GERD

Gastroesophageal reflux (GER) is a physiologic phenomenon that occurs at all ages but more frequently in infants. When this retrograde movement of gastric contents into the esophagus causes troublesome symptoms or complications it is referred to as GERD. The refluxed material may be air (belch), liquid, solid, or mixed; and, depending on the pH, may be acid (pH ≤4) or nonacid. The relative proportion of acid and nonacid reflux episodes was not known until the advent of the combined pH-impedance technology. This was mainly because the conventional pH probe study only measured episodes that were acid. We now know that nonacid reflux episodes are at least as frequent as acid episodes and are capable of producing symptoms as well.

The lower esophageal sphincter (LES) is the most important physiologic antireflux barrier. The LES is a high-pressure zone maintained by two muscular systems that help keep gastric contents from refluxing into the esophagus. The first is the circular (smooth) muscle layer of the lower end of the esophagus primarily innervated by the intrinsic enteric nervous system. The second is the sling (skeletal) muscle of the diaphragmatic crura that envelops this area and is supplied by the phrenic nerve as well as inhibitory (nitrenergic) motor fibers from the myenteric neurons. The LES is normally situated in the abdominal cavity below the diaphragm and the relative higher pressure in the intra-abdominal cavity over the intrathoracic pressure adds to the sphincter mechanism of the LES. Displacement of the LES into the thoracic cavity in a patient with hiatal hernia therefore disrupts proper functioning of the LES and predisposes to GERD.

Once the refluxed material enters the esophagus, the bolus causes distension of the wall and stimulates the receptors which induce a neurally mediated peristaltic contraction that moves the refluxate back into the stomach. This secondary peristalsis is often supplemented by a swallow-induced primary peristaltic wave that helps clear the esophagus. These clearance or “stripping” waves are an important mechanism for preventing damage to the esophageal mucosa from prolonged contact with the refluxed material. Another physiologic barrier to reflux-induced esophageal damage is reflex swallowing of alkaline saliva in response to a GER episode that helps neutralize acid content of the refluxate. GER-induced swallowing as well as clearance peristaltic waves are inhibited during sleep such that increased nocturnal reflux episodes tend to be more harmful to the mucosal lining.

The physiologic basis for most GER events is a phenomenon referred to as transient lower esophageal sphincter relaxation (TLESR). This brief relaxation of the LES can be triggered by distension of the gastric fundus and is mediated through the vagus nerve. TLESR can result in reflux of air (belch), liquid, solid, or mixed gastric contents into the esophagus. In infants, reflux episodes occur more often and are likely due to frequent feeds that distend the fundus causing more TLESR events. Anatomy of the stomach and gastroesophageal junction and the more frequent recumbent posture also predispose infants to more reflux episodes. When the refluxed material enters the short esophagus of an infant, it usually travels the entire length up to the pharynx and presents as regurgitation or vomiting. Full-column reflux episodes, and GER episodes in general, decrease as the child grows owing to esophageal lengthening and transition of the anatomy of the stomach and gastroesophageal junction to a more adult-like configuration.

The classic symptoms of GERD include heartburn, regurgitation, and retrosternal pain. Extraesophageal symptoms attributed to GERD include cough, hoarseness, back arching, asthma, sinusitis otitis media, apnea, bradycardia, apparent life-threatening events, and dental erosions. Symptoms of GERD, however, vary by age and the description of intensity, localization, and severity may be unreliable until the age of at least 8 years, and sometimes even later, especially in children with NDD. Distinguishing physiologic reflux from GERD when symptoms become “troublesome” remains challenging in younger children and those with NDD as they may not present with the typical symptoms of GERD nor manifest any objective evidence of its complication. As an example, excessive crying in infants and toddlers may be misdiagnosed as GERD and treated with acid suppression agents without resolution of the troublesome symptom. The alarm symptoms that are indicative of a complication of GERD include weight loss or poor weight gain, dysphagia, bleeding, anemia, choking, and feeding difficulties. Children presenting with these symptoms warrant further evaluation. Risk factors for severe GERD include history of central nervous system (CNS) impairment, esophageal atresia or tracheoesophageal fistula repair, chronic lung diseases, and diaphragmatic or hiatal hernia.

Dysphagia may be the sole presenting symptom of reflux esophagitis in children even in the absence of a typical history suggestive of GER. Dysphagia has been reported in more than 30% of adults with GERD. The swallowing difficulty in these adult patients with reflux esophagitis was felt not to be due to abnormal motility of the striated muscle of the proximal esophagus but more likely from inflammation of the distal esophagus. Distal esophageal mucosal injury occurs in GERD because acid clearance is slower in this region, placing it at an increased risk of developing esophagitis.

Even though the typical symptoms are present in 82%–97% of subjects with endoscopically proven esophagitis, their positive and negative predictive values are low and therefore are not recommended for screening purposes. Symptom scores in adults with GERD correlated with the number of reflux episodes but not with the total acid exposure time. Studies in adult patients with GERD have reported that LES pressure and esophageal acid exposure time are poor predictors for disease severity, but hiatal hernia was shown to exert a much stronger influence on the severity of erosive reflux disease.

It is well documented that GER decreases threshold for perception of visceral pain in the esophagus. Somatic pain hypersensitivity after tissue injury has two important properties, first it manifests as allodynia or hyperalgesia, and second it is diffuse, present not only at the site of injury but also surrounding healthy tissue. For example it has been shown that acid infusion to the lower esophagus induces a decrease in pain threshold in the lower and upper esophagus as well as in the anterior chest wall due to a change in sensory processing within the CNS. Healthy individuals can develop persistent visceral (esophageal) hypersensitivity as a result of peripheral and central sensitization after acid or alkaline injury to the esophagus, such that physiologic GER (acid or nonacid), or even eating or drinking can be sufficient to induce pain referred to the chest.

Infants with crying and feeding disorders are perceived as more vulnerable by their parents and depending upon parental perceptions, experience, coping skills, and psychosocial conditions, are often brought to medical attention. A study of infants seen in clinic for a complaint of crying and fussiness reported that they had more feeding difficulties, were less responsive to treatment, and had more maternal stress. Up to 70% of infants have physiologic regurgitation (spit-ups) that resolves without intervention in 95% of them by 12-months-of-age. When given a history of “vomiting” it is important to differentiate between regurgitation and vomiting because the latter is more likely to be pathologic and may need to be evaluated more urgently. Unlike vomiting, regurgitation has no CNS emetic reflex, retrograde intestinal contractions, nausea, or retching. In infants, however, because of a short esophagus, most reflux episodes tend to project as “vomiting” and are commonly reported as such by parents. A history of regurgitation was found to be neither necessary nor sufficient for a diagnosis of GERD owing to its lack of sensitivity and specificity.

When compared with older children, those less than 5-years-old with GERD tend to present more often with food refusal, regurgitation, vomiting, and abdominal pain. Young children with a history of vomiting after feeding (GERD or other reasons) may have difficulty in accepting feeds, despite having no alteration of oral and pharyngeal phases of swallowing. The proposed hypothesis to explain this is that initial acid exposure of the mucosal chemoreceptors and nerve endings in the esophagus triggers afferent signals to the spinal nerves that are transmitted to the brain which perceives the sensation as pain or discomfort. The neurochemical alterations induced in this pathway by repeated reflux episodes appear to persist even after the initial noxious stimulus (vomiting, GERD) resolves and leaves the child with a hypersensitivity to any bolus movement along the esophagus, including swallowing food. Peripheral and central sensitization are believed to be important mechanisms for this ongoing heightened perception of esophageal sensation (visceral hypersensitivity) resulting in food refusal.

Older children are able to give an appropriate history of heartburn and regurgitation thereby making the diagnosis of GERD easier. A community pediatric practice survey showed that 5.2% of children aged 10 to 17 were able to report a burning or painful feeling in the middle of the chest, 8.2% reported regurgitation, 5% reported epigastric pain, and 3.6% actually reported odynophagia. In adolescents, the underlying pathophysiology and symptom presentation of GERD are similar to adults. The predominant symptoms of GERD in children ages 6 to 17 years was reported to be regurgitation or vomiting, cough and epigastric pain, or heartburn. In another study, 18% of children with GERD reportedly presented with retrosternal pain. For unclear reasons, nonerosive reflux disease is more common in symptomatic children with GERD, but erosive esophagitis is reported in more than one-third of pediatric-age patients with underlying GERD-promoting disorders. These risk factors that predispose to severe reflux disease include CNS impairment, esophageal atresia, chronic lung disease, hiatal hernia, and congenital diaphragmatic hernia. Helicobacter pylori was previously thought to be protective of GERD by causing atrophic gastritis and a decrease in gastric acid secretion, but recent evidence shows a high prevalence of esophagitis in pediatric patients with H pylori infection.

Evaluation

An upper GI contrast study is indicated if there is a history of vomiting, dysphagia, or odynophagia. It should not be done to diagnose GERD but to rule out conditions that may mimic GERD such as structural disorders of the upper GI tract.

In younger children and those with neurodevelopmental disabilities presenting with food refusal, a thorough evaluation of the oral, pharyngeal, and esophageal phases of swallowing and a videofluoroscopic study of swallowing (VFSS) should be performed by a speech pathologist. If there is suspicion or evidence of aspiration, a bronchoscopy with bronchoalveolar lavage should be considered and could be combined with an esophagogastroduodenoscopy (EGD).

Multichannel intraluminal impedance (MII) combined with a pH sensor can detect esophageal bolus flow, determine its direction, quantify the number of reflux episodes and characterize them as acid (pH <4) and nonacid (weakly acidic and weakly alkaline). It can also establish proximal extent of the reflux, and provide information on bolus and acid clearance. A pH-MII identifies more reflux events than conventional pH probe study and improves clinical correlation with symptoms. This is important in children who cannot reliably convey the classic GER symptoms or those who have extraesophageal symptoms attributed to GERD.

In our institution, the authors retrospectively reviewed combined pH-MII studies from 186 infants. In 20 studies, a total of 60 episodes of perceived pain-related symptoms (back arching, crying, restlessness, head side-to-side, thrashing, pain, screaming, and fussiness) were reported by the caregiver but only 38% were associated with GER episodes, all of which were nonacid. Therefore, contrary to popular belief, GER does not appear to play a major role in infants perceived to have pain-related symptoms. In addition to being helpful in associating GER with perceived pain episodes and atypical (extraesophageal) symptoms, pH-MII is also indicated in children that report classic symptoms of GER that are refractory to acid suppression with proton pump inhibitors (PPI). In this situation the study can be done while on acid suppression therapy to evaluate the relationship between persistent symptoms and GER. An adult study showed that persistent symptoms on PPI therapy are either associated with nonacid reflux or are not associated with reflux at all. Our infant study was similar in that we also found that nonacid reflux events are as likely as acid reflux events to be associated with a symptom.

The role of EGD is to rule out other causes of esophagitis and heartburn ( Box 1 ). It has been reported that no correlation exists between symptoms and endoscopic esophageal findings. A recent study reported that children referred to a cardiology clinic for chest pain had positive endoscopic findings if there was epigastric tenderness on physical examination. Erosive esophagitis ( Fig. 1 ) has been noted to be more common in males and increases with age. A hiatal hernia ( Fig. 2 ) is the only endoscopic observation that predicted the presence of erosive esophagitis, consistent with studies in adults. Although GER symptom frequency and intensity correlate with severity of mucosal injury, neither will predict the severity in the individual patient. However, when pain is epigastric or mesogastric in location, acid-peptic disorders are high on the differential.

Box 1

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  Weakly acid reflux

  
  
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  Weakly alkaline reflux

  
  
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  Gas

  
  
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  Duodeno-gastroesophageal reflux

  
  
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  Eosinophilic esophagitis

  
  
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  Pill esophagitis

  
  
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  Infection

  
  
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  Crohn disease

  
  
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  Functional heart burn or dyspepsia

Causes of heartburn

Distal esophageal peptic erosions in a child with NDD.

Hiatal hernia in a child with GERD symptoms.