Pathophysiology of Gastrointestinal Tract: Esophagus

1. Pathophysiology of Gastrointestinal Tract 1:Esophagus By: Amir A. Ashrafian, MD. D:\Photos\Voyage\North1204\Road

2. Goals: learning 1. Esophageal Structure and Function 2. Symptoms of Esophageal Disease 3. Esophageal Disorders: Structural Disorders Hiatal Hernia Rings and Webs Diverticula Tumors Esophageal Motility Disorders Achalasia Diffuse Esophageal Spasm (Des) Gastroesophageal Reflux Disease (GERD) Pathophysiology Symptoms Complications Treatment Congenital Anomalies

3. Introduction: Gastrointestinal tract Function GIT serves two functions—assimilating nutrients and eliminating waste. Mouth: Chewing & Mixing with salivary amylase Esophagus propels the bolus into the stomach. The esophageal mucosa squamous, does not permit significant diffusion or absorption. Stomach mixing the bolus with pepsin and acid. Gastric acid sterilizes the upper gut. Proximal stomach has a storage function. Distal stomach exhibits phasic contractions that propel solid food residue against the pylorus. Stomach secretes intrinsic factor for vitamin B12 absorption. The small intestine serves most of the nutrient absorptive function of the gut. The intestinal mucosa exhibits villus architecture to provide maximal surface area for absorption and is endowed with specialized enzymes and transporters.

4. Introduction: Gastrointestinal tract Function Triturated food from the stomach mixes with pancreatic juice and bile in the duodenum to facilitate digestion. Pancreatic juice contains the main enzymes for carbohydrate, protein, and fat digestion as well as bicarbonate to optimize the pH for activation of these enzymes. Bile secreted by the liver and stored in the gallbladder is essential for intestinal lipid digestion. The proximal intestine is optimized for rapid absorption of nutrient breakdown products and most minerals, while the ileum is better suited for absorption of vitamin B12 and bile acids. The small intestine also aids in waste elimination. The small intestine terminates in the ileocecal junction, a sphincteric structure that prevents coloileal reflux and maintains small-intestinal sterility.

5. Introduction: Gastrointestinal tract Function The colonic mucosa dehydrates the stool, decreasing daily fecal volumes from 1000–1500 mL delivered from the ileum to 100–200 mL expelled from the rectum. The colonic lumen possesses a dense bacterial colonization that ferments undigested carbohydrates and short-chain fatty acids. Whereas transit times in the esophagus are on the order of seconds and times in the stomach and small intestine range from minutes to a few hours, propagation through the colon takes more than one day in most individuals. The proximal colon serves to mix and absorb fluid, while the distal colon exhibits peristaltic contractions and mass actions that function to expel the stool. The colon terminates in the anus.

6. Esophageal Structure and Function The esophagus is a hollow muscular tube coursing through the posterior mediastinum joining the hypopharynx to the stomach with a sphincter at each end. It functions to transport food and fluid between these ends, otherwise remaining empty. Esophageal diseases can be manifested by impaired function or pain. Key functional impairments are swallowing disorders and excessive gastroesophageal reflux. Pain, sometimes indistinguishable from cardiac chest pain, can result from inflammation, infection, dysmotility, or neoplasm.

7. Symptoms of Esophageal Disease The clinical history remains central to the evaluation of esophageal symptoms. Important details include weight gain or loss, gastrointestinal bleeding, dietary habits including the timing of meals, smoking, and alcohol consumption. The major esophageal symptoms are heartburn, regurgitation, chest pain, dysphagia, odynophagia, and globus sensation. Heartburn (pyrosis), the most common esophageal symptom, is characterized by a discomfort or burning sensation behind the sternum that arises from the epigastrium and may radiate toward the neck. Heartburn is an intermittent symptom, most commonly experienced after eating, during exercise, and while lying recumbent. The discomfort is relieved with drinking water or antacid but can occur frequently and interfere with normal activities including sleep. Regurgitationis the effortless return of food or fluid into the pharynx without nausea or retching. Patients report a sour or burning fluid in the throat or mouth that may also contain undigested food particles. Bending, belching, or maneuvers that increase intraabdominal pressure can provoke regurgitation.

9. Symptoms of Esophageal Disease Chest painis a common esophageal symptom with characteristics similar to cardiac pain, sometimes making this distinction difficult. Esophageal pain is usually experienced as a pressure type sensation in the mid chest, radiating to the mid back, arms, or jaws. The similarity to cardiac pain is likely because the two organs share a nerve plexus and the nerve endings in the esophageal wall have poor discriminative ability among stimuli. Gastroesophageal reflux is the most common cause of esophageal chest pain. Esophageal dysphagia is often described as a feeling of food "sticking”. Important distinctions are between uniquely solid food dysphagia as opposed to liquid and solid, episodic versus constant dysphagia, and progressive versus static dysphagia. If the dysphagia is for liquids as well as solid food, it suggests a motility disorder such as achalasia. Conversely, uniquely solid food dysphagia is suggestive of a stricture, ring, or tumor.

10. Symptoms of Esophageal Disease Odynophagia is pain either caused by or exacerbated by swallowing. Odynophagia is more common with pill or infectious esophagitis than with reflux esophagitis and should prompt a search for these entities. When odynophagia does occur in GERD, it is likely related to an esophageal ulcer or deep erosion. Globus sensation, alternatively labeled "globus hystericus," is the perception of a lump or fullness in the throat that is felt irrespective of swallowing. Although such patients are frequently referred for an evaluation of dysphagia, globus sensation is often relieved by the act of swallowing. As implied by its alternative name (globus hystericus), globus sensation often occurs in the setting of anxiety or obsessive-compulsive disorders. Water brashis excessive salivation resulting from a vagal reflex triggered by acidification of the esophageal mucosa. This is not a common symptom.

12. Esophageal Disorders Structural Disorders Hiatal Hernia Hiatus hernia is a herniation of viscera, most commonly the stomach, into the mediastinum through the esophageal hiatus of the diaphragm. Four types of hiatus hernia are distinguished with type I, or sliding hiatal hernia comprising at least 95% of the overall total. A sliding hiatal hernia is one in which the gastroesophageal junction and gastric cardia slide upward as a result of weakening of the phrenoesophageal ligament attaching the gastroesophageal junction to the diaphragm at the hiatus. True to its name, sliding hernias enlarge with increased intraabdominal pressure, swallowing, and respiration. The incidence of sliding hernias increases with age and conceptually, results from wear and tear: increased intraabdominal pressure from abdominal obesity, pregnancy, etc., and hereditary factors predisposing to the condition. The main significance of sliding hernias is the propensity of affected individuals to have GERD.

14. Esophageal Disorders Structural Disorders Rings and Webs A lower esophageal mucosal ring, also called a B ring, is a thin membranous narrowing at the squamocolumnar mucosal junction. Its origin is unknown but B rings are demonstrable in about 15% of people and are usually asymptomatic. When the lumen diameter is less than 13 mm, distal rings are usually associated with episodic solid food dysphagia and are called Schatzki rings. Schatzki ring is one of the most common causes of intermittent food impaction. Symptomatic rings are easily treated by dilatation.

16. Esophageal Disorders Structural Disorders Diverticula Esophageal diverticula are categorized by location with the most common being epiphrenic, hypopharyngeal (Zenker's), and mid esophageal. Epiphrenic and Zenker's diverticula are false diverticula involving herniation of the mucosa and submucosa through the muscular layer of the esophagus. These lesions result from increased intraluminal pressure associated with distal obstruction. Small Zenker's diverticula are usually asymptomatic but when they enlarge sufficiently to retain food and saliva they can be associated with dysphagia, halitosis, and aspiration. Treatment is by surgical diverticulectomy. Mid-esophageal diverticula may be caused by traction from adjacent inflammation (classically tuberculosis) in which case they are true diverticula involving all layers of the esophageal wall, or by pulsion associated with esophageal motor disorders.

17. Esophageal Disorders Structural Disorders Tumors Esophageal cancer occurs in about 4.5:100,000 people in the United States with the associated mortality being only slightly less at 4.4:100,000. One notable trend is the shift of dominant esophageal cancer type from squamous cell to adenocarcinoma, strongly linked to reflux disease and Barrett's metaplasia. The typical presentation of esophageal cancer is of progressive solid food dysphagia and weight loss. Associated symptoms may include odynophagia, iron deficiency, and, with mid-esophageal tumors, hoarseness from left recurrent laryngeal nerve injury. Even when detected as a small lesion, esophageal cancer has poor survival because of the abundant esophageal lymphatics leading to regional lymph node metastases. Benign esophageal tumors are uncommon and usually discovered incidentally. In decreasing frequency of occurrence, cell types include leiomyomas, fibrovascular polyps, squamous papillomas, granular cell, lipomas, neurofibromas, and inflammatory fibroid polyps.

20. Esophageal Disorders Congenital Anomalies The most common congenital esophageal anomaly is esophageal atresia, occurring in about 1 in 5,000 live births. Esophageal atresia is usually recognized and corrected surgically within the first few days of life. Later life complications include dysphagia from anastomotic strictures or absent peristalsis and reflux, which can be severe. Less common developmental anomalies include congenital esophageal stenosis, webs, and duplications.

21. Esophageal Disorders Esophageal Motility Disorders Esophageal motility disorders are diseases attributable to esophageal neuromuscular dysfunction commonly associated with dysphagia, chest pain, or heartburn. Achalasia Achalasia is a rare disease caused by loss of ganglion cells within the esophageal myenteric plexus with a population incidence of about 1:100,000 and usually presenting between age 25 and 60. Functionally, inhibitory neurons mediate deglutitive lower esophageal sphincter (LES) relaxation and the sequential propagation of peristalsis. Their absence leads to impaired deglutitive LES relaxation and absent peristalsis.

23. Esophageal Disorders Esophageal Motility Disorders Achalasia (continued) Long-standing achalasia is characterized by progressive dilatation and sigmoid deformity of the esophagus with hypertrophy of the LES. Clinical manifestations may include dysphagia, regurgitation, chest pain, and weight loss. Most patients report solid and liquid food dysphagia. Regurgitation occurs when food, fluid, and secretions are retained in the dilated esophagus. Patients describe a squeezing, pressure-like retrosternal pain, sometimes radiating to the neck, arms, jaw, and back. Therapy is directed at reducing LES pressure so that gravity and esophageal pressurization promote esophageal emptying. Peristalsis rarely, if ever, returns.

24. Esophageal Disorders Esophageal Motility Disorders Achalasia (continued) LES pressure can be reduced by pharmacologicals therapy, forceful dilatation, or surgical myotomy. Nitrates or calcium channel blockers are administered before eating, advising caution because of their effects on blood pressure. Botulinum toxin, injected into the LES under endoscopic guidance, inhibits acetylcholine release from nerve endings and improves dysphagia in about 66% of cases for at least 6 months. The only durable therapies for achalasia are pneumatic dilatation and Heller myotomy. Pneumatic dilatation, with a reported efficacy ranging from 32–98%, is an endoscopic technique using a noncompliant, cylindrical balloon dilator positioned across the LES and inflated to a diameter of 3–4 cm.

26. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) It is estimated that 15% of adults in the United States are affected by GERD. With respect to the esophagus, the spectrum of injury includes esophagitis, stricture, Barrett's esophagus, and adenocarcinoma. Of particular concern is the rising incidence of esophageal adenocarcinoma, an epidemiologic trend that parallels the increasing incidence of GERD.

28. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) Pathophysiology The best defined subset of GERD patients, albeit a minority overall, have esophagitis. Esophagitis occurs when refluxed gastric acid and pepsin cause necrosis of the esophageal mucosa causing erosions and ulcers. Three dominant mechanisms of esophagogastric junction incompetence are recognized: (1) transient LES relaxations, (2) LES hypotension, or (3) anatomic distortion of the esophagogastric junction inclusive of hiatus hernia. Factors tending to exacerbate reflux regardless of mechanism are abdominal obesity, pregnancy, gastric hypersecretory states,and delayed gastric emptying. Inherent in the pathophysiologic model of GERD is that gastric juice is harmful to the esophageal epithelium.

29. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) Symptoms Heartburn and regurgitation are the typical symptoms of GERD. Somewhat less common are dysphagia and chest pain. With chest pain, cardiac disease must be carefully considered. Extraesophageal syndromes with an established association to GERD include chronic cough, laryngitis, asthma, and dental erosions. A multitude of other conditions including pharyngitis, chronic bronchitis, pulmonary fibrosis, chronic sinusitis, cardiac arrhythmias, sleep apnea, and recurrent aspiration pneumonia have proposed associations with GERD.

30. GERD (GORD)

31. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) Complications The complications of GERD are related to chronic esophagitis (bleeding and stricture) and the relationship between GERD and esophageal adenocarcinoma. However, both esophagitis and peptic strictures have become increasingly rare in the era of potent antisecretory medications. Conversely, the most severe histologic consequence of GERD is Barrett's metaplasia with the associated risk of esophageal adenocarcinoma, and the incidence of these lesions has increased, not decreased in the era of potent acid suppression.

32. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) Treatment Lifestyle modifications are routinely advocated as GERD therapy. Broadly speaking, these fall into three categories:(1) avoidance of foods that reduce lower esophageal sphincter pressure, making them "refluxogenic" (these commonly include fatty foods, alcohol, peppermint, tomato-based foods, possibly coffee and tea); (2) avoidance of acidic foods that are inherently irritating; and (3) adoption of behaviors to minimize reflux and/or heartburn. In general, minimal evidence supports the efficacy of these measures. However, clinical experience dictates that subsets of patients are benefitted by specific recommendations, based on their unique history and symptom profile. A patient with sleep disturbance from nighttime heartburn is likely to benefit from elevation of the head of the bed and avoidance of eating before retiring, but those recommendations are superfluous for a patient without nighttime symptoms.

34. Esophageal Disorders Gastroesophageal Reflux Disease (GERD) Treatment (continued) The most broadly applicable recommendation is for weight reduction. Even though the benefit with respect to reflux cannot be assured, the strong epidemiologic association between obesity and GERD and the secondary health gains of weight reduction are beyond dispute. The dominant pharmacologic approach to GERD management is with inhibitors of gastric acid secretion. Pharmacologically reducing the acidity of gastric juice does not prevent reflux, but it ameliorates reflux symptoms and allows esophagitis to heal. Proton pump inhibitors (PPIs) are more efficacious than histamine2 receptor antagonists (H2RAs).