Gastroesophageal Reflux

Pathophysiology

As mentioned, the primary mechanism for GERD is transient LES relaxations (TLESR). The result of these inappropriate LES relaxations is the presence of gastric refluxate in direct contact with the esophageal mucosa. Although initially felt to be purely acidic, recent research has indicated that up to 40% of refluxate is not acidic. Studies have shown that the occurrence of nonacid (pH > 7) and/or weakly acidic reflux (4 < pH < 7) varies between 45% and 90% in children and infants. Also, adult studies have implicated alkaline reflux as a causative factor in the development of Barrett esophageal metaplasia. The pathologic events that occur because of GERD are due to one or multiple failures of the normal physiologic barriers that help prevent gastric contents from entering the esophagus, that help limit injury to the esophagus as a result of gastric refluxate, or that help clear the refluxate that enters the esophagus ( Table 28.1 ).

In adults, the consequence of this refluxate in the esophagus is primarily limited to erosive esophagitis, esophageal stricture, and Barrett esophagitis. In children, its detrimental effects are much broader. Also, associated physiologic, anatomic, and developmental abnormalities coexist in children that make GERD and its consequences much more complex. Many children with GERD have significant neurologic impairment. These children can have increased spasticity with retching and related increased abdominal pressures. Poor swallowing mechanisms lead to gagging and choking, which add to this intermittent increase in abdominal pressure. Sometimes, a hiatal hernia develops ( Fig. 28.1 ), further predisposing to GERD. Congenital anomalies such as esophageal atresia (EA) with or without tracheoesophageal fistula (TEF), duodenal and proximal small bowel atresias, congenital diaphragmatic hernia (CDH), and gastroschisis/omphalocele all predispose to the development of GERD. The consequences of GERD in children can lead to the same complications seen in adults (erosive esophagitis, stricture, and Barrett esophagitis) but also include pulmonary effects (reactive airway disease and pneumonia), potential malnutrition secondary to the inability to maintain adequate caloric intake, and apneic episodes leading to ALTE spells.

Barriers Against GERD

The most important factor for preventing reflux of gastric contents into the esophagus is the LES. Embryologically, the LES arises from the inner circular muscle layer of the esophagus, which is asymmetrically thickened in the distal esophagus. This thickened muscle layer creates a high pressure zone that can be measured manometrically. In addition, this muscular thickening extends onto the stomach, more prominently on the greater than lesser curvature. The phrenoesophageal membrane, arising from the septum transversum of the diaphragm and the collar of Helvetius, holds the LES in position. The result is an LES that lies partially in the chest and partially in the abdomen. This positioning is important for the normal barrier function against GER. Esophageal manometry can identify this transition (which is known as the respiratory inversion point) from the thoracic to the abdominal esophagus.

The LES is an imperfect valve that creates a pressure gradient in the distal esophagus. The ability to prevent GER is directly proportional to the LES pressure and its length, provided that LES relaxation is normal. In an adult study, LES pressures >30 mmHg prevented GER, as documented by 24-hour pH study, whereas pressures between 0 and 5 mmHg correlated with abnormal pH studies in more than 80% of patients. Also, GER is statistically significantly more likely to develop in adults if the LES pressure falls below 6 mmHg at the respiratory inversion point or if the overall LES length is ≤2 cm. As noted previously, the LES is relatively fixed across the esophageal hiatus by its surrounding attachments. Malposition of the LES, which can occur with a hiatal hernia or abnormal development, results in loss of the protective function of the LES, resulting in GER. Finally, LES relaxation occurs with esophageal peristalsis initiated by the swallowing mechanism. This relaxation is normal and must occur. When children with symptoms of GER were studied with pH and manometry simultaneously, reflux episodes rarely correlated with decreased LES pressures. Rather, the majority of reflux episodes occurred during transient LES relaxations, and no reflux episodes were identified during LES relaxation after swallowing with normal peristaltic movement.

In summary, although the barrier function of the LES is imperfect, it can be highly effective. Short LES length, abnormal smooth muscle function, increased frequency of transient LES relaxations, and LES location within the chest can contribute individually (or in combination) to LES failure and GERD.

Another barrier to the development of symptomatic GERD is the intra-abdominal length of the esophagus. Although no absolute effective intra-abdominal esophageal length has been identified that prevents GER, correlation between several lengths and GER have been identified. In one report, an intra-abdominal length of 3–4.5 cm in adults with normal abdominal pressure provided LES competency 100% of the time. A length of 3 cm was sufficient in preventing reflux in 64% of individuals, whereas a length of <1 cm of intra-abdominal esophagus resulted in reflux in 81% of patients. It has been believed that failure to mobilize adequate esophageal length for intra-abdominal positioning during antireflux operations can lead to less than successful results or recurrent GER in adults. However, we now know these data are not applicable in infants and children, and that complete mobilization of the esophagus, in the absence of a hiatal hernia, is detrimental in infants and children through the results of two multicenter, prospective, randomized trials.

A third barrier to reflux is the angle of His, which is the angle at which the esophagus enters the stomach. The usual orientation is that of an acute angle, which creates a flap valve at the gastroesophageal junction. Although the actual functional component of the angle of His is not well known, it has been shown to provide resistance to GER. Experimentally, when this angle is more obtuse, GER is more prone to develop. Conversely, accentuation of the angle inhibits GER.

The ability of the angle of His to prevent GER may be diminished as a result of abnormal development or may be iatrogenic, as occurs after gastrostomy placement. When a normal angle of His is present, there is a convoluted fold of mucosa present at the gastroesophageal junction. This mucosa creates a rosette-like configuration that collapses on itself with increases in intragastric pressure or negative pressure in the thoracic esophagus, thus acting as an additional weak antireflux valve.

Patients with increased abdominal pressure as a result of neurologically related retching, physiologic effects (obesity, ascites, peritoneal dialysis), or anatomic abnormalities (gastroschisis, omphalocele, CDH) are at increased risk for developing GERD owing to the effects of chronic pressure from the abdomen into the thorax. Finally, certain congenital defects such as congenital short esophagus, congenital hiatal hernia, and EA/TEF predispose to GERD. In patients with EA/TEF, the esophagus has abnormal peristalsis and the LES is incompetent. It has been reported that up to 30% of these patients will require antireflux surgery after repair of their EA/TEF. Regarding CDH, anatomic abnormalities of the esophageal hiatus and the esophagus predispose to GERD, with 15–20% of surviving patients undergoing an antireflux operation for GERD.

Once the barrier to GER has been overcome (or failed), mechanisms for esophageal clearance become important in preventing damage associated with exposure of the esophageal mucosa to the gastric refluxate. The primary mechanism for esophageal clearance remains esophageal motility. However, gravity and saliva contribute to the ability of the esophagus to clear the refluxate. There are three types of esophageal contractions: primary, secondary, and tertiary. Primary contraction waves are initiated with swallowing and are responsible for the clearance of refluxed contents in 80–90% of reflux episodes. Secondary waves occur when material is refluxed into the esophagus and clearance is required, especially when the reflux occurs during sleep. Tertiary waves have nothing to do with esophageal clearance and are sporadic, nonpropagating contractions. When impaired esophageal motility is present as a result of abnormal smooth muscle function, impaired vagal stimulation, or obstruction, refluxed gastric contents are not moved caudad into the stomach in a timely manner. This prolonged exposure can lead to esophageal mucosal injury and can potentiate the motility disturbance due to vagal and/or smooth muscle inflammation or injury. Saliva neutralizes refluxed material, and patients with GERD have been found to have decreased salivary function. It has also been shown that positional effects of GERD treatment may be related to gravity assisting in the clearance of esophageal refluxate.

The final element for prevention of esophageal injury related to GERD is the ability to limit injury once refluxed contents have reached the esophagus. In addition to functioning as a neutralizing agent, saliva also aids in lubricating the esophageal contents, thus making it easier to clear any retained refluxate. Acid exposure has traditionally been postulated to cause the most significant injury, but more recent data have also implicated alkaline bile reflux. Some pediatric patients with documented GERD have been shown to have increased acid secretion. To this end, the role of PPIs in controlling GERD in this population is very important because they have the dual effect of increasing the gastric pH while simultaneously decreasing the acid volume. However, it is now recognized that many children with GERD have normal pH probe studies and acid reflux with esophageal injury is not as important an issue for this subset of patients. Other substances that increase esophageal mucosal injury include bile salts, pepsin, and trypsin. When combined with acid, bile salts are injurious to the esophageal mucosa by increasing the permeability of the esophageal mucosa to existing acid, thus further potentiating injury. Pepsin and trypsin are both proteolytic enzymes that can injure the esophageal mucosa. Both of these enzymes are more toxic at lower pH levels and, hence, are more injurious in the presence of acid reflux.

Clinical Manifestations

The presentation of GERD in infants and children is variable and depends on the patient’s age and overall medical condition. The surgeon must consider both this variability and the patient characteristics when evaluating a child with symptoms of possible GERD. Although the symptoms of GERD are variable for each patient, the actual frequency of symptoms seen in infants who have required surgical intervention for GERD has been reported ( Table 28.2 ).

When considering the symptoms associated with GERD, persistent regurgitation is the most common complaint reported by parents of children with GERD. However, in infants, vomiting is often physiologic and can be “normal.” This type of vomiting is termed chalasia of infancy and is seen early in life, usually during burping, after feeding, or when placed in the recumbent position. Chalasia does not interfere with normal growth or development, and rarely leads to other complications. It is a self-limited process, with most infants transitioning to being asymptomatic by 2 years of age or near the time of initiating solid foods. No treatment is necessary in patients who have chalasia, and no diagnostic evaluation should be pursued. However, when persistent regurgitation is the result of GER, it can lead to complications, including significant malnutrition and growth failure due to insufficient caloric intake.

In infants, another presenting symptom is irritability due to pain. Painful esophagitis can be the result of the reflux. Discomfort leads to crying despite consoling measures. Occasionally, small volumes of feeds briefly assist in alleviating pain. However, this is generally not a lasting effect. In contrast to infants, children with GERD more often present with complaints of pain. As with adults, the pain is retrosternal in nature and often described as heartburn. Long-standing GERD with esophagitis can lead to chronic inflammation or even ulcer formation with eventual scarring and stricture. Dysphagia develops as a result of a narrowed esophageal lumen, as well as possible esophageal dysmotility secondary to long-standing mucosal inflammation. Obstructive symptoms and pain are the two most common associated complaints when an esophageal stricture is present.

Barrett esophagitis is a premalignant condition that is associated with prolonged GERD. It occurs when metaplasia develops in the esophageal squamous epithelium that is replaced with columnar epithelium. In adults, it is thought to be the result of chronic esophageal injury. Whether it develops from gastric acid injury or exposure to alkaline reflux is currently a controversial topic. Although uncommon in infants and children, when it does develop, serious complications often result. In addition to the increased risk for adenocarcinoma, approximately 50% of these patients will develop stricture and many patients will develop ulcers. Aggressive GERD management, along with vigilant long-term surveillance via yearly esophagogastroscopy, should be pursued to minimize these often difficult and possibly fatal complications.

Respiratory symptoms are commonly seen in infants and children. Delineating the role of GER as an etiologic agent for ongoing respiratory complaints can be difficult because of the similarity of the symptoms that are seen with other pulmonary diseases and the fact that primary aspiration from oropharyngeal dysmotility, rather than GER, may be the inciting factor. Chronic cough, wheezing, choking, apnea, or near sudden infant death syndrome (SIDS) can all be symptoms attributable to GER. Recurrent bronchitis or pneumonia can occur from aspiration of the refluxate. Esophageal stimulation via acidification of the esophageal mucosa causes vagally mediated laryngospasm and bronchospasm, which clinically presents as apnea or choking, or mistakenly as asthma. Esophageal inflammation, as seen with esophagitis, likely enhances this mechanism. The effects of GER on premature infants with respiratory problems have been studied. Most of these infants were intubated for varying periods owing to respiratory distress syndrome or bronchopulmonary dysplasia. In the former group, GERD was responsible for deteriorating pulmonary status requiring intubation. In the latter, deterioration of pulmonary status plus failure to thrive and anorexia led to the diagnosis of GERD. All improved with correction of the GERD.

Although uncommon, hemorrhage can be a presenting symptom of GERD. Esophagitis, gastritis, and ulcer formation can lead to hematochezia or melena in a small percentage of infants or children.

Medical Management of GER

Several recent articles have discussed management of GER in infants and children. These articles describe nonpharmacologic therapies for GER, which include parental reassurance, dietary modification, and positional adaptation. Reassurance, by showing compassion for the presumed impaired QOL for their infant, is important. Dietary modifications have been suggested to reduce regurgitation to a greater extent and faster than natural evolution. Thickening the formula to help reduce regurgitation has been approved as a management strategy by both the European and North American Societies for Pediatric Gastroenterology. Positional adaptation includes the prone position, the immediate right side position with later left side after feeding, and supine 40° anti-Trendelenburg (supine with head in the air). However, the prone position is no longer recommended owing to the increased risk of sudden infant death.