| disease | Gastroesophageal Reflux Disease (GERD) |
| alias | Gastroesophageal Reflux Disease (GERD), Reflux Esophagitis |
Reflux esophagitis refers to the inflammation, erosion, ulceration, and fibrosis of the esophageal mucosa caused by the reflux of gastric and/or duodenal contents into the esophagus. It is a type of gastroesophageal reflux disease (GERD).
bubble_chart Pathogenesis
24-hour esophageal pH monitoring has found that the normal population experiences gastro-esophageal reflux (GER), but without any clinical symptoms, hence it is referred to as physiological GER. Its characteristics are: it often occurs during the day and is rare at night; reflux is more common during or after meals; the total reflux time is less than one hour per 24 hours. Under the following conditions, physiological GER can turn into pathological GER, and even develop into reflux esophagitis.
(1) The destruction of the anatomical and physiological anti-reflux barrier at the esophagogastric junction. The anti-reflux barrier at the esophagogastric junction is also known as the first anti-reflux screen, the most important structure of which is the lower esophageal sphincter (LES). The LES is a high-pressure zone located 3 to 5 cm above the junction of the esophagus and stomach. The resting pressure here is about 2.0 to 4.0 kPa (15 to 30 mmHg), forming a pressure barrier that serves to prevent the reflux of gastric contents into the esophagus. In normal individuals, an increase in intra-abdominal pressure can cause the LES to contract reflexively through the vagus nerve, doubling the LES pressure to prevent GER. If the LES pressure is too low and an increase in intra-abdominal pressure does not cause a strong LES contraction, it can lead to GER. Studies have shown that when LESD is less than 0.8 kPa, reflux is very likely to occur, and about 17 to 39% of reflux esophagitis cases are related to this. Cholinergic and β-adrenergic agonists, α-adrenergic antagonists, dopamine, diazepam, calcium receptor antagonists, morphine, as well as dietary factors such as fat, alcohol, coffee beans, and smoking can all affect LES function and induce GER. In addition, during pregnancy, oral progesterone-containing contraceptives, and the late stage of the menstrual cycle [third stage], plasma progesterone levels increase, and the incidence of GER also increases accordingly.
(2) Impairment of esophageal acid clearance function. Normal esophageal acid clearance function includes esophageal emptying and saliva neutralization. When acidic gastric contents reflux, only 1 to 2 secondary peristaltic movements of the esophagus (about 10 to 15 seconds) are needed to empty almost all the refluxed material. The small amount of acid remaining in the esophageal mucosal crypts can be neutralized by saliva (normal individuals have about 1000 to 1500 ml of saliva with a pH of 6 to 8 passing through the esophagus into the stomach per hour). The function of esophageal acid clearance is to reduce the time the esophageal mucosa is exposed to gastric acid, thus preventing reflux esophagitis. Studies have found that most esophageal emptying abnormalities occur earlier than esophagitis, while esophagitis caused by reduced saliva secretion is rare. During nighttime sleep, saliva secretion almost stops, and secondary peristalsis of the esophagus is also rare, leading to a significant delay in esophageal acid clearance during the night, making nighttime GER more harmful.(3) Damage to the anti-reflux barrier function of the esophageal mucosa. The anti-reflux barrier function of the esophageal mucosa is composed of the following factors: ① pre-epithelial factors including the mucus layer and the concentration of HCO-3 on the mucosal surface; ② epithelial factors including the epithelial cell membrane and intercellular junction structures, as well as epithelial transport, intracellular buffer, and cell metabolism functions; ③ post-epithelial factors refer to the tissue's basal acid state and blood supply. When these defense barriers are injured, even under normal reflux conditions, esophagitis can occur. Studies have found that the weakening of esophageal epithelial cell proliferation and repair ability is one of the important reasons for the development of reflux esophagitis.
1. Abnormal gastric emptying. In patients with reflux esophagitis, the incidence of delayed gastric emptying is over 40%, but the causal relationship between the two is still debated.
2. Gastroduodenal Reflux Under normal circumstances, the squamous epithelial cells of the esophagus have a keratinized surface layer that prevents H+ from penetrating the mucous membrane, thereby protecting the esophageal mucosa from injury caused by acidic reflux. When the tone of the pyloric sphincter and the LES pressure are both low, hydrochloric acid and pepsin from the gastric juice, as well as bile acids, pancreatic juice, and lysolecithin from the duodenal fluid, can reflux into the esophagus simultaneously, eroding the keratinized layer of the esophageal epithelial cells and causing it to thin or shed. The H+ and pepsin in the refluxate then penetrate through the newly formed squamous epithelial cell layer and infiltrate the esophageal tissue, leading to esophagitis.
Therefore, reflux esophagitis is usually the result of the combined action of refluxed bile and gastric acid on the esophageal mucosa. Before bile can cause esophageal injury, there must first be dysfunction of the pylorus and LES. Patients with reflux esophagitis often have gastritis. Sliding hiatal hernia often leads to dysfunction of the LES and pylorus, making it prone to complicate this disease. Duodenal ulcers are often accompanied by high gastric acid secretion, which can easily lead to antral spasm and pyloric dysfunction, hence they are also more likely to complicate this disease. Obesity, large amounts of ascites, late-stage pregnancy (third trimester), and increased intragastric pressure can all induce this disease.
The esophageal mucosa is visibly bleeding, edematous, fragile, and prone to bleeding. In acute esophagitis, the mucosal epithelium undergoes necrosis and sloughing, leading to erosion and superficial ulcers. In severe cases, the entire epithelial layer may slough off, but it generally does not extend beyond the muscularis mucosae. In chronic esophagitis, fibrosis may develop after mucosal erosion and can extend beyond the muscularis mucosae to involve the entire esophageal wall. Repeated formation of esophageal mucosal erosions, ulcers, and fibrosis can lead to cicatricial stenosis of the esophagus. Microscopically, hyperplasia of the basal cells of the squamous epithelium is observed, with papillae extending to the surface layer of the epithelium, accompanied by vascular proliferation and infiltration of neutrophils in the lamina propria. In cases of esophageal stenosis, scarring may form in the submucosa or muscular layer. In severe esophagitis, the basal layer of the mucosal epithelium is destroyed, and due to the large size of the ulcer, the squamous epithelial cells at the ulcer margin cannot repair the ulcer through re-epithelialization, leading to metaplasia of the squamous epithelium, known as Barrett's esophagus. Ulcers occurring in Barrett's epithelium are referred to as Barrett's ulcers.
bubble_chart Clinical Manifestations
(1) Substernal burning sensation or pain is the main symptom of this disease. The symptoms usually occur about 1 hour after eating and can be induced by semi-recumbent position, forward bending of the body, or strenuous exercise. They often disappear after taking antacids, but can be aggravated by overheated or overly acidic foods. In patients with achlorhydria, the burning sensation is mainly caused by bile reflux, and the effect of taking antacids is not significant. The severity of the burning sensation does not necessarily correspond to the severity of the lesion. Severe esophagitis, especially with scar formation, may have no or only mild burning sensation.
(2) Gastroesophageal reflux often occurs after meals, when bending forward, or during nighttime sleep, when acidic liquid or food refluxes from the stomach and esophagus to the pharynx or mouth. This symptom often appears before the substernal burning sensation or burning pain.
(3) Dysphagia in the initial stage [first stage] can often be caused by secondary esophageal spasm due to esophagitis, presenting as intermittent dysphagia. In the late stage [third stage], due to esophageal scar formation and narrowing, the burning sensation and burning pain gradually decrease and are replaced by permanent dysphagia. Eating solid food may cause a feeling of obstruction or pain at the xiphoid process.
(4) Bleeding and anemia Severe esophagitis can lead to esophageal mucosal erosion and bleeding, mostly chronic and small in amount. Long-term or massive bleeding can lead to iron-deficiency anemia.
bubble_chart Auxiliary Examination
(1) Esophageal Acid Perfusion Test (Acid Perfusion Test) The patient is seated, and a nasogastric tube is inserted through the nasal cavity. When the tube reaches 30-35 cm, physiological saline is first dripped at a rate of about 10 ml per minute for 15 minutes. If the patient experiences no significant discomfort, 0.1N hydrochloric acid is then dripped at the same rate for 30 minutes. A positive reaction is indicated by the onset of retrosternal pain or a burning sensation during the acid perfusion, typically within the first 15 minutes. If a positive reaction occurs twice and can be alleviated by dripping physiological saline, acid GER can be diagnosed. The sensitivity and specificity of the test are approximately 80%.
(2) Intraesophageal pH Measurement A pH electrode is gradually pulled into the esophagus and placed about 5 cm above the LES. Normally, the gastric pH is very low. The patient is then instructed to lie supine and perform actions that increase abdominal pressure, such as closing the mouth, pinching the nose, deep exhalation, or bending the legs, and forcefully blowing the nose 3-4 times. If the esophageal pH drops below 4, it indicates the presence of GER. Alternatively, 300 ml of 0.1N hydrochloric acid can be injected into the gastric cavity. Before and 15 minutes after the injection, the patient is instructed to lie supine and perform actions that increase abdominal pressure. In cases of GER, the esophageal pH will significantly decrease after the injection of hydrochloric acid. In recent years, 24-hour esophageal pH monitoring has become the standard for detecting acidic GER. The measurements include the percentage of time with esophageal pH < 4, the percentage of time with pH < 4 in the supine and upright positions, the number of times pH < 4 occurs, the number of times pH < 4 lasts for more than 5 minutes, and the longest duration of pH < 4. In China, normal 24-hour esophageal pH monitoring shows that the time with pH < 4 is below 6%, the number of times it lasts for more than 5 minutes is ≤ 3, and the longest reflux duration is 18 minutes. These parameters help determine the presence of acid reflux and elucidate the relationship between chest pain, pulmonary diseases, and acid reflux.
(3) Intraesophageal Pressure Measurement This is typically performed using a continuous perfusion catheter system filled with water to estimate the function of the LES and esophagus. During the measurement, the pressure catheter is first inserted into the stomach and then withdrawn at a speed of 0.5-1.0 cm/min while measuring the intraesophageal pressure. Normally, the resting LES pressure is about 2-4 kPa (15-30 mmHg), or the ratio of LES pressure to intragastric pressure is > 1. If the resting LES pressure is < 0.8 kPa (6 mmHg) or the ratio is < 1, it suggests LES dysfunction or the presence of GER.
(4) Gastroesophageal Scintigraphy This method estimates the volume of gastroesophageal reflux. The patient fasts and drinks 300 ml of an acidified orange juice solution containing 300 μCi 99m Tc-Sc (containing 150 ml of orange juice and 150 ml of 0.1N HCl), followed by 15-30 ml of cold water to clear any residual solution in the esophagus, and then undergoes imaging in an upright position. Normally, no radioactivity is present above the stomach after 10-15 minutes. Otherwise, it indicates the presence of GER. The sensitivity and specificity of this method are approximately 90%.
(5) Barium Swallow X-ray Examination This method is less sensitive and has a higher rate of false negatives.
(6) Endoscopy and Biopsy Pathological Examination Through endoscopy and biopsy pathological examination, it is possible to determine whether there are pathological changes of reflux esophagitis, as well as the presence of gall fel reflux. This examination is of significant value in assessing the severity of pathological changes in reflux esophagitis. According to the Savary and Miller classification criteria, the inflammatory lesions of reflux esophagitis can be divided into 4 grades: Grade I is characterized by single or several non-confluent sexually transmitted disease changes, presenting as erythema or superficial erosion; Grade II involves confluent sexually transmitted disease changes, but not diffuse or circumferential; Grade III lesions are diffuse and circumferential, with erosions but no stricture; Grade IV shows chronic sexually transmitted disease changes, presenting as ulcers, strictures, fibrosis, esophageal shortening, and Barrett's esophagus.
A burning sensation or burning pain behind the sternum can be evaluated through intraesophageal pH monitoring, esophageal manometry, and gastroesophageal scintigraphy to determine the presence of GER. The esophageal acid perfusion test can be used to confirm whether the symptoms are caused by GER. If necessary, esophageal endoscopy and biopsy can be performed to establish a definitive diagnosis.
Reflux esophagitis should be differentiated from conditions such as peptic ulcer, colicky pain, esophageal cancer, and esophageal fungal infections.
bubble_chart Treatment Measures
(1) General Treatment Diet should be small and frequent meals, not overeating; avoid tobacco, alcohol, coffee beans, chocolate, acidic foods, and excessive fat; avoid lying down immediately after meals; elevate the head of the bed by 20-30cm when lying down, do not tighten the belt too much, and avoid any conditions that increase abdominal pressure.
(2) Promoting Esophageal and Gastric Emptying
1. Dopamine Antagonists These drugs can promote esophageal and gastric emptying and increase LES tension. These drugs include metoclopramide (Metoclopramide, Gastric Relief) and domperidone (Domperidone, Motilium), both at 10-20mg, 3-4 times daily, taken before bedtime and meals. The former, if the dose is too large or taken long-term, may cause extrapyramidal symptoms, so it should be used with caution in elderly patients; the latter, if taken long-term, may also cause hyperprolactinemia, leading to adverse reactions such as breast hyperplasia, lactation, and amenorrhea.
2. Cisapride (Cisapride) Promotes esophageal and gastric motility and emptying by releasing acetylcholine from postganglionic neurons in the myenteric plexus, thereby reducing gastroesophageal reflux. 10-20mg, 3-4 times daily, with almost no adverse reactions.
3. Cholinergic Drugs Bethanechol (Bethanechol) can increase LES tension, promote esophageal contraction, and accelerate the emptying of acidic contents in the esophagus to improve symptoms, 25mg each time, 3-4 times daily. This drug can stimulate gastric acid secretion, so long-term use should be cautious.
(3) Reducing Gastric Acid ① Antacids Can neutralize gastric acid, thereby reducing the activity of gastric protease and decreasing the injury of acidic gastric contents to the esophageal mucosa. Alkaline drugs themselves also have the effect of increasing LES tension. Aluminum hydroxide gel 10-30ml and magnesium oxide 0.3g, 3-4 times daily. Alginate foam (Gaviscon, Alginate) contains alginic acid, sodium alginate, and antacids, which can float on the surface of gastric contents and prevent reflux of gastric contents. ② Histamine H2 Receptor Antagonists Cimetidine (Cimetidine), Ranitidine (Ranitidine), and Famotidine (Famotidine) can be selected, with doses of 200mg, 3-4 times daily; 150mg, twice daily; and 30mg daily, respectively. The treatment course is 6-8 weeks. These drugs can strongly inhibit gastric acid secretion and improve gastroesophageal acid reflux. If the above symptoms do not improve, the dose can be increased to 2-3 times. ③ Proton Pump Inhibitors These drugs can block the H+-K+-ATPase of parietal cells. Omeprazole (Omeprazole) and Lansoprazole (Lansoprazole) have been widely used in clinical practice, with the former at 20mg daily and the latter at 30mg daily, which can improve symptoms.
(4) Combination Therapy The combination of drugs promoting esophageal and gastric emptying and antacids has a synergistic effect, promoting the healing of esophagitis. Dopamine antagonists or cisapride can also be combined with histamine H2 receptor antagonists or proton pump inhibitors.
After the condition improves and medication is stopped, since the LES tension has not been fundamentally improved, about 80% of cases relapse within 6 months. If one of the histamine H2 receptor antagonists, proton pump inhibitors, or dopamine antagonists is selected for maintenance therapy, or medication is promptly used when symptoms recur, better efficacy can be achieved.
(5) Surgical Treatment Mainly applicable to esophageal scar stenosis (which can be treated with dilation or surgical correction) and cases where medical treatment is ineffective, with recurrent bleeding, recurrent pneumonia, etc. {|112|}
In addition to causing complications such as esophageal stricture, bleeding, and ulcers, the reflux of gastric fluid can also erode the pharynx, vocal cords, and trachea, leading to chronic pharyngitis, chronic laryngitis, and tracheitis, clinically referred to as Delahunty syndrome. The reflux and aspiration of gastric fluid into the respiratory tract can also result in aspiration pneumonia. Recent studies have shown that GER is associated with some cases of recurrent asthma, cough, nocturnal apnea, and chest pain resembling colicky pain.
