Although the basic function of the esophagus is to simply propagate a bolus of food from the oropharynx to the stomach, the execution of this function remains complex. Ultimately, the swallow mechanism is a dynamic process between the muscles of the esophagus and its neural innervation, and involves the interplay between the upper esophageal sphincters (UESs) and lower esophageal sphincters (LESs).

The esophagus is a hollow tube, usually between 17 and 30 cm but averaging 23 cm.¹ At the proximal end is the UES, which is approximately 1 cm in length. The UES is composed of striated cervical esophageal muscle, the cricopharyngeus, and the inferior pharyngeal constrictor muscles. The superior and inferior hyoid muscles and superior pharyngeal muscles also help facilitate UES opening. Innervation of the UES arises from branches of the vagus nerve stemming from the nucleus ambiguus. Tonic closure of the UES functions to prevent insufflation of air during inspiration and esophagopharyngeal reflux. Intermittent relaxation of the UES allows bolus transit and venting (belching).

The esophageal body is composed of two different types of myocytes. Although somewhat variable, in general, the proximal third of the esophagus is striated muscle and the distal two-thirds composed of smooth muscle. The transition is not abrupt, and thus there is a short segment in which the muscles fibers are mixed. The arrangement is such that there is an outer longitudinal muscle layer and an inner circular muscle layer. This arrangement facilitates peristalsis, which will be discussed below.

Between the longitudinal and circular muscle layers lies the myenteric or Auerbach’s plexus. This network of neurons contains ganglia arising from the vagus nerve, although the concentration of ganglia affecting the smooth muscle portion is higher than the striated muscle portion. Ganglia innervating striated muscle stem from the nucleus ambiguus while ganglia innervating smooth muscle stem from the dorsal motor nucleus of the vagus. The neurotransmitter acetylcholine plays a role in activation of both striated and smooth muscles in the esophagus. Acetylcholine released by nerve endings activates the esophageal striated muscle. Postganglionic neurons in the distal esophagus activate smooth muscle cells by releasing acetylcholine. Inhibitory innervation of esophageal smooth muscle, which induces relaxation, is achieved by the release of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) from postganglionic nerve endings. The myenteric plexus is interconnected with Meissner’s plexus, which is located in the submucosa and is responsible for innervation of the circular muscle layer and muscularis mucosa.

Sensory information is relayed in a dual manner via both vagal and spinal nerves. Esophageal sensation is extremely complex and beyond the scope of this chapter. In short, sensory information in the esophagus is relayed from either muscular afferent receptors or mucosal afferent receptors. In general, muscular afferent fibers respond to intraluminal distention. The pressure threshold leading to sensory nerve firing, and the rate of spontaneous firing, differs among vagal and spinal afferent neurons. In contrast, mucosal afferent fibers do not respond to distention but rather touch and chemical irritation by acid, bile, and other agents.²

The LES is a 2- to 4-cm high-pressure zone that provides a barrier between the distal tubular esophagus and stomach, composed of intrinsic circular muscles of the esophagus and extrinsic muscles from the crural diaphragm. Motor innervation again stems from the vagus nerve with preganglionic nerves releasing acetylcholine. The LES contracts in response to postganglionic excitatory neurons releasing acetylcholine. The LES relaxes with postganglionic inhibitory neurons releasing NO or VIP. The LES is tonically contracted and relaxes via reflex mechanisms in response to a swallow. The LES also relaxes in response to vomiting, belching, rumination, and transient LES relaxations (TLESRs). TLESRs are seen in normal patients and are increased in patients with gastroesophageal reflux disease (GERD). TLESRs also increase in response to gastric distention via reflex pathways.

Bolus transport occurs with peristalsis of the esophagus. Voluntary oropharyngeal deglutition triggers UES relaxation. Once the bolus enters the esophagus, the UES closes and the esophageal phase of swallowing takes over. The swallow event triggers primary peristalsis, or sequential esophageal muscle contractions, which occlude the esophageal lumen. Primary peristalsis propels the bolus forward down the esophagus, and a pressure of at least 20 mm Hg is needed to propel the bolus forward. Contraction of the longitudinal muscles also occurs, shortening the esophagus by approximately 2 cm. The peristaltic wave has a velocity of 3 cm/s in the upper esophagus, 5 cm/s in midesophagus, and 2.5 cm/s in the lower esophagus. With multiple rapid swallows, peristalsis remains inhibited until the last swallow. The control of primary peristalsis is centrally mediated.

Secondary peristalsis is triggered with luminal distention for the purpose of clearing residual bolus material due to ineffective primary peristalsis or reflux events. Pharyngeal contraction and UES relaxation are not seen in secondary peristalsis. The control of secondary peristalsis is intrinsic to the esophagus and is not centrally mediated. Local afferent sensory neurons respond to luminal distention and trigger contractions above the area of distention and relaxation below, moving the bolus forward.³

Barium Studies of the Esophagus

A barium esophagogram, also called a barium swallow, is a radiology test with the ability to help diagnose structural lesions of the esophagus as well as to assess function. In a double-contrast esophagogram, the patient ingests an effervescent agent to distend the esophagus. Next, high-density barium is swallowed in the upright position to obtain full views of the esophagus. Structural lesions may be seen including strictures, diverticula, webs, masses, and even esophagitis. Fluoroscopic views of the patient swallowing barium boluses while prone are used to evaluate esophageal motility.⁴

Certain features identified on barium esophagogram are indicative of primary esophageal motility disorders. The classic esophagogram in achalasia shows a dilated esophagus with a “bird’s beak” narrowing of the distal esophagus. In advanced cases, the esophagus may appear massively dilated or tortuous, hence called sigmoid esophagus.⁵ With this classic barium study appearance and an EGD to rule out pseudoachalasia, some argue manometry studies are not needed to diagnose achalasia⁴; however, this remains controversial. A barium esophagogram performed in patients with diffuse esophageal spasm (DES) will show a classic “corkscrew” esophagus. DES manifests as repetitive nonperistaltic contractions that may obliterate the lumen. However, this classic finding is seen in less than <15 percent of patients with DES.⁴

The addition of a dynamic recording using video, called a “video fluoroscopic swallow study” or “cine-esophagogram,” evaluates the pharyngeal phase of the swallow. Therefore, patients with symptoms of oropharyngeal dysphagia should have a cine-esophagogram instead of just a barium swallow.

Esophageal Scintigraphy

Another noninvasive image-based modality used to evaluate esophageal function is esophageal scintigraphy. This nuclear medicine study uses a radiolabeled meal to evaluate esophageal transit and clearance. The study uses a gamma camera, also called a scintillation camera, to image ingested radioisotopes. Although a variety of protocols are available, the basic premise of the study includes ingestion of a technetium-99m–labeled substance, like water, cornflakes, or applesauce, by the patient. Events are recorded at short intervals to assess bolus transport from the oropharynx to stomach. The test can be performed upright, which is more physiologic, or supine, which eliminates the force of gravity and potentially may pick up more subtle defects. The major parameter measured is total esophageal transit time, calculated from time point of entry of radioactivity into the esophagus until <10 percent of radioactivity remains in the esophagus. The test is easy to perform, quick, and usually tolerable for patients.

When the technology first emerged, many proposed esophageal scintigraphy as a useful screening test for esophageal dysmotility. One study measured esophageal scintigraphy and conventional manometry in 16 controls and 34 patients with established esophageal motility disorders.⁶ An abnormal study was defined as prolonged esophageal transit greater than 15 seconds. Results were significant for lack of false negative scintigraphy results and a 96 percent agreement between conventional manometry and scintigraphy. All patients with disorders of peristalsis due to achalasia, scleroderma, and DES had an abnormal scintigraphy. Of note, only two of ten patients with esophagitis had a prolonged esophageal transit time, making scintigraphy a poor test for reflux disease.⁶ In contrast to the results of some earlier studies, a more recent study found a greater number of false negatives using scintigraphy.⁷ Radionuclide studies were performed on 49 patients with established esophageal dysmotility disorders and 14 controls. Although esophageal transit was prolonged in the patients with achalasia, DES, and nonspecific peristaltic disorders, only a minority of the patients with nutcracker esophagus and hypertensive LES had a prolonged esophageal transit time. This led the group to conclude that scintigraphy is useful in disorders with abnormal peristalsis but a poor study in motility disorders or cases where peristalsis is preserved.⁷

The main limitation of esophageal scintigraphy is the limited number of swallows evaluated. As some motility disorders are intermittent, they could be missed by this test. This has led some groups to advise repeat scintigraphy in those patients with a high clinical suspicion for disease.⁶ Another limitation is that the presence of a hiatal hernia, particularly if a significant amount of stomach lies above the diaphragm, may be confused with distal esophagus leading to false positive results as radioactivity will persist in the hernia sac.

Esophageal Manometry

Conventional Esophageal Manometry

Esophageal manometry is performed by passing a flexible catheter transnasally down the esophagus and into the stomach. Conventional esophageal manometry relies on either a multilumen water perfusion catheter (attached to a pressure transducer) or a catheter with a few discrete solid-state pressure sensors. When the information from the pressure transducers is transmitted to the computer and analyzed, continuous pressure information from the esophagus is obtained.⁸ The channels on the catheter are usually spaced 3 to 5 cm apart for a total of six channels. Unfortunately, this constraint does not allow for the simultaneous recording of pressure spanning the entire esophagus including UES and LES. Therefore, the catheter has to be repositioned during the study to record from all points, starting in the stomach and slowly moving the catheter proximally, called the “pull-through” technique. Not all patients tolerate transnasal placement of the manometry catheter, and occasionally the catheters may need to be placed endoscopically.

Data from the study are displayed on a 2-D graph. The X-axis displays time and the Y-pressure on the left. There are 6 line tracings corresponding to each channel, displayed in order from least distance from nares at the top to greatest distance from nares at the bottom, the LES (Fig. 12-1).

High-Resolution Manometry

In the last decade, major developments in manometry technology have occurred. Newer catheters have more sensors that are closely spaced together (1 cm), which adds the ability to measure pressures within the entire esophagus, simultaneously spanning pharynx to stomach.⁸ This system of monitoring pressures can allow the investigation of the full mechanics of swallow and bolus transport. Smaller segments of the esophagus not previously able to be evaluated by conventional manometry can also be analyzed.

The large volume of data acquired from the high-resolution manometry system is displayed on a 3-D color topographic map (Fig. 12-1). As in conventional manometry, the X-axis displays time. The Y-axis displays distance from nares, again with the UES at the top and LES and stomach at the bottom. Pressure is denoted by color on the Z-axis, with warmer colors denoting high pressure and bluer colors denoting low pressure. This topographic representation makes it easier to evaluate the full dynamics of peristalsis and bolus transport from UES to stomach.⁹

Although theoretically the high-resolution manometry system provides more data, it is unclear at this time whether it translates to greater clinical utility. However, it does appear to have a logistical benefit. The high-resolution manometry system is less operator dependent, as the pull-through technique is not needed. Furthermore, the study is now shorter for the patients and may be more tolerable. Finally, the high-resolution system may be beneficial in those challenging cases where manometric subtleties are found.

Uses of Esophageal Manometry

As a research tool, manometry has helped clarify the intricacies of esophageal physiology. However, its clinical value is most useful when evaluating absent, weak, or abnormal peristalsis, and abnormalities in LES pressure and relaxation. With its closely spaced sensors, high-resolution manometry can also more easily define UES function and dysfunction compared with conventional manometry, as the UES only spans 1 cm in length.⁹ Symptoms prompting manometry testing include dysphagia, reflux and regurgitation, and chest pain.

Mechanical causes of dysphagia such as strictures or rings are far more common than motility disorders of the esophagus. Thus, manometry usually follows radiographic and endoscopic inspection of the esophagus in the evaluation of dysphagia.¹⁰ Unfortunately, many manometric abnormalities can be seen in asymptomatic healthy controls, and thus it is sometimes difficult to equate findings with motor disorders. However, there are certain manometric patterns of peristalsis and disordered LES function that correlate with specific disorders that lead to dysphagia. Ineffective peristalsis or complete aperistalsis on manometry can be seen in a variety of systemic disorders such as diabetes, connective tissue diseases like scleroderma, and amyloidosis. Specific patterns of peristaltic abnormalities and LES dysfunction also help diagnose primary esophageal motility disorders such as achalasia and DES.

The use of esophageal manometry for symptoms of reflux is not as straightforward. Certainly, ineffective esophageal peristalsis can be seen in patients with GERD; however, this is neither sensitive nor specific for GERD. Reduced LES pressure seen on manometry can contribute to an impaired antireflux barrier leading to GERD. However, the manometry study may be too short to pick up the TLESRs that are fundamental to the pathophysiology of GERD. Further discussion of reflux testing is described below.

Preoperative manometry for antireflux surgery is important for ruling out motility disorders in which antireflux surgery would be detrimental. Specifically, fundoplication in a patient with scleroderma, achalasia, or DES could worsen their symptoms. Postoperative manometry can be used in the evaluation of recurrent dysphagia after the fundoplication once mechanical obstruction is ruled out.

Use of preoperative manometry in prognostic determination of response to surgical treatment for GERD is more controversial. Some nonrandomized studies found that preoperative peristaltic dysfunction could lead to postoperative dysphagia with a classic 360 degree Nissen fundoplication. One group used a laparoscopic Toupet fundoplication in patients with peristaltic dysfunction on manometry and found lower rates of postoperative dysphagia compared with those with esophageal dysmotility who had a Nissen fundoplication.¹¹ However, a more recent randomized prospective study found no correlation between preoperative esophageal dysmotility on manometry and postoperative dysphagia in either a Nissen or a Toupet fundoplication.¹² Therefore, there is no consensus how to optimally use preoperative manometry in reflux patients.

Chest pain of esophageal origin may be due to esophageal hypersensitivity from chemical irritants, distention, or muscular contractions. Therefore, noncardiac chest pain can be due to GERD or primary motility disorders like achalasia, DES, and nutcracker esophagus. As GERD is the most common cause of esophageal chest pain, manometry would not be a high-yield study for those limitations described above. Therefore, manometry in the evaluation of chest pain usually follows thorough investigation and treatment of GERD.¹⁰

Aside from diagnosis, manometry can be used in the management of some of these disorders. There are emerging data that suggest that high-resolution manometric subtypes of achalasia may have different responses to treatment, and high-resolution manometry in these patients may have prognostic information.¹³ Manometry can also identify residual high GE junction pressures that may be amenable to further therapy in those patients with recurrent dysphagia following endoscopic or surgical therapy for achalasia.

Esophageal Reflux Testing

Catheter-Based pH Testing

Ambulatory pH monitoring is used for diagnosis of GERD, evaluation of treatment failure, and preoperative evaluation. The test involves placement of a transnasal catheter 5 cm above the LES. Patients are instructed to continue daily activities and diet. A 24-hour test will record pH events, with acid reflux events defined as a pH <4.0 for 5 or more seconds. Patients also employ event buttons to record meals, postural changes, and symptoms. The most important recorded measurements include percentage of time when pH <4, percent of upright time when pH <4, percent of supine time when pH <4, number of reflux episodes, number of reflux episodes >5 minutes, and the longest reflux episode. Using these six parameters, the DeMeester score is calculated to estimate global acid exposure. The sensitivity and specificity of ambulatory pH catheter testing for GERD reach 77 to 100 percent and 85 to 100 percent, respectively, in patients with endoscopically proven esophagitis. However, the sensitivity of pH testing ranges from 0 to 71 percent in endoscopy-negative reflux disease (NERD).¹⁴

Wireless Capsule pH Testing

Now available is a wireless pH recording capsule, the Bravo system (Medtronic, Minneapolis, MN, USA). This system was devised to avoid the limitation of patient intolerance of the transnasal catheter pH testing. The capsule is attached to the esophageal mucosa using a flexible introducer, positioned 6 cm above the GE junction as determined by endoscopy or esophageal manometry. pH data are recorded onto an external receiver by radio telemetry. The wireless system is equivalent to the catheter-based system in recording accurate pH data.¹⁵ The capsule naturally falls off several days after placement. The advantage of the wireless system is better patient tolerability. Patients are more likely to go about their normal routines including diet and exertion, which may avoid false negative results. Furthermore, increased tolerability may translate to extension of study time. Forty-eight hours of data increase the diagnostic accuracy for GERD. Disadvantages include greater cost of the test and the rare risk of chest pain requiring endoscopic removal of the capsule.¹⁴

Impedance Testing

Broadly defined, GERD is the exposure of the esophagus to gastric contents causing symptoms. Wireless and catheter-based ambulatory pH monitoring can measure the acidity of the refluxate but does not evaluate weakly acidic or nonacidic reflux events, which may still cause symptoms. Thus, a system was devised to detect all types of liquid movement in the esophagus using intraluminal electrical impedance. Intraluminal impedance monitoring uses a cylindrical catheter-containing multiple metallic electrodes. It is passed transnasally and swallowed by the patient to be placed within the esophagus above the GE junction.

The principle behind measurement of impedance is that the current flow between two electrodes will depend upon the conductivity of the surrounding environment. A liquid bolus has high electrical conductivity, and thus the resistance (or impedance) between the two electrodes will drop. On the other hand, an air bolus has low conductivity and impedance will increase. The sequence of impendence changes between the different segments of electrodes can establish directionality to determine whether the flow is related to swallowed material or esophageal reflux.¹⁶

Impedance is measured with at least three electrodes spaced 2 cm apart. The placement of the most distal electrode should be 1 to 2 cm above the LES. A number of studies have evaluated gas, liquid, and acid reflux in animals, asymptomatic controls, and patients with reflux using impedance monitoring compared with fluoroscopic exam, manometry, and pH monitoring. The sensitivity for detecting reflux using impedance ranged from 92 to 99 percent.^16–18 Therefore, the technical recommendations from a workshop led by 11 GERD specialists advise that appropriate electrode placement should detect at least 90 percent of reflux events.¹⁶ Sensitivity may be affected by conditions that lead to low baseline impedance values. Esophagitis and Barrett’s esophagus (BE) are two such conditions; therefore, it is important to be aware of these entities prior to analysis of impedance studies.

Impedance monitoring is often combined with pH monitoring to increase diagnostic accuracy and determine the specific type of reflux causing symptoms. One study measured pH and impedance events in 60 patients with heartburn or regurgitation and established the statistical relationship between symptoms and reflux events. The combination of impedance and pH yielded a higher proportion of patients with a positive symptom association probability (SAP) compared with either test alone.¹⁹