports showed that patients with various grades of esophagitis, including Barrett esophagus, have increased frequency and duration of esophageal exposure to Stomach refluxate of pH lower than 4. Conversely, perfusing the esophagus of animals with a pepsin solution of pH 7.5 produces minimal mucosal disruption or changes in permeability. These observations are the cornerstone of acid suppressive therapy in the treatment of GERD.

Some studies have suggested that patients with reflux, especially those responding poorly to conventional antisecretory therapy, may have higher rates of acid secretion than controls. However, most evidence finds no abnormality of Stomach acid secretion in patients with GERD. Factors that reduce Stomach acid secretion naturally, for example, concomitant infection with H pylori, especially if it is the cagA + virulent strain, may protect from the development of severe esophagitis and Barrett esophagus. H pylori infection, particularly infection with this virulent strain, is a biologic antisecretory agent that lowers Stomach acidity. It produces severe corpus gastritis and accelerates the progression to multifocal atrophic gastritis and intestinal metaplasia, with concomitant lower acid output. In addition, the bacteria produce ammonia that acts as a powerful neutralizing agent at elevated pH conditions. The corpus mucosa returns to normal when the H pylori infection is cured, increasing acid secretion and possibly contributing to the reports of esophagitis after successful treatment of H pylori infection. The consequences of long-term normalization of parietal cell function and return to higher intragastric acidity is unknown, but they could promote the development of more severe GERD, Barrett esophagus, and adenocarcinoma in Western populations.

Duodenogastric Reflux

Bile acids have been implicated in the development of esophagitis, especially in the presence of increased duodenogastric reflux. Studies in animals demonstrate that conjugated bile acids produce their greatest injury in the presence of acid and pepsin, whereas trypsin, deconjugated bile salts, are more damaging in the absence of acid. Several surgical reports have suggested that duodenogastric reflux into the esophagus is frequent and may predispose to complications of GERD. However, accurate measurement of duodenogastric reflux is difficult. Duodenogastric reflux may be indirectly estimated by ambulatory pH studies using an esophageal pH of less than 7 to indicate alkaline reflux. However, the reliability of this indirect marker is now questioned by newer techniques, which either spectrophotometrically measure bilirubin, the most common pigment in bile, or measure esophageal impedance of the flow of liquids and gases independent of pH. These studies show that acid reflux and bile reflux increase together across the spectrum of GERD, making it nearly impossible to incriminate one agent over the other in the development of esophagitis. In addition, aggressive acid suppression with proton pump inhibitors (PPIs) decreases both acid and duodenogastric reflux probably by decreasing the volume of Stomach contents available to reflux into the esophagus. Finally, the absence of membrane microvesiculation and intracellular bile deposits in human esophageal biopsies, two distinctive morphologic features of experimental acid-bile salt injury, also argue against an important role for bile salts in GERD.

Delayed Stomach Emptying

The importance of delayed Stomach emptying in the pathogenesis of GERD is controversial. Early studies observed a delay in the Stomach emptying of solids in up to 50% of patients with reflux. More recent studies found only a 6% to 38% rate of delayed Stomach emptying, regardless of the severity of the esophagitis. Nevertheless, delayed Stomach emptying may be a major factor contributing to GERD in some groups, such as diabetic patients with autonomic peripheral neuropathy.

Associated Conditions

Certain medical and surgical conditions can predispose a person to GERD. The most common is pregnancy; 30% to 50% of pregnant women complain of heartburn, especially in the first trimester. Pregnancy increases the risk for reflux by the relaxing effects of circulating estrogens and progesterones on LES pressure. Although symptoms may be severe, esophagitis is uncommon, and this type of “situational” GERD is cured with childbirth.

Up to 90% of patients with scleroderma have GERD as the result of smooth muscle fibrosis causing low LES pressure and weak or absent peristalsis. Severe disease is common; up to 70% of patients have esophagitis, many have peptic strictures, and Barrett esophagus and carcinoma of the esophagus have been reported.

Unlike the previous two conditions that are characterized by LES dysfunction, hypersecretion of acid and increased Stomach volume are the major factors causing GERD in patients with the Zollinger-Ellison syndrome. In these patients, the esophagitis and complications may be more difficult to treat than the ulcer disease. After Heller myotomy, 10% to 20% of patients may develop GERD. Finally, prolonged nasogastric intubation may contribute to the development of reflux esophagitis, in part because acid tracks orad along the tube and because the tube mechanically interferes with LES barrier function.