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Author: Laurence Scott Bailen, M.D.
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1. Objectives: Pathophysiology of the Esophagus

  1. Understand normal esophageal anatomy and physiology

  2. Understand the importance of the LES in the pathophysiology of gastroesophageal reflux

  3. Understand what factors alter the LES pressure

  4. Understand the components of the LES barrier

  5. Understand symptoms of esophageal disease: dysphagia, odynophagia, heartburn

  6. To be able to understand esophageal disorders, particularly reflux esophagitis, Barrett’s esophagus, and achalasia

2. Anatomy and Physiology

2.1. Motor Function

  1. The esophagus is a hollow tubular organ, consisting of three components: the upper esophageal sphincter (UES), the esophageal body and the lower esophageal sphincter (LES).

  2. The oral cavity, pharynx, larynx and the components of the esophagus are involved in:

    1. The task of transferring food from the pharynx to the stomach.

    2. Between swallowing, the components of the esophagus prevent the retrograde flow of esophageal and gastric contents.

2.2. Components of Esophagus

2.2.1. Upper Esophageal Sphincter (UES)

  1. It is an area of high pressure ~ 100 mm Hg, consisting of striated muscle that is 2 to 4.5 cm long.

  2. It is formed primarily by the horizontal fibers of cricopharyngeus muscle and the inferior pharyngeal constrictor muscle.

  3. It receives motor input from the brain stem (nucleus ambiguous) and is tonically closed, thus preventing air from entering the esophagus and aspiration of gastroesophageal contents.

2.2.2. Esophageal Body

  1. It consists of an empty tube, approximately 20 cm long, comprised of two layers of muscle: an inner circular layer and an outer longitudinal layer.

  2. The upper 1/3 portion of the esophagus is primarily striated muscle.

  3. The lower 2/3 of the esophagus, along with the LES, is entirely smooth muscle.

  4. The nerve networks for the esophageal body lie between the muscular layers.

    1. Meissner's (submucosa) plexus is between the muscularis mucosa and the circular muscle layer.

    2. Auerbach's (myenteric) plexus is between the circular and longitudinal muscle layers.

    3. Innervation of the smooth muscle and LES is primarily via the vagus nerve from neurons arising in the dorsal motor nucleus of the brain stem and the nerve endings in the myenteric plexus.

2.2.3. Lower Esophageal Sphincter (LES)

  1. The LES is a 2 cm to 4.5 cm long, high pressure zone of smooth muscle. At rest, the sphincter is tonically contracted with normal pressure ranging from 10 mm to 45 mm Hg.

  2. On swallowing, the LES relaxes promptly in response to the initial neural discharge from the swallowing center. During relaxation, the pressure falls approximately to the level of gastric pressure.

  3. The LES serves two functions: 1) prevents gastroesophageal reflux 2) relaxes with swallowing, allowing movement of ingested material into the stomach.

  4. The tonic contractions of LES are predominantly due to intrinsic muscle activity and some component of vagally mediated cholinergic control.

  5. Factors & agents affecting LES pressure:

    Decrease LES

    Increase LES

    Gastric distention, fat, nicotine, ethanol, chocolate, theophylline, caffeine, secretin, CCK, progesterone, estrogen, glucagon, VIP, dopamine, anticholinergics, alphaadrenergic antagonists

    Proteins, gastrin, motilin, pancreatic polypeptide, substance P, bombesion

3. Integrated Functions

  1. Swallowing is initiated by combination of conscious and subconscious cues regulated through the swallowing center in the medulla.

  2. Swallowing has been divided into three stages. One complete swallow requires 1.0 seconds.

    1. Oral stage (voluntary):
      This stage is largely voluntary, involving chewing of food and forming it into an oral bolus.

    2. Pharyngeal stage (involuntary):

      1. This stage is involuntary and requires the finetuned coordinated sequence of contraction and relaxation, resulting in transfer of the ingested material from the pharynx to the esophagus.

      2. This is a complex event comprising CNS reflex response and pharyngeal muscles.

      3. During this time, respiration is interrupted, and the airway is protected by contraction of the vocal cords and the epiglottis.

      4. Once a bolus of food is propelled by the tongue through the hypopharynx, the UES relaxes in time to accept the bolus.

    3. Esophageal stage:

      1. This stage allows the transport of ingested material from the mouth to the stomach.

      2. Peristalsis is formed by contraction of both longitudinal and circular muscles of the esophagus.

      3. A primary peristaltic wave starts in the upper body of the esophagus and is initiated by a swallow of food.

      4. If part of the bolus remains in the esophagus, a secondary peristaltic wave begins just above it and sweeps it through the LES in response to local luminal distention.

4. Antireflux Barrier

  1. The LES, crural diaphragm, and phrenoesophageal ligament are the anatomic structures defining the antireflux barrier for gastric contents.

  2. Three important LES mechanisms for gastroesophageal reflux have been identified:

    1. Weak basal LES pressure

    2. Inadequate LES response to increased abdominal pressure

    3. Transient relaxation of LES

      1. Both primary and secondary esophageal peristalsis are accompanied by relaxation of the LES, thus allowing esophageal contents to be transferred to the stomach.

      2. Transient complete relaxation of the LES without peristalsis has been identified as an important cause of reflux of gastric contents into the esophagus.

5. Symptoms of Esophageal Disease

  1. Dysphagia :

    1. A specific term referring to the subjective sensation of food being stuck as it passes from the mouth towards the stomach.

    2. This may be due to 1) neuromuscular dysfunction, 2) obstructing lesion in the esophagus, or 3) an inflammatory process in the esophagus.

  2. Odynophagia :

    1. Refers to the sensation of pain distinctly associated with the act of swallowing.

    2. This is most commonly a sharp pain.

    3. Odynophagia is usually associated with a disorder causing diffuse and severe inflammation of the esophageal mucosa.

    4. Patients experiencing only pain with swallowing and no sensation of obstruction do not have true dysphagia but rather odynophagia.

  3. Pyrosis or Heartburn :

    1. The most common symptom related to the esophagus and typically refers to burninglike pain that radiates from the epigastrium.

    2. Pyrosis is usually a primary symptom of gastroesophageal reflux disease.

  4. Chest Pain :

    1. Chest pain arising from the esophagus as a result of motility abnormalities may closely mimic that of coronary artery disease.

  5. Regurgitation :

    1. Refers to the sudden, effortless return of small volumes of gastric or esophageal contents into the pharynx.

6. Diagnostic Procedures

  1. Barium swallow :

    1. Radiographic evaluation of the esophagus is performed by having the patient take 5 to 10 single swallows of barium.

    2. This is usually the initial examination of patients presenting with dysphagia.

  2. Esophageal manometry :

    1. Manometric evaluation of the esophagus is the definitive test for diagnosing esophageal motility disorders, as it allows assessment of the lower sphincter pressure and esophageal pressure waves.

  3. pH Monitor Test :

    1. Prolonged monitoring of esophageal pH for 12 to 24 hours is the most reliable means of diagnosing acid reflux.

    2. A pH electrode is passed through the nose or mouth to 5 cm above the manometrically determined LES.

    3. An episode of acid reflux is defined when there is a decrease of esophageal pH to less than or equal to 4 (>4% of time over 24 hours).

  4. Endoscopy :

    1. Upper endoscopy (esophagogastroduodenoscopy or EGD) is the best method for identifying mucosal abnormalities of the esophagus and allows tissue samples to be obtained.

    2. Endoscopy is a preferred method for identifying esophagitis or neoplasms.

7. Motility Disorders of Esophagus

  1. Achalasia:

    1. Characterized by three primary abnormalities in the function of LES and smooth muscle portion of the esophageal body:

      1. absent peristaltic activity in the esophageal body

      2. increased resting tone of the LES, and

      3. absent or incomplete relaxation of the LES with swallows. The LES does not appropriately relax, offering resistance to the flow of liquids and solids from the esophagus into the stomach.

    2. Etiology and pathophysiology: the cause remains unknown, but the major neuroanatomic changes include loss of ganglion cells within the Auerbach's plexus, degeneration of vagus nerve, and changes in the dorsal motor nucleus of the vagus. It is clinically similar to Chaga's disease, which is due to a protozoan infection, Trypanosoma cruzi (found in South America).

    3. Achalasia is characteristically a disease, which progresses slowly, with dysphagia for both liquids and solids.

  2. Diffuse esophageal spasm (DES):

    1. A rare motor disorder of the esophagus involving only the smooth muscle portion. This disorder is characterized by high amplitude, repetitive, non-peristaltic esophageal contractions and is often associated with chest pain.

    2. DES is distinguished from achalasia by the normal function of the LES as well as by the intermittent presence of normal peristaltic sequences.

  3. Scleroderma:

    1. A multi-system disorder characterized by fibrosis involving the skin and multiple organs.

    2. Esophageal abnormality is based on patchy smooth muscle atrophy with fibrosis, which accounts for the decreased esophageal contractility and absence of resting LES tone.

    3. As the LES becomes incompetent, reflux of gastric acid may damage the lower esophagus. Treatment: agents, which lower the acidity of gastric secretions and dilations for strictures.

8. Other Disorders of the Esophagus

  1. Hiatus hernia:

    1. Defined as a herniation of part of the stomach through the esophageal hiatus in the diaphragm and into the chest, and may be sliding or paraesophageal.

    2. The presence of hiatus hernia will not itself lead to reflux.

  2. Rings and webs:
    Rings and webs are thin projections of mucosa upon the lumen of the esophagus. Mucosal rings and webs can cause mechanical obstruction of the esophageal lumen with dysphagia.

    1. Schatzki ring, B ring, or lower mucosal esophageal ring

      1. Refers to a mucosal projection that involves the most distal esophagus.

      2. Often referred to as "steakhouse syndrome" and may present with non-progressive dysphagia for solids.

      3. Usually has squamous mucosa lining its proximal surface and gastric columnar mucosa lining its distal side, and is located above the diaphragm

    2. Webs are usually found in the upper esophagus but could be found elsewhere.

  3. Carcinoma:

    1. Squamous cell carcinoma and adenocarcinoma are the two most common types of esophageal cancer.

    2. Recently, the incidence of adenocarcinoma has been increasing.

    3. Symptoms include progressive dysphagia resulting in weight loss.

  4. Reflux esophagitis and peptic strictures:

    1. Reflux esophagitis refers to esophageal injury that is due to reflux of acidic gastric contents into the esophagus.

    2. Peptic stricture represents the end stage of ongoing reflux, mucosal damage, and healing. The stricture itself is probably a combination of fibrosis, spasm, and edema. Strictures present with slowly progressive dysphagia for solids.

  5. Barrett's esophagus:

    1. This is defined as a patch or patches of metaplastic columnar epithelium (specialized intestinal metaplasia) in the lower esophagus, often due to severe reflux esophagitis.

    2. Diagnosis is made by endoscopy and confirmed by biopsy.

    3. The major concern is that it is associated with increased prevalence and incidence of adenocarcinoma of the distal esophagus.

    4. The prevalence rate is estimated at 10%, a 3040 fold increase over the general population.

  6. Pillinduced esophagitis:

    1. A variety of medications taken in pill form are capable of resulting in caustic injury if they linger in the esophagus.

    2. Some agents include potassium chloride tablets, ferrous sulfate, quinidine, nonsteroidal antiinflammatory agents, and tetracycline.

  7. Infectious esophagitis:

    1. The agents most often responsible for important esophageal infections include candidiasis, herpes simplex virus, and cytomegalovirus.

    2. These infections are seen most frequently immunocompromised patients (i.e. AIDS, malignancy, or immunosuppressive agents.)