Infection factors
1, H.pylori infection
Hp infection is the main cause of chronic gastritis (80%-95%), is also one of the important reasons for the formation of CAG, after long-term infection (about 5-25 years), some patients can have gastric mucosal atrophy and intestinalization. NH3, thus maintaining a neutral environment around the bacteria and facilitating their colonization of the gastric mucosal surface.
(1) Hp causes cell damage through ammonia production and secretion of substances such as vacuolar toxin A (vacA).
(2) Cytotoxin-associated gene A (cagA) protein can cause strong inflammatory reflection in gastric mucosa.
(3) The cytosolic wall of the bacterium can act as an antigen to induce immune reflection. The long-term presence of these factors leads to chronic inflammation of the gastric mucosa, and the latter can lead to destruction of the intrinsic gastric glands and atrophy.
2.Other infections
Infection of other pathogenic microorganisms in the gastric mucosa is also correlated with the occurrence of CAG. Some studies have reported an increased detection rate of EBV in patients with CAG, and EBv infection may play an important role in the progression of CAG to gastric cancer. In some regions, fungal detection rates are high in the gastric juice of CAG patients.
Immune mechanism
1.Autoimmune
Gastritis gastric body atrophy dominated chronic gastritis occurs on an autoimmune basis, or type A gastritis. Autoantibodies, namely intrinsic factor antibody (IFA) and parietal cell antibody (PCA), are present in the blood of patients. IFA is divided into two types: type I, also known as blocking antibody, prevents vitamin B12 from binding to intrinsic factor, so that vitamin B12 cannot be absorbed; type II, also known as binding antibody, binds to the intrinsic factor vitamin B12 complex, preventing the absorption of vitamin B12 and leading to pernicious anemia. Mural cell antibody (PCA) has a positive rate of 20% to 60% in general atrophic gastritis, which can reduce the total number of mural cells and lead to a decrease or lack of gastric acid secretion.
2. Other immune factors
Nandelli used the gastric mucosa of type B atrophic gastritis to act on various autoimmune antibodies and found gastrin secretory cell antibody (GCA).GCA is related to type B atrophic gastritis. GCA is a specific autoimmune antibody to G-cell plasma, which belongs to the IgG family and has complement binding ability, suggesting that there are some patients with type B whose lesions are related to G-cell autoimmunity. However, only 10% of gastric sinusitis has GCA, so other causative factors need to be studied.
Cellular immunity: such as lymphocyte transformation, macrophage mobile inhibition, various skin tests and tumor cell killing tests confirm the presence of cellular immunity in chronic gastritis. lymphocytes are commonly seen in the gastric epithelium of CAG, and in some cases mitosis or pseudopods of lymphocytes have been observed, leading to the phenomenon of plasma membrane lysis of adjacent wall cells, indicating that the phenomenon of cellular immunity occurs simultaneously with gastric mucosal lesions during the pathogenesis.
3. Duodenal fluid
Reflux of duodenal fluid, bile, pancreatic fluid and intestinal fluid flow back into the stomach in large quantities, weakening the gastric mucosal barrier function, causing the gastric mucosa to be subjected to the action of digestive juices, producing inflammation, erosion, bleeding and atrophy of the mucosal epithelium, and chemogenic changes.
Bile reflux is considered to be one of the causative factors of CAG. Bile reflux can damage the gastric mucosal barrier, and H+ in the gastric lumen is back-diffused into the gastric mucosa through the damaged barrier, stimulating increased secretion of histamine, which acts on vascular H1 receptors and H2 receptors causing vasodilatation, increased permeability, decreased effective blood flow to the gastric mucosa, and weakened mucosal repair; at the same time, histamine can increase gastric acid secretion and aggravate gastric mucosal damage, thus leading to the occurrence of CAG. In addition, reflux can stimulate gastrin release to inhibit the pyloric sphincter, causing bile reflux to form a vicious circle. Some reports show that the proportion of atrophy, intestinal chemosis and heterogeneous hyperplasia of gastric mucosa in patients with bile reflux gastritis is significantly higher than that in the non-bile reflux group, and the difference is significant (P<0.05).
4.Other factors
(1) Age
The incidence of CAG increases with age, and atrophy, entero-atrophy and heterogeneous hyperplasia also increase and worsen with age. This may be due to small arteriosclerosis and degenerative changes in the gastric mucosa in the elderly, resulting in malnutrition of the mucosa, decreased secretion function and reduced barrier function of the gastric mucosa, becoming an important factor in the occurrence of CAG in the elderly.
(2) Nutritional factors
Vitamin deficiency: The high incidence of CAG is above the age of 50, and a large amount of clinical data has clearly suggested vitamin B12 and folic acid deficiency in the elderly population. Long-term Hp infection will inhibit the secretion of vitamin C from the gastric mucosa, which will decrease the scavenging ability of vitamin C for oxygen free radicals and nitrite, thus aggravating the degree of CAG lesions.
Gastric mucosal trophic factor deficiency: such as gastrin, epidermal growth factor, gastrin suppression, etc., or insensitivity of gastric mucosal sensory nerve terminals to these factors can also cause gastric mucosal atrophy. Chronic iron deficiency and ischemia and hypoxia can cause damage to the gastric mucosa. Certain trace elements such as zinc and selenium deficiency can affect oxygen radical scavenging enzyme activity, which may be related to gastric mucosa damage.
(3) Physical and chemical factors
Lifestyle: At present, domestic and foreign scholars generally believe that the occurrence of CAG has a great relationship with lifestyle and dietary habits, long-term repeated consumption of strong stimulating foods such as strong alcohol, strong tea, coffee, kimchi, too hot or too cold diet, too little intake of fruits and vegetables are associated with the occurrence of CAG.
Medications: Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and Protaxon can cause gastric mucosal erosion, and chronic gastritis can remain after the erosion heals. There are some antibiotics that can damage the gastric mucosa, but there is no evidence that long-term use can cause CAG.
Metal exposure and radiation: Heavy metals such as mercury, copper and zinc have a damaging effect on the gastric mucosa, such as lead workforce gastric mucosa biopsy found an increased incidence of CAG, Palmer called excretory gastritis. Radiation therapy for ulcer disease or other tumors can cause damage or even atrophy of the gastric mucosa.
(4) Genetic
According to Varis survey, the incidence of CAG is significantly higher among the first generation relatives of CAG patients, and the hereditary predisposition to pernicious anemia is also obvious, 20 times larger compared to the control group, and the human hereditary predisposition to susceptibility is an important physical condition for the development of this part of CAG.