Duodenogastric reflux and bile reflux gastritis

　　First, etiology

　　There are also the following factors in the pathogenicity of duodenal reflux fluid:

　　1. Bile has a greater damaging effect on gastric mucosa in an acidic medium, especially under ischemic conditions.

　　2. Bile, pancreatic juice, and duodenal fluid containing hemolytic lecithin have the greatest destructive effect on gastric mucosa.

　　3. In patients with gastric ulcer, those with a higher concentration of bile in the stomach, the growth of Gram-negative aerobic bacteria in gastrointestinal aspirate increases.

　　4. In patients with clinical symptoms, the concentration of deoxycholic acid in gastric juice increases.

　　5. Delayed gastric emptying prolongs the contact time between bile and gastric mucosa.

　　Second, pathogenesis

　　1. The pathogenesis of GR:Gastric motility physiological research proves that the pylorus is mostly in an open state, and a small amount of duodenal reflux into the stomach is not enough to cause symptoms or damage the gastric mucosa, which is called physiological DGR. The occurrence of large amounts of DGR is often common in the following situations:

　　(1) DGR after gastric surgery: The incidence of postoperative gastric DGR is 5% to 60%. Postoperative gastric DGR is caused by the damage to the normal anatomical structure and physiological function of the pylorus, resulting in the loss of the pyloric anti-DGR barrier function, leading to the reflux of excessive bile-containing alkaline intestinal fluid into the stomach, and causing residual gastritis and bile vomiting. Griffiths reported 71 cases of postoperative stomach, with 41.9% showing bile reflux and 61.5% having diffuse gastritis. Bile reflux from the duodenum or small intestine to the stomach after gastric surgery, since part of the surgery is a gastrojejunostomy, it should be accurately called jejunoenteric reflux. The severity of jejunoenteric reflux is obviously related to the surgical method, and is arranged in order of severity as follows:

　　①Pyloric shaping surgery.

　　② Vagotomy combined with pyloroplasty.

　　③ Gastrojejunal anastomosis.

　　④ BillrothⅠ type gastric resection.

　　⑤ BillrothⅡ type gastric resection.

　　(2) Primary pyloric dysfunction: Modern research on gastrointestinal motility function proves that some pathological DGR is not due to post-gastric surgery, but originates from the defect of the pylorus itself, such as pyloric sphincter dysfunction, such as prolonged pyloric opening time, dysfunction of the pyloric hypertension zone, and other factors lead to a large amount of duodenal contents refluxing into the stomach.

　　In 1973, Fisher measured the pressure of the pyloric hypertension zone using the perfusion method as (5.3±0.5) mmHg. Zhang Jinkun and Luo Jinyan in China have also confirmed the existence of the pyloric hypertension zone using the intracavitary metallic sensor method. People believe that the gastric duodenal barrier pressure (GDBP = pyloric pressure - duodenal pressure) has an anti-reflux effect. When GDBP decreases, it causes DGR to occur. Chinese reports show that the gastric duodenal barrier pressure of DGR patients is lower than that of the normal control group.

　　Animal experiments have observed that during the migrating motor complex Ⅱ phase of digestion, due to atypical segmental contractions accompanied by DGR.

　　① During the MMCⅡ phase, bile and pancreatic secretions accumulate in the duodenum.

　　② Due to the small rule movement and pressure changes in the MMCⅡ phase, a certain pressure gradient is produced, which increases the intraduodenal pressure and causes gastroenteric reflux.

　　(3) Delayed gastric emptying: Whether idiopathic or secondary delayed gastric emptying (such as idiopathic gastroparesis, diabetic gastroparesis), due to the dysfunction of gastric peristalsis and pylorus, it leads to a decrease in GDBP and a large amount of duodenal reflux. Once DGR occurs, it can further slow down gastric emptying, so some people believe that delayed gastric emptying and DGR can be mutually causal (delayed gastric emptying

　　DGR).

　　(4) Liver and biliary diseases: Patients with liver cirrhosis and portal hypertension have a high incidence of DGR. The mechanism is believed to be due to circulatory disorders caused by portal hypertension, coupled with secondary hypergastrinemia, which inhibits the regulation of cholecystokinin and secretin on the pyloric sphincter and Oddi's sphincter, causing a decrease in the tone of the latter two, and the reflux of bile and pancreatic juice into the stomach.

　　Many biliary tract diseases (such as cholecystitis, gallstones, and post-cholecystectomy) are accompanied by obvious DGR phenomena. Due to biliary tract diseases, the function of gallbladder reserve and bile concentration is reduced and disappeared, causing bile to flow continuously from the bile duct into the duodenum and reflux into the stomach through the pylorus.

　　Autonomic nervous dysfunction, excessive smoking, drinking, emotional fluctuations, changes in lifestyle, and other conditions can cause紊乱 in the secretion of gastrointestinal hormones, and lead to retrograde peristalsis of the antrum and duodenum and a decrease in the tone of the pylorus, resulting in an imbalance in the motor function of the stomach and duodenum, providing the necessary pressure gradient for the reflux of material through the pylorus, and promoting the occurrence of DGR.

　　Pathogenesis of bile reflux gastritis (BRG)

　　Gastric surgery, such as subtotal gastrectomy, usually leads to residual gastritis or bile reflux gastritis (BRG) due to bile reflux in a few months or years later, and symptoms such as upper abdominal pain or vomiting bile may occur.

　　A large number of animal experiments and clinical observations have proven that the reflux of bile and duodenal contents into the stomach can cause gastritis, and it has been found that the extent and severity of gastritis are linearly related to the degree of bile reflux and are related to the reflux components. Bile acids and lysophosphatidylcholine are the main components that damage the gastric mucosa. Bile salts can dissolve phospholipids and cholesterol from the gastric mucosa and interfere with the energy metabolism of gastric mucosal epithelial cells, causing lysosomes to rupture, and at the same time, they have a clearing effect on the mucus on the surface of the gastric mucosa, damaging the gastric mucosal barrier, increasing the reverse diffusion of H, and thus causing mast cells to release histamine, leading to the occurrence of gastritis. A large number of DGR not only directly damage the gastric mucosa to cause gastritis but are also related to the occurrence of gastric ulcers. Rhodes J et al. (1972) found that the DGR in patients with gastric ulcers was higher than that in normal people, and the mechanism may be through the excessive damage of the gastric mucosa by cytotoxic bile salts and trypsin, followed by proliferative changes, intestinal metaplasia, and the formation of ulcers. In addition, DGR can reflux into the esophagus simultaneously, playing an important role in the pathogenesis of reflux esophagitis and Barrett's esophagus, known as duodenogastric esophageal reflux (DGER). Some studies have reported that DGR is also related to the occurrence of esophageal cancer and residual gastric cancer.

　　Patients often have symptoms such as anemia, weight loss, chronic diarrhea, insomnia with frequent dreams, palpitations, and other neurotic symptoms.

　　1. Anemia:A condition in which the red blood cell count, hemoglobin content, and hematocrit in a certain volume of circulating blood are all below the normal standard is called anemia. Among them, hemoglobin is the most important. Adult males with hemoglobin below 120g/L (12.0g/dl) and adult females with hemoglobin below 110g/L (11.0/dl) are generally considered to have anemia.

　　2. Diarrhea:It is a common symptom, referring to a significant increase in defecation frequency compared to the usual habits, thin stools, increased water content, daily defecation volume exceeding 200g, or containing undigested food or pus and mucus. Diarrhea is often accompanied by symptoms such as urgent defecation, anal discomfort, and incontinence. Diarrhea is classified into acute and chronic types.

　　3. Palpitations:It is commonly referred to as palpitations, which is an uncomfortable feeling of heart palpitations. Palpitations can be caused by changes in the frequency, rhythm, or contraction strength of heart activity, or they can occur even when the heart activity is completely normal, the latter being due to people's particular sensitivity to their own heart activity.

　　Patients often complain of persistent pain in the upper and middle abdomen, which worsens after meals, and antacids are ineffective, even exacerbating the symptoms. Some patients may present with pain behind the sternum, a feeling of indigestion, and often vomit 'bitter water' or bile in the evening or early morning on an empty stomach, sometimes mixed with food. The vomiting does not alleviate the symptoms. Patients often have anemia, weight loss, chronic diarrhea, insomnia with frequent dreams, palpitations, and other neurotic symptoms, and the physical signs are often表现为上腹压痛苦.

　　1. If DGR and BRG are caused by post-gastric surgery, the choice of surgical method is very important.

　　2. If DGR is caused by autonomic nerve dysfunction, excessive smoking, drinking, and changes in life routine leading to disorder of gastrointestinal hormone secretion, it is very important to strengthen physical exercise and change lifestyles.

　　3. Specific dietary recommendations should be consulted with a doctor based on symptoms, ensuring a reasonable diet and a comprehensive and balanced nutrition.

　　4. Eat more vegetables and fruits, and keep the diet light. Abstain from smoking and drinking, and avoid spicy and irritating foods.

　　First, laboratory examination:

　　Many techniques are used to detect and evaluate DGR, and efforts are made to distinguish physiological DGR from pathological DGR. In recent years, with the continuous progress and development of biomedical engineering technology, clinical evaluation of DGR has become more objective.

　　1. Monitoring of gastric pH value:Continuous monitoring of 24h gastric pH value can be an effective method for detecting DGR. The experiment is conducted under approximate physiological conditions and can obtain all the data of daytime (including meals, postprandial), and 24-hour standing and lying posture at night. Normally, the gastric pH value of fasting individuals is rarely greater than 2, and the pH value increases after eating and postprandial, which can rise to above 4.0 during meals, and about 30-40 minutes to return to baseline. Short-term pH value increases can be seen in the latter half of the night or in the early morning, with pH values rising from baseline to 4-6. Some people call this phenomenon pH reversal or alkalization of gastric juice, which may be related to duodenogastric reflux. Some believe it is related to weakened vagal nerve activity or low acid secretion function. A research report by Gong Jun from China shows that the fasting gastric juice pH of healthy individuals is about 2.0, with three pH value rises related to diet during the day, and spontaneous pH value rises between 0:40 and 4:33 in the early morning may be related to duodenogastric reflux. Studies have shown that normal individuals also have DGR, but the duration is short, about 1 hour, and the occurrence frequency is low, with significantly more time above 4.

　　2. Determination of Na in gastric juice:The concentration of Na in duodenal juice is relatively high, and it remains stable at about 146 mmol/L, which is more stable than the concentration of bile in intestinal juice (bile is intermittent in entering the intestines), and the Na that refluxes back into the stomach is not destroyed or inactivated by gastric acid, and it also has the advantage of easy detection, making it a diagnostic indicator for DGR. Some studies have shown that simultaneous monitoring of gastric pH value and timed determination of Na and bile acid content in gastric juice can reveal a good linear relationship among the three. The detection of Na concentration is a simple and feasible method to judge DGR. Our hospital has measured the Na concentration in fasting gastric juice of DGR (+) gastritis group (28 cases) and DGR (-) gastritis group (24 cases), with the DGR (+) group being (62.87±8.31) mmol/L and the DGR (-) group being (32.18±4.67) mmol/L. The difference in Na content between the two groups is significant (P

　　3. Determination of fasting gastric juice bilirubic acid:Bilirubic acid is commonly found in the stomach of patients with DGR and is not destroyed by gastric acid, which can serve as a 'marker' for duodenal fluid. Determining its concentration in gastric juice is of great significance for understanding the degree of reflux. However, the stimulation during the intubation process is prone to cause artificial reflux. Even if fasting gastric juice is collected, the content of bilirubic acid will be affected, and false-positive results may occur. On the other hand, the presence of bile in duodenal fluid depends on the emptying of the gallbladder. If bile is not excreted into the duodenum, false-negative results may occur. The application of 99mTc-EHIDA scanning shows that the average interval time for gallbladder contraction is 70 minutes, therefore, continuously collecting gastric juice and determining its bilirubic acid content can improve the positive rate of DGR diagnosis. Some authors have adopted continuous aspiration of gastric juice for 90 minutes, with a standard for diagnosing DGR as a total bile acid content ≥100μmol/h or a bilirubic acid concentration ≥1000μmol/L. Compared with radionuclide, the former has an accuracy rate of 80%, and the latter has an accuracy rate of 70%.

　　4. Microbilirubin Determination:The main components of the 24h bile reflux monitoring instrument DGR are alkaline intestinal fluid, bile, and pancreatic enzymes, etc. The presence of bilirubin is used to assess whether DGR occurs, physiological versus pathological, and the recent application of optical fiber sensing technology designed by Bilitec (2000) has been introduced. The characteristic absorption spectral peak of bilirubin is at 450nm. With this technology, not only can DGR be qualitatively determined, but also the amount of bile reflux can be quantitatively assessed. Through the analysis of multiple parameters, it is of great significance in evaluating bile reflux, and it can also monitor the situation of gastroesophageal bile reflux, commonly used in Barrett's esophagus, esophagitis due to ineffective acid reflux medication, and the evaluation of residual gastritis after gastric resection, etc. The examination requires fasting for more than 6 hours, inserting a tube through the nose, placing the sensor 5cm below the lower esophageal sphincter, consuming a standard meal (restricted to alcohol, beverages, and acidic foods as well as dyes, etc.), fixing the catheter, and wearing a portable recorder for 24-hour portable monitoring. The results are processed and analyzed by microcomputer software, including the total number of bile refluxes in 24 hours, the number of refluxes exceeding 5 minutes, the longest reflux time, and the percentage of total reflux time. This technology detects bile reflux, and therefore, it is affected by the MMC phase, and it is not applicable in certain liver diseases such as congenital bilirubinemia (Gilbert's disease and Dubin-Johnson syndrome). Additionally, in an acidic environment, due to the conversion of bilirubin into dimers, the peak of light absorption changes from 453nm to 400nm, and the detection value will decrease.

　　Second, imaging examination

　　1. Gastroscopy and histological examination:Gastroscopy can directly observe bile reflux, the gastric mucosa is stained yellow, and it is visible that the gastric mucosa is congested and edematous,呈颗粒状, and the vascular changes are more obvious. The tissue is fragile or ulcerated, with necrosis and hemorrhagic foci. Histological examination: in addition to the obvious infiltration of inflammatory cells, small areas of erosion, necrosis, metaplasia, atypical hyperplasia, and other changes can also be seen. Endoscopy can understand the degree of reflux and the severity of gastritis, but endoscopy cannot be quantified, and the endoscopy itself can cause reflux, so there is a high rate of false positives.

　　2. Radiological examination:Early diagnosis of DGR was done by catheterization, inserting a catheter into the duodenum, injecting barium sulfate solution, and observing the reflux of barium into the stomach under X-ray fluoroscopy. Due to the discomfort caused by catheterization and the impact on the physiological function of the pylorus, and the subjective coloration in judgment, the false positive rate is relatively high, and this method is basically abandoned now.

　　3. Gastrointestinal pressure measurement:The pressure in the antrum, pylorus, and duodenal ampulla is measured using a pressure sensor or perfusion catheter. Most DGR patients have a decrease in antrum and pylorus pressure, and an increase in duodenal ampulla pressure.

　　4. Gastrointestinal alkali perfusion irritation test:When upper abdominal pain occurs after the stomach is infused with an alkaline solution (0.1NNaOH 20ml/time), and whether accompanied by nausea or not, it is listed as infusion positive. This test is sensitive, simple, and specific.

　　5. Nuclide examination:Using a radioactive nuclide scintigraphy that excretes through the liver via bile, reflux can be determined non-invasively, without mechanical stimulation and under approximate physiological conditions, which can accurately determine the presence and amount of reflux. Currently, scholars outside of China generally believe that the 99mTcEHIDA radioactive nuclide scanning technology is the 'gold standard' for DGR quantification, superior to gastroscopy and fasting bile acid determination. This method has a high sensitivity, and it is positive when the ratio of radioactive activity in the stomach to the total injected amount is greater than 1%. It also has good reproducibility (75%), and has become a very valuable research tool and clinical diagnostic method.

　　But the radioactive nuclide examination also has certain defects, as the anatomical position of the stomach is difficult to accurately locate, which reduces the accuracy of this technology and affects the quantitative results of DGR. The radioactive nuclide concentration area of the stomach is often difficult to represent the true contour of the stomach, especially the antrum is even more difficult to depict. The coverage of the liver, duodenum-intestinal loop will also affect its accuracy. Although the range can be limited, the activity of these areas is often not constant. The difficulty in determining the radioactive nuclide concentration area increases with the patient's body movement when lying or standing. All these factors can cause diagnostic bias.

　　6. Ultrasound examination King:PM et al. (1984) first used real-time ultrasound to detect DGR, followed by HauskenT et al. (1991) using color Doppler ultrasound technology to observe the flow and reflux of gastric contents, which represents a leap in the technology of DGR assessment, being non-invasive, with good repeatability, and can quantify DGR. The specific steps are as follows: fasting for one night, taking a sitting position, consuming a liquid test meal (400ml of broth or milk) within 2 minutes, placing the probe at the level of the pylorus, observing the antrum, pylorus, and proximal duodenum, and judging whether there is reflux according to the color signals (the liquid flowing towards the distal end is blue, and reflux is red). The severity of DGR can be assessed according to its frequency and intensity. The drawback of this technology is that it can only be used to measure DGR with a liquid test meal, and at the same time, due to factors such as intestinal bloating or thick abdominal wall fat layer, it often brings some technical difficulties.

　　In recent years, people have begun to pay attention to the application of gastric mucosal protective agents against the damage of bile reflux to gastric mucosa, such as:

　　1. Prostaglandin E:It has a protective effect on gastric mucosal cells, can stimulate the secretion of mucus and HCO3-, dilate blood vessels, promote blood circulation in the mucosa, inhibit the secretion of gastric acid and pepsin, and increase exogenous PGE1.

　　2. Tiprenone:It is a terpenoid substance that can promote the biosynthesis of glycolipid intermediates in the microsomes of the gastric mucosa, thereby accelerating the synthesis of the main mucosal repair factor in the gastric mucosa and gastric mucus layer, which is high molecular weight glycoprotein, and increase the concentration of phospholipids in the mucus, thereby improving the defensive function of the mucosa.

　　3. Hexagonal montmorillonite (Simida):Primarily to strengthen the protective function of the gastric mucosal barrier, fix and eliminate the effects of viruses and bacteria, adsorb gases in the digestive tract, and resist the invasion of various attacking factors. Prokinetic drugs: drugs such as metoclopramide (Ganfuxing), domperidone (Mandiling), cimetidine tablets, mosapride, and Six Flavor Anxiao San can enhance the contraction of the corpus and antrum of the stomach, increase the tension of the stomach, improve the coordination between the antrum and duodenum, accelerate gastric emptying, prevent and treat bile reflux, and regulate and restore gastrointestinal motility.

　　4. Prokinetic drugs:Drugs such as metoclopramide (Ganfuxing), domperidone (Mandiling), cimetidine tablets, mosapride, and Six Flavor Anxiao San can enhance the contraction of the corpus and antrum of the stomach, increase the tension of the stomach, improve the coordination between the antrum and duodenum, accelerate gastric emptying, prevent and treat bile reflux, and regulate and restore gastrointestinal motility.

　　I. Treatment

　　1. Internal medicine treatment

　　(1) General treatment: Bed rest, light diet, small and frequent meals, quit smoking and alcohol.

　　(2) Medication: Use drugs that can inhibit or reduce reflux and protect the gastric mucosa. The following drugs can be selected.

　　① Colestipol (Cholestyramine) is an anion exchange resin with affinity for bile acids. After taking it, it can bind with bile acids to reduce the concentration of soluble bile acids, prevent the occurrence of gastritis, and requires supplementation of fat-soluble vitamins if the medication duration exceeds 3 months.

　　② Domperidone is a dopamine receptor antagonist for the stomach, which strengthens gastrointestinal motility, promotes gastric emptying, and reduces the contact time of bile salts and mucosa.

　　③ The new generation of gastrointestinal promotors cisapride (Pride) is a 5-HT4 receptor agonist. By exciting cholinergic receptors, it increases the release of acetylcholine in the myenteric plexus, coordinates the movement of the gastric antrum, pylorus, and duodenum to increase gastric emptying, and has a good therapeutic effect on controlling the occurrence of DGR.

　　④ Since bile acid needs to be mediated by H2 to cause damage to the gastric mucosa, anti-secretory drugs have a certain protective effect on the gastric mucosa.

　　⑤ Ursodeoxycholic acid (UDCA) can inhibit the synthesis of bile acid, and after taking it, a large amount of ursodeoxycholic acid is excreted in bile, which reduces the concentration of deoxycholic acid and lithocholic acid relatively, so it has a good therapeutic effect.

　　⑥ Aluminum hydroxide magnesium (Gastadex, Talcid) is a layered lattice structure, which can quickly neutralize stomach acid, reversibly inactivate pepsin, continuously prevent bile acid and hemolytic lecithin from damaging the gastric mucosa, enhance the protective factor of the gastric mucosa, and achieve an overall effective rate of up to 90% in the treatment of bile reflux gastritis. In addition, double octahedral montmorillonite (Simeticon), compound glutamine (Mizulin-S), compound trisilicate magnesium (Gawei Ping), sodium glycyrrhizinate (Shengweikang), and branched-chain starch can also be selected.

　　(3) Parenteral Nutrition Therapy: Keeps the gastrointestinal tract in a resting state, reduces the occurrence of bile reflux, and supplements necessary calories and electrolytes.

　　2. Surgical Treatment:Some patients, especially those with severe conditions, have little or no effect from medication, and often require surgical treatment. There are several surgical methods, but the Roux-en-Y operation is the most effective.

　　II. Prognosis

　　Most patients recover well after internal medicine treatment. Some patients, especially those with severe conditions, have little or no effect from medication, and often require surgical treatment.