Gastroesophageal reflux (GER) is defined as passage of gastric contents into the esophagus. GER is a normal physiologic process that occurs throughout the day in healthy infants, children, and adults. Gastroesophageal reflux disease (GERD) occurs when gastric contents reflux into the esophagus or oropharynx and produce symptoms. Regurgitation is defined as passage of refluxed gastric contents into the oral pharynx. Vomiting is defined as expulsion of the refluxed gastric contents from the mouth. During infancy, GER is common and most often manifests as vomiting. Vomiting resolves spontaneously in nearly all healthy infants within the first 18 months of life.
The lower esophageal sphincter (LES) constitutes the major barrier to GER. The LES is a specialized region of smooth muscle that is tonically contracted. In the healthy adult, this region is about 3 cm in length and located at the level of the diaphragm. In the neonate, the sphincter length is about 1.5 cm and it is located about 2 cm above the level of the diaphragm. In the older child and adult, the crus of the diaphragm (skeletal muscle) contracts during inspiration and increases the high-pressure barrier in the region of the LES. Other anatomic components of the antireflux barrier include the phrenoesophageal ligament, which anchors the distal esophagus to the crural diaphragm , and the angle of His . References 1. Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med 1997;336:924-32. 2. Bardaji C, Boix-Ochoa J. Contribution of the His angle to the gastroesophageal antireflux mechanism: an experimental study in dogs. Pediatr Surg Int 1986;1:172-6. ALSO: Esophageal clearance, AND
The most frequent mechanism underlying GER in children of any age is a transient relaxation of the lower esophageal sphincter . A transient LES relaxation is an abrupt decrease in LES pressure to the level of intragastric pressure that is unrelated to swallowing . It is accompanied by inhibition of the esophageal body and crural diaphragm, and it is of relatively longer duration than relaxations triggered by a swallow . The tracings in this slide show a normal swallow-induced LES relaxation (left) and transient LES relaxation (at the bar line) followed by a clearance swallow. About 5 seconds before the onset of acid reflux (see pH tracing at top), the LES relaxes completely (LES tracing) in the absence of swallowing (pharyngeal tracing). This relaxation is much longer than a normal swallow-induced relaxation (depicted at left). With esophageal acidification, esophageal-body pressure rises, indicating flow into the esophagus. Tracings reprinted with permission from Kawahara et al, 1997 . References 1. Kawahara H, Dent J, Davidson G. Mechanisms responsible for gastroesophageal reflux in children. Gastroenterology 1997;113:399-408. 2. Mittal RK, Holloway RH, Penagini R, Blackshaw LA, Dent J. Transient lower esophageal sphincter relaxation. Gastroenterology 1995;109:601-10.
A number of factors contribute to the frequency of regurgitation in infants. A shorter esophagus, the small capacity of the esophagus, and recumbent posture (lack of gravity) make it more likely that refluxed material in the infant will fill the esophagus and pass into the pharynx. The infant is thus more likely to regurgitate than the adult when gastric contents empty into the esophagus. The esophagus is approximately 11 cm at birth, with a diameter of 5 mm. By adulthood, the esophagus is 24-30 cm long, with lateral and anteroposterior diameters of 30 and 19 mm, respectively . Reference 1. Weaver TL. Anatomy and embryology. In: Walker WA, Durie PR, Hamilton JR, et al, eds. Pediatric Gastrointestinal Disease , 1st ed. Philadelphia: BC Decker; 1991:195-216.
In healthy individuals, a series of barriers and protective responses prevent refluxed gastric contents from entering the airway. These protective mechanisms include the upper esophageal sphincter (UES), esophageal-glottal closure reflex, apnea and pharyngeal clearance, and cough and airway clearance of aspirated materials . Distention of the upper esophagus can lead to different actions. When the refluxate is of small volume, the UES contracts. When there is large-volume refluxate, esophageal distention leads to vagal reflexes that cause vocal cord closure, central apnea, and UES relaxation. The UES opens, followed by entry of gastric contents into the pharynx, followed by a swallow to clear the pharynx. Respiration subsequently resumes. If any of this complex sequence occurs out of order, there is a high risk of aspiration. If refluxate enters the larynx, a cough expels the material from the airway and bronchoconstriction prevents aspirated material from reaching the alveolar spaces. Reference 1. Lang IM, Medda BK, Shaker R. Mechanisms of reflexes induced by esophageal distension. Am J Physiol 2001;281:G1246-63.
GERD is a multifactorial disorder. The most frequent mechanism underlying GER is a transient LES relaxation . Other potential factors contributing to GER including an increase in intra-abdominal pressure, such as caused by straining; reduced esophageal capacitance; and decreased gastric compliance. It is controversial whether a delay in gastric emptying contributes to GERD [2, 3]. A number of mechanisms can contribute to esophageal complications of GER, including impaired esophageal clearance, the noxious composition of refluxate, and defective esophageal tissue resistance. The squamous epithelium of the esophagus has intrinsic defense mechanisms that protect against injury by luminal acid . However, in adults with non-erosive reflux disease, a widening of the gap junctions between adjacent squamous epithelial cells was described on electronic microscopy of distal esophageal mucosa . These changes are likely due to gastric acid and pepsin and not a primary abnormality . Mechanisms of airway complications of GER include vagal reflexes and impairment of airway protection. References 1. Kawahara H, Dent J, Davidson G. Mechanisms responsible for gastroesophageal reflux in children. Gastroenterology 1997;113:399-408. 2. Omari T, Barnett C, Benninga M, Lontis R, Goodchild L, Haslam R, Dent J, Davidson G. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut 2002 (in press). 3. Ewer AK, Durbin GM, Morgan ME, Booth IW. Gastric emptying in preterm infants. Arch Dis Child Fetal Neonatal Ed 1994;71:F24-7 4. Orlando RC. Mechanisms of reflux-induced epithelial injuries in the esophagus. Am J Med 2000;108(suppl 4a): 104-8S. 5. Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology 1996;111:1200-5. 6. Dent J. Gastro-oesophageal reflux disease. Digestion 1998;59:433-45.
Esophageal pH monitoring measures the frequency and duration of acid reflux episodes and is used widely as an index of esophageal acid exposure. It is useful for establishing the presence of abnormal acid reflux, for determining whether there is a temporal association between acid reflux and frequently occurring symptoms, and for assessing the adequacy of dosage of histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) in unresponsive patients. It may be used to determine if a patient is at increased risk for airway complications of GER. This test cannot detect non-acidic reflux episodes, such as occur postprandially in infants, or GER complications such as an apparently life-threatening event (ALTE) or aspiration pneumonia when they are associated with brief reflux episodes that are within the range of “normal” GER. Esophageal pH monitoring is useful for detecting apnea only if performed simultaneously with measurement of respiration and chest wall movement.
Esophagogastroduodenoscopy (EGD) enables visualization and biopsy of the esophageal epithelium. EGD and biopsy can determine the presence and severity of esophagitis, stricture, and Barrett’s esophagus, as well as exclude other disorders, such as eosinophilic or infectious esophagitis. Limitations include the need for sedation or anesthesia. Grading systems for the severity of erosive esophagitis, such as the Los Angeles classification , have not yet been validated in pediatric patients. There is a poor correlation between endoscopic appearance and histopathology. Therefore, esophageal biopsy is recommended when diagnostic endoscopy is performed. In general, EGD is not useful for extraesophageal manifestations of GERD. Hetzel-Dent grade 4 erosive esophagitis; endoscopic view courtesy of Benjamin D. Gold, MD. Reference 1. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45:172-80.
Several mechanisms have been postulated to explain respiratory complications in GER patients. According to one theory, respiratory symptoms due to GER are attributed to aspiration or microaspiration of gastric contents during a reflux episode (see diagram at left). Another proposed mechanism for GER-induced respiratory symptoms is a reflex arc, by which GER causes esophageal irritation and the irritation (stimulation of esophageal afferent receptors by acid) leads to laryngospasm or bronchospasm (triggered by airway efferents) via vagal pathways (see diagram at right). In two studies, increased vagal activity was demonstrated in a majority of asthmatic patients with GER [1, 2]. References 1. Schan CA, Harding SM, Haile JM, et al. Gastroesophageal reflux-induced bronchoconstriction: an intraesophageal acid infusion study using state of the art technology. Chest 1994;106:731-7. 2. Lodi U, Harding SM, Coghlan C, et al. Autonomic regulation in asthmatics with gastroesophageal reflux. Chest 1997;111:65-70.
The objectives of antireflux surgery are to restore the intra-abdominal portion of the esophagus, approximate diaphragmatic crurae, and reduce hiatal hernia when present. Fundoplication, which is the wrapping of the fundus around the LES, is commonly performed by the Nissen method (a 360 wrap). The results of pediatric series of laparoscopic fundoplication suggest that outcome and complication rates are similar to those with the open procedure, but the hospital stay is shortened . Reference 1. Rothenberg SS. Experience with 220 consecutive laparoscopic Nissen fundoplications in infants and children. J Pediatr Surg 1998;33:274-8.
Gastroesophageal Reflux in Infants and Children
Swallowing reflex begins at 16 weeks gestation
Can suckle by 2 nd to 3 rd trimester
34 weeks, infant can suckle and feed normally
Pharyngeal phase earlier developed
Oral preparatory phase maldeveloped in premature infants
Definitions GER Involuntary passage of gastric contents into esophagus GERD Symptoms or complications that may occur when gastric contents reflux into esophagus or oropharynx Regurgitation Passage of refluxed gastric contents into oral pharynx Vomiting Expulsion of refluxed gastric contents from mouth
Airway Protective Mechanisms Vagal reflexes Vocal cords close Central apnea occurs UES relaxes 0.15 s Refluxate enters pharynx 0.3 s Swallowing clears pharynx 0.6 s Small volume 1.0 s Respiration resumes Large volume ESOPHAGEAL DISTENTION UES contracts
Principles of Antireflux Surgery Restore intra- abdominal segment of esophagus Approximate diaphagmatic crurae Reduce hiatal hernia when present Wrap fundus around LES to reinforce antireflux barrier