Clinical GERD and esophageal mucosal damage caused by excessive exposure (or exposure) of the gastroesophageal lumen to gastric juices is called gastroesophageal reflux disease (GERD). The occurrence of GERD and its complications is multifactorial. These include defects in the anti-reflux mechanism of the esophagus itself, such as dysfunction of the lower esophageal sphincter (LES) and abnormal esophageal body movements, as well as dysfunction of many mechanical factors outside the esophagus.
Gastroesophageal reflux disease refers to the reflux of gastric contents, including bile salts and pancreatic enzymes from the duodenum into the stomach, into the esophagus, and is divided into two types: physiological and pathological. Pathological reflux is reflux that occurs due to dysfunction of the lower esophageal sphincter and/or abnormalities in the tissue structure related to its function to the extent that les pressure is low, causing a series of clinical symptoms and complications.
Low anti-reflux barrier function
①Low les pressure: Reduced les pressure is the main cause of gastroesophageal reflux. Under physiological conditions, the les reflexively relaxes when there is a swallowing action, the pressure drops, pushing food into the stomach through normal esophageal peristalsis, and then returns to normal levels, and there is a reactive pressure increase to prevent food reflux; when the intragastric and intra-abdominal pressure rises, the les will undergo reactive active contraction to make its pressure exceed the increased intragastric pressure, playing an anti-reflux role. If this normal function is disturbed by some factors, it can cause reflux of gastric contents into the esophagus.
②The role of the surrounding tissues is weakened, such as: lack of abdominal segment of the esophagus, resulting in increased intra-abdominal pressure can not transmit intra-abdominal pressure to les to contract to achieve the anti-reflux effect; small infants esophageal angle (formed by the angle between the esophagus and the gastric cardia, his angle) is large (normal 30 ° ~ 50 °); transverse septal pedicle muscle clamping effect is weakened; septal esophageal ligament and lower esophageal mucosal defense anatomical structures occur organic or The normal anti-reflux function can be disrupted by functional lesions of the septal ligament and lower esophageal mucosa. Under normal circumstances, the ability of esophageal contouring depends on the propulsive peristalsis of the esophagus, the neutralizing effect of saliva, the gravitational force of the esophagus pill and the bicarbonate secreted under the esophageal mucosa according to the GERD examination sheet, and other factors to play its role in clearing the refluxed material to shorten the contact time between the refluxed material and the esophageal mucosa; when the amplitude of esophageal peristalsis is weakened, or disappears, or when pathological peristalsis occurs, the ability of the esophagus to clear the refluxed material through When the amplitude of esophageal peristalsis decreases, or disappears, or when pathological peristalsis occurs, the ability of the esophagus to remove the material through peristalsis decreases, and at the same time, the residence time of the refluxed harmful substances in the esophagus is prolonged, increasing the damage to the mucosa.
The barrier function of esophageal mucosa is damaged by the mucus layer, intracellular buffer, cell metabolism and blood supply. Certain substances in the reflux (mainly gastric acid, pepsin, and to a lesser extent, bile salts and pancreatic enzymes from the duodenal reflux into the stomach) impair the barrier function of the esophageal mucosa, weaken the mucosal resistance, and cause inflammation of the esophageal mucosa.
Gastric and duodenal malfunction
①Gastric emptying hypofunction increases gastric contents and pressure, which can induce les opening when the intragastric pressure increases beyond les pressure; the increased gastric capacity in turn leads to gastric dilatation, resulting in shortening of the pancreatic esophageal segment, which reduces the anti-reflux barrier function. ②In duodenal lesions, incomplete closure of the cardia sphincter leads to duodenal gastric reflux.
Symptoms: Vomiting is the main manifestation in newborns and infants. 80% of children have vomiting in the first week after birth, with varying degrees of severity, mostly after eating, sometimes at night or on an empty stomach, with severe ejections; the vomit is stomach contents, sometimes containing a small amount of bile, and also manifests as milk spillage, regurgitation or foam. In older children, regurgitation, acid reflux, belching and other symptoms are common.
Reflux esophagitis
Common symptoms: ① burning sensation: seen in older children with the ability to express themselves, located in the lower sternum, the symptoms can be aggravated by drinking acidic beverages and alleviated by taking antacids; ② pain in the throat: infants and children show difficulty in feeding, irritability and refusal to eat, older children complain of pain in the throat, if complicated by esophageal stricture, severe vomiting and persistent dysphagia; ③ vomiting and blood in the stool: ulceration and erosion can occur in severe cases of esophagitis. The symptoms of vomiting blood or black stool may occur.
The squamous epithelium at the lower end of the esophagus is replaced by a proliferating columnar dermis. The main comorbidities are esophageal ulcers, strictures and adenocarcinoma. The ulcers are often deep and may result in esophagotracheal fistula.
Other systemic symptoms
1.Aspiration syndrome Reflux directly or indirectly triggers respiratory disease, manifested as recurrent respiratory infections slow
Gastroesophageal reflux disease
The disease is manifested as recurrent respiratory infections, refractory asthma, recurrent aspiration pneumonia, apnea and asphyxia in premature infants, sudden infant death syndrome, etc.
Malnutrition is seen in about 80% of children, mainly manifested as weight gain and growth retardation.
3.Other such as: hoarseness, otitis media, sinusitis, recurrent oral ulcers, dental caries, etc.
Some children may have psychiatric and neurological symptoms: ①sandifer syndrome: pathological ger children present a “cock’s head” posture similar to a sloping neck, accompanied by gastroesophageal reflux, pestle and mortar fingers, protein-losing enteropathy and anemia; ②infant crying syndrome: manifested as irritability, night terrors, crying when eating, etc. The syndrome is characterized by irritability, night terrors, and crying during feeding.
Clinical diagnosis
The clinical manifestations of ger are complex and lack specificity, and it is difficult to distinguish physiological ger or pathological ger based on clinical symptoms alone. at present, it is difficult to confirm the diagnosis by any of the auxiliary tests, and comprehensive diagnostic techniques must be used. Any clinical finding of unexplained recurrent vomiting, dysphagia, recurrent chronic respiratory infections, refractory asthma, growth retardation, malnutrition, anemia, recurrent asphyxia, apnea, etc. should be considered as a possibility of ger presence, and the necessary ancillary tests must be selected for different situations to clarify the diagnosis.
This can be aided by the use of gravity to enhance acid clearance during sleep and reduce nocturnal reflux, which can be assisted by the use of products such as mattress genie (mattress mate). Foods such as fat, chocolate, tea and coffee can reduce LES pressure and appropriate control is advisable. Tobacco and alcohol can weaken the acid contouring ability of the esophagus, reduce the LES pressure and weaken the protective function of the esophageal epithelium, so GERD patients should quit smoking and alcohol. Avoiding a full stomach 3h before bedtime can also reduce nocturnal reflux. 25% of patients can improve their symptoms after changing the above habits.
Drug treatment
If the symptoms of reflux cannot be improved by lifestyle changes, systematic medication should be started. The purpose of treatment is to reduce reflux, relieve symptoms, reduce mucosal damage from refluxed material, and enhance the anti-reflux defense function of esophageal mucosa to cure esophagitis, prevent recurrence, and prevent and treat important complications.
(I) H2 receptor blockers
H2 receptor blockers (H2RAS) are the main drugs currently used in clinical treatment of GERD. These drugs compete with histamine for H2 receptors on gastric lining cells and bind to them, inhibit the acid secretion of histamine-stimulated lining cells and reduce gastric acid secretion, thus reducing the damaging effect of reflux concentration on esophageal lining, relieving symptoms and promoting the healing of damaged esophageal lining.
There are four H2 receptor blockers widely used in clinical practice, namely, cimetidine, ranitidine, famotidine and nizatidine. IT-006 is currently under research than the receptor blocker, its and receptor binding force is stronger than ranitidine, famotidine, and the inhibition of acid secretion is also stronger.
(II) Proton pump inhibitors
Hydrogen-potassium triphosphate adenosine phosphatase (ATPase) is distributed in the cell membrane of the tubular pool and secretory tubules of gastric wall cells. This enzyme is the final pathway that mediates gastric acid secretion, pumping extracellular K+ into the cell and pumping H+ out of the cell, which binds with CL_ to form gastric acid. Proton pump inhibitors (PPIs) inhibit the proton pump in the gastric lining cells through a non-competitive irreversible antagonistic effect, producing a stronger and longer-lasting acid-suppressive effect than H2 receptor blockers. Such drugs commonly used in clinical practice are omeprazole, lansoprazole and toltrazole.
(iii) Prokinetic drugs
GERD is a dysmotic disease, there are often abnormal esophageal and gastric motility, H2RAS and PPI treatment is ineffective, prokinetic drugs can be applied. The efficacy of prokinetic drugs in the treatment of GERS is similar to that of H2RAS, but the effect is significantly better than that of acid suppressants for those with symptoms of dysmotility such as abdominal distention and warmth. For example, Metoclopramide, Domperidone, Cisapride, Levosulpiride, Erythromycin, etc.
(iv) Mucosal protective agents
As a topical agent, aluminum thioglycollate can provide a physical barrier against refluxed gastric contents by adhering to the mucosal surface of the esophagus and has a mild buffering effect on gastric acid, but does not affect the secretion of gastric acid or pepsin and has no effect on LES pressure. The control of GERD symptoms and healing of esophagitis with thioglycollate, taken at 1 g per dose, four times daily, is similar to the efficacy of standard doses of H2RAS. However, it has also been suggested that aluminum thioglycollate is ineffective in GERD.
Magnesium aluminum carbonate can bind the refluxed bile acid and reduce its damage to the mucosa, and can act as a physical barrier to adhere to the mucosal surface. Now it has been widely used in clinical practice.
(E) Other drugs
It is believed that TLESR is the main pathophysiological basis of reflux, and many researchers are working to find drugs that can reduce TLESR for the treatment of GERD, among which atropine and morphine were the first drugs to target TLESR. Loxiglumicle reduces TLESR without affecting the relaxation of the LES during swallowing. Moreover, Loxiglumicle accelerates gastric emptying and colonic transit. Clinical studies have found few side effects, but attention needs to be paid to the effect of gallstone due to its slowing of gallbladder emptying. Another class of drugs that can reduce TLESR are N0 synthase inhibitors, such as NG-monomethyl-L-arginine, which not only inhibit TLESR induced by gastric dilatation, but also accelerate the speed and amplitude of esophageal peristalsis. GABAB receptor agonists such as Baclofen significantly reduced the number of reflux episodes from 1.0 h (0.3-2.7) to 0.3/h (0-1.0) and TLESR from 5.7 Therefore, Baclofen is expected to be an effective drug for GERD treatment.
(vi) Combination therapy
Patients with grade 2-3 esophagitis treated with cimetidine 1g/d combined with cisapride 40mg/d for 12 weeks showed better symptom relief and healing than cimetidine alone. Long-term pH monitoring showed that the combination of cisapride and ranitidine was effective in reducing total reflux, upright reflux and postprandial reflux, and in reducing the recurrence of GERD.
Maintenance therapy
Gastroesophageal reflux disease is a chronic and highly recurrent disease that should be treated for a long time. klinkeberg-Knol et al. reported a 47% recurrence rate in 12 months of drug taper after cure with omeprazole 40 mg/d, emphasizing that maintenance therapy is the key to control GERD.
The use of omeprazole 20 mg once daily as a maintenance dose reduced the relapse rate from 54% – 75% to 11% – 23%. In a 26-month follow-up study, recurrence of reflux symptoms was found to be associated with low pressure in the LES, suggesting that long-term use of prokinetic agents and cisapride 20 mg once daily is effective in preventing recurrence. vigeri suggested that omeprazole 20 mg once daily combined with cisapride 10 mg three times daily is the ideal regimen to prevent recurrence.
Treatment of complications
Common complications of GERD include esophageal stricture, esophageal ulcer, esophageal shortening and Barrett’s esophagus. For mild esophageal strictures, they can be improved by dietary restriction and pharmacological (PPI) treatment. Short-term simple strictures can be treated with Teflon dilators (e.g., Hurst-malonney), and curved or angular strictures can be dilated with endoscopically preplaced guide wires or under x-ray surveillance (Savary dilators, etc.). When the esophageal lumen is reconstructed to 13-15 mm, the patient may be free of dysphagia. If the stenosis worsens progressively, dilatation is recommended every 4-6 months, and stenting is possible if necessary. In some patients, surgical anti-reflux surgery may also be indicated.
Barrett’s esophagus is a serious complication of GERD. Because of its potential for malignancy, endoscopic follow-up and biopsy should be performed for early detection of heterogeneous hyperplasia and adenocarcinoma. When patients have low grade heterogeneous hyperplasia, they can be treated with high dose of PPI, followed by endoscopic follow-up and biopsy after 3-6 months to observe the progress of the disease. In case of moderate to severe heterogeneous hyperplasia or nodular hyperplasia, endoscopic laser, electrocoagulation, member ion coagulation or even local esophagectomy is feasible.
Surgical treatment
Belsey, Nissen and Hill fundoplication are the three most widely used anti-reflux procedures in clinical practice. The purpose of the procedure is to create a ventral segment of the esophagus and to create a “living flap” around the lower esophagus with fundic muscles at the gastroesophageal junction to increase LES pressure. For patients with normal esophageal motility, NiSSen fundoplication is often effective; for patients with esophageal motility disorders, surgery is not effective and postoperative dysphagia is likely to occur, so incomplete surgery (i.e., Toupet fundoplication) is not possible or is the only option. Anti-reflux surgery is effective in relieving symptoms and healing esophageal mucosal damage up to 85%. However, long-term follow-up reveals a 10% recurrence rate. A common complication of anti-reflux surgery is dysphagia. Vagotomy has no benefit for GERD.
The advent of laparoscopic anti-reflux surgery has provided clinicians with a new surgical treatment method, and some clinicians have adopted laparoscopic surgery as one of the preferred methods of anti-reflux surgery.