Chronic gastritis

Chronic gastritis is a group of chronic diseases that are morphologically characterized by inflammatory and dystrophic processes, impaired physiological regeneration and, as a result, atrophy of the glandular epithelium (with a progressive course), intestinal metaplasia, and disorders of the secretory, motor and endocrine functions of the stomach.

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Epidemiology

The disease is widespread, occurring in more than half of the adult population, but only 10-15% of people with chronic gastritis consult a doctor. Chronic gastritis accounts for 85% of all stomach diseases.

The prevalence of chronic gastritis is estimated at approximately 50-80% of the entire adult population; with age, the incidence of chronic gastritis increases. The vast majority of cases of chronic gastritis (85-90%) are associated with Helicobacter pylori infection, the etiologic role of which has been proven.

Chronic autoimmune gastritis, characterized by the formation of antibodies to parietal cells and Castle's intrinsic factor, is observed 3 times more often in women. Such patients have a significantly increased risk of pernicious anemia.

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Causes chronic gastritis

Helicobacter pylori infection is the most common cause of chronic gastritis. According to research, Helicobacter pylori is the cause of gastritis in 95% of cases.

In 1983, B. Marshall and D. Warren isolated a microorganism called Helicobacter pylori from a biopsy of the gastric mucosa of a patient with antral gastritis. Helicobacter pylori are microaerophilic, non-negative bacteria with a curved S-shaped or slightly spiral shape. The thickness of the bacteria is 0.5-1.0 μm, the length is 2.5-3.5 μm. The bacterial cell is covered with a smooth membrane, one of the poles has from 2 to 6 monomeric flagella. Currently, 9 species of Helicobacter are known. It has been established that Helicobacter produces a number of enzymes: urease, alkaline phosphatase, glucosphosphatase, protease, mucinase, phospholipase, superoxide dismutase, as well as hemolysin, vacuolating cytotoxin, protein that inhibits hydrochloric acid secretion, and adhesin proteins.

Due to their structure and production of the above-mentioned substances, Helicobacter pylori are able to overcome protective barriers in the stomach cavity, attach to the cells of the gastric epithelium, colonize the gastric mucosa, damage it and cause the development of chronic gastritis.

The natural habitat for Helicobacter is the mucus of the stomach, in addition, they are often found deep in the gastric pits, concentrating in the intercellular connections. Helicobacter also adheres to the cells of the gastric mucosa.

Thanks to the flagella, the bacteria move in a corkscrew-like motion and come into contact with the gastric epithelium.

The most favorable conditions for the existence of Helicobacter are a temperature of 37-42°C and a pH of the gastric contents of 4-6, but bacteria can also survive in an environment with a pH of 2.

Two circumstances contribute to a decrease in Helicobacter colonization: widespread atrophy of the gastric glands with intestinal-type metaplasia of the gastric epithelium and hypochlorhydria.

Currently, the role of Helicobacter in the development of chronic gastritis is considered proven, chronic gastritis caused by Helicobacter is called Helicobacter or associated with Helicobacter infection. It accounts for about 80% of all types of chronic gastritis.

According to scientific research, H. pylori causes antral gastritis in 95% of cases and pangastritis in 56%.

An almost 100% relationship has been established between Helicobacter infection, chronic gastritis and peptic ulcers.

Helicobacter infection is very widespread among the population. It is more often detected in the older age group, and at the age of 60, more than half of the population of developed countries can be infected. In developing countries, the infection is spread to a much greater extent, and the age at which infection begins is much younger.

According to the discoverer of Helicobacter pylori, Marshall (1994), in developed countries H. pylori is found in 20% of people over 40 years of age and in 50% of people over 60 years of age.

It has now been established that the source of infection is a person - a patient or a carrier of bacteria (Mitchell, 1989). Helicobacter can be found in saliva, feces, and dental plaque. Helicobacter infection is transmitted orally and feco-orally. Oral-oral infection is also possible during gastric probing and fibrogastroscopy if imperfect disinfection methods are used during sterilization of endoscopes and probes. Under unfavorable conditions, Helicobacter acquires a coccoid form, is dormant, and loses the ability to reproduce as a result of decreased enzyme activity. However, when Helicobacter enters favorable conditions, they become active again.

Chronic Helicobacter gastritis is initially localized in the antral region, then as the disease progresses, the body of the stomach or the entire stomach (pangastritis) is involved in the pathological process.

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Autoimmune factor

In approximately 15-18% of cases, chronic gastritis is caused by the development of autoimmune processes - the formation of autoantibodies to the parietal (lining) cells of the gastric mucosa, which produce hydrochloric acid and Castle's intrinsic factor gastromucoprotein.

Autoimmune gastritis is localized in the fundus of the stomach and its body; parietal cells are concentrated in these areas.

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Duodenogastric reflux

A common cause of chronic gastritis is duodenogastric reflux. It is caused by insufficiency of the pyloric closure function, chronic duodenostasis and associated hypertensia in the duodenum.

With duodenogastric reflux, duodenal and pancreatic juice mixed with bile is thrown into the stomach, which leads to the destruction of the mucous barrier (primarily in the antral part of the stomach) and the formation of reflux gastritis. Often, such gastritis develops as a result of gastric resection and reconstructive surgeries on the stomach.

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Treatment with gastrotropic drugs

In some cases, chronic gastritis develops against the background of treatment (especially with long-term oral administration) with drugs that have a damaging effect on the gastric mucosa and destroy the protective mucous barrier. These drugs include salicylates (primarily acetylsalicylic acid); NSAIDs (indomethacin, butadiene, etc.); potassium chloride; reserpine and drugs containing it; anti-tuberculosis drugs, etc.

Food allergy

Food allergy is often associated with gastrointestinal pathology, in particular with chronic gastritis. Patients with food allergies often have inflammatory changes in the gastric mucosa, an increase in the number of plasma cells synthesizing immunoglobulins E, G, M. Eosinophilic infiltration and mast cells are found in biopsies of the gastric mucosa.

Chronic gastritis can develop with food allergies to dairy products, fish, eggs, chocolate, etc. The role of food allergies in the development of chronic gastritis is proven by the disappearance of the clinical and histological picture of the disease against the background of the elimination of the allergen product.

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Alimentary factor

In recent years, after the leading role of Helicobacter pylori in the development of chronic gastritis was established, the alimentary factor is not given such significant importance as before. However, clinical observations indicate that the following factors may have a certain significance in the development of chronic gastritis:

• disturbance of the eating rhythm (irregular, hasty eating with insufficient chewing of food);
• consumption of poor quality food;
• abuse of very spicy food (pepper, mustard, vinegar, adjika, etc.), especially by people for whom such a diet is not habitual. It has been established that extractive substances significantly increase the production of gastric juice and hydrochloric acid, and with prolonged, many-year use, they deplete the functional capabilities of the gastric glands. Marinades, smoked foods, heavily fried dishes, when consumed frequently, can cause chronic gastritis. Experiments on dogs showed that systematic feeding them red ground pepper initially caused gastritis with increased, and then decreased gastric secretion;
• Abuse of very hot or very cold food also contributes to the development of chronic gastritis.

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Alcohol abuse

Alcohol, when consumed frequently and for a long time, causes the development of superficial gastritis at first, and later - atrophic gastritis. The likelihood of developing chronic gastritis is especially high when consuming strong drinks and alcohol substitutes.

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Smoking

Long-term smoking over many years contributes to the development of chronic gastritis (the so-called smoker's gastritis). Nicotine and other components of tobacco smoke disrupt the regeneration of the gastric epithelium, initially increase and then decrease the secretory function of the stomach, and damage the protective mucous barrier.

The impact of occupational hazards

Industrial factors can cause the development of occupational toxic gastritis. This can occur when harmful components contained in the air are swallowed: coal, metal, cotton and other types of dust, acid vapors, alkalis and other toxic and irritating substances for the gastric mucosa.

Impact of endogenous factors

Endogenous factors that cause chronic gastritis include:

• chronic infections (oral cavity, nasopharynx, non-specific inflammatory diseases of the respiratory system, tuberculosis, etc.);
• endocrine system diseases;
• metabolic disorders (obesity, gout);
• iron deficiency in the body;
• diseases leading to tissue hypoxia (pulmonary and cardiac failure of various origins);
• autointoxication in chronic renal failure (release of toxic products of nitrogen metabolism by the gastric mucosa).

Among endogenous factors, chronic inflammatory diseases of the abdominal organs are of the greatest importance due to their significant prevalence (chronic cholecystitis, pancreatitis, hepatitis, enteritis, colitis). These diseases are accompanied by neuroreflex disorders of the motor-evacuation function of the stomach, reflux of the contents of the duodenum with bile acids and pancreatic enzymes that damage the gastric mucosa; reflex disorders of blood circulation in the gastric mucosa; direct transition of the inflammatory process to the stomach; intoxication and allergic effects on the gastric mucosa.

Endocrine diseases are also a current cause of chronic gastritis.

In chronic adrenal insufficiency, gastric secretion decreases and gastric mucosa atrophy is observed; in diffuse toxic goiter, gastric secretion initially increases, and then chronic gastritis with decreased secretory function develops; diabetes mellitus is often accompanied by gastric mucosa atrophy; in hypothyroidism, chronic gastritis with decreased secretory function develops; in Itsenko-Cushing's disease and hyperparathyroidism - with increased secretory function.

Probably, with endocrine diseases, pronounced dystrophic changes in the mucous membrane, disturbances of its secretory function, and later inflammation develop.

Among all the above-mentioned causes of chronic gastritis, the most significant and reliable are Helicobacter infection and autoimmune factors; accordingly, Helicobacter and autoimmune gastritis are distinguished.

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Pathogenesis

Pathogenesis of Helicobacter gastritis

Helicobacter pylori enter the lumen of the stomach with contaminated food, with swallowed saliva, or from the surface of an insufficiently disinfected gastroscope or gastric tube.

Urea is present in the stomach, it penetrates from the bloodstream by sweating through the capillary wall. Under the influence of the enzyme urease, Helicobacter pylori forms ammonia from urea. Ammonia neutralizes the hydrochloric acid of the gastric juice and creates a local alkaline environment around Helicobacter pylori, which is very favorable for its existence.

In addition, under the influence of the mucinase enzyme secreted by Helicobacter, the protein mucin contained in the gastric mucus is destroyed. As a result, a zone of local reduction in the viscosity of the gastric mucus is formed around the Helicobacter.

Due to the ammonia environment and the local zone of mucus with reduced viscosity, as well as the spiral shape and high mobility, Helicobacter from the lumen of the stomach easily penetrate the protective mucus layer and adhere to the integumentary-pit epithelium of the antral part of the stomach. Some Helicobacter penetrates the lamina propria through the interepithelial spaces.

Next, Helicobacter pylori pass through the protective mucus layer and reach the mucous membrane lined with mucus-producing epithelial cells, as well as endocrine cells that produce gastrin and somatostatin.

Only on the surface of mucus-forming cells of the columnar epithelium are there receptors for Helicobacter adhesins.

There are 5 classes of Helicobacter adhesins (Logan, 1996):

• Class 1 - Fimbrial hemagglutinin; Hemagglutinin specific for sialic acid (20 kDa);
• Class 2 - Non-fimbrial hemagglutinins: sialic acid-specific (60 kDa), unidentified surface hemagglutinins;
• Class 3 - Lipid-binding gangliotetraosylceramides;
• Class 4 - Sulfamucin binders (sulfatide, heparan sulfate);
• Class 5 - Adhesins interacting with antigens of erythrocytes of blood group O(I) (Lewis).

Helicobacter adhesins bind to receptors of the gastric epithelium. This connection itself and the location of Helicobacter on the surface of the gastric mucosa have a damaging effect on epithelial cells, dystrophic changes occur in them, and their functional activity decreases. Helicobacter multiplies intensively, completely populates (colonizes) the mucous membrane of the antral part of the stomach and causes its inflammation and damage due to the following main mechanisms:

• Helicobacteria secrete enzymes phospholipase, protease, and mucinase, which destroy the protective mucous barrier of the stomach;
• Helicobacteria, with the help of the enzyme urease, break down urea into ammonia and CO2, which leads to a sharp alkalization of the membranes of the cells of the gastric epithelium, which disrupts the homeostasis of the cells, causes their dystrophy and death and facilitates the penetration of Helicobacter into the mucous membrane;
• ammonia formed under the influence of Helicobacter pylori has a dual effect on the endocrine cells of the gastric mucosa: gastrin secretion is enhanced and somatostatin is suppressed, which leads to increased secretion of hydrochloric acid and, naturally, to increased acidity of gastric juice. The latter circumstance should be considered an aggressive factor in the initial stage of Helicobacter pylori infection;
• Helicobacter induces the production and release of inflammatory mediators. Macrophages and leukocytes are the first to react to Helicobacter penetration into the gastric mucosa. These cells rush into the gastric mucosa and phagocytize Helicobacter and, consequently, their antigens. Then T-helper lymphocytes are activated (under the influence of interleukin-1 secreted by macrophages), which ensure the blast transformation of B-lymphocytes into plasma cells. The latter produce antibodies to Helicobacter. Macchia et al. (1997) found that Helicobacter produces heat shock proteins, which initiate antibody formation. During the process of phagocytosis of Helicobacter and the formation of antibodies to them, various cytokines are released that participate in the development of the inflammatory process in the gastric mucosa. The resulting antibodies to Helicobacter enter not only the blood, but also the submucosal layer of the stomach, where they bind to Helicobacter and neutralize their toxins and contribute to their death. In the gastric mucosa, the production of predominantly IgA antibodies is increased, which have the ability to prevent the adhesion of Helicobacter by blocking the receptors with which they are fixed to epithelial cells. Thus, it is IgA antibodies that play a protective role in Helicobacter infection. However, in chronic Helicobacter gastritis, the protective function of anti-Helicobacter antibodies of the IgA class is clearly insufficient. Along with IgA, IgG and IgM antibodies are formed, which activate complement and initiate the development of a neutrophilic reaction;
• in response to the interaction of Helicobacter with the gastric epithelium, the latter produces a large amount of interleukin-1 and interleukin-8. This process is stimulated by the endotoxin of Helicobacter. Interleukins-1 and 8 cause neutrophil chemotaxis and stimulate the formation of free radicals by them, causing damage to the gastric epithelium. Cytokines also cause degranulation of mast cells, the release of histamine from them, which sharply increases vascular permeability and promotes the entry of neutrophils, lymphocytes, and macrophages into the site of inflammation;
• Full-fledged S-shaped forms of Helicobacter produce cytotoxins - vacuolating and CaGA toxin ("associated" protein), under the influence of which the gastric mucosa undergoes pronounced structural changes. The degree of damage to the gastric mucosa can be quite significant - up to the formation of erosion or even ulcers. This is facilitated by the stimulation of the vacuolating toxin and CaGA toxin of the production of interleukin-8 - an intense mediator of inflammatory reactions. There are no Helicobacter in the ulcer itself, since it does not have adhesive and epithelial cells. If Helicobacter does not produce vacuolating cytotoxin, then erosion and ulceration do not occur and the process of damage to the gastric mucosa stops at the stage of chronic gastritis.

Thus, Helicobacter infection has not only a local pathogenic effect on the gastric mucosa (immunoinflammatory process with migration and infiltration of immunocompetent cells into the inflammation site, their activation, synthesis of inflammation mediators and destruction), but also causes a systemic specific humoral and cellular immune response with the development of antibody-dependent and cell-mediated mechanisms of chronic gastritis. Chronic Helicobacter gastritis is initially localized in the antral section (early stage). With prolonged infection and as the disease progresses, the inflammatory process from the antral section spreads to the body of the stomach, atrophic changes in the gastric mucosa begin to clearly predominate, and diffuse atrophic pangastritis develops (late stage of the disease).

At this stage, Helicobacter pylori are no longer detected. This is probably due to the fact that as the gastric mucosa atrophies, glandular atrophy and transformation of the gastric epithelium into intestinal epithelium (metaplasia) develops, which lacks receptors for Helicobacter pylori adhesins.

Long-term infection of the gastric mucosa with Helicobacter pylori causes permanent damage to the gastric epithelium. As a response to this long-term damaging factor, the proliferation of cells of the gastric epithelium increases sharply, which also becomes permanent. The intensively proliferating epithelium undergoes complete maturation, the processes of proliferation prevail over the processes of maturation (differentiation) of cells.

Proliferation is enhanced by weakening the function of chalones (these intracellular hormones inhibit cell division), as well as by damage to intercellular contacts by Helicobacter. Weakening of intercellular contacts is a well-known cause of stimulation of cell division.

When Helicobacter gastritis is localized in the antral section (antral gastritis), the secretory function of the stomach is increased or normal. The increase in the acid- and pepsin-secreting function of the stomach is associated with the preservation of the main glands (in the body and fundus of the stomach), as well as with the shutdown of the mechanism for regulating the acid-forming function by the affected antral section. Normally, when the concentration of hydrogen ions reaches pH < 2 in the antral section, inhibition of gastrin secretion begins, which accordingly reduces the secretory activity of the main glands of the stomach. With antral gastritis, this regulatory process is disrupted, which leads to ongoing hyperfunction of the main glands of the stomach and hyperproduction of hydrochloric acid and pepsin.

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Pathogenesis of autoimmune gastritis

Autoimmune gastritis is observed much less frequently than Helicobacter. This variant of gastritis is characterized by a combination with B12-folate deficiency anemia, less common is a combination with Adcison's disease (chronic primary adrenal cortex insufficiency), hypoparathyroidism, autoimmune thyroiditis. With autoimmune gastritis, from the very beginning, damage to the main glands of the stomach, located in the body and fundus of the stomach, is observed. The most characteristic feature of autoimmune gastritis is the rapid development of diffuse atrophy of the gastric mucosa, which is caused by the production of autoantibodies to parietal cells and the internal factor - gastromu-coprotein.

Antibodies bind to the microvilli of the intracellular tubular system of parietal cells.

There are several types of autoantibodies against parietal cells in chronic autoimmune gastritis:

• "classical" autoantibodies against parietal cell microsomal antigens;
• cytotoxic antibodies (specific for autoimmune gastritis, Ayer, 1990);
• antibodies to gastrin-binding proteins, block receptors to gastrin;
• antibodies against H+-K+-ATPase, which provides the function of the proton pump during the secretion of hydrochloric acid.

These antibodies are found in 30% of patients with autoimmune gastritis, they block the function of the proton pump and are responsible for the development of hypo- and achylia.

Antibodies against intrinsic factor (gastromucoprotein) are of two types:

• blocking the binding of vitamin B12 to intrinsic factor;
• forming a complex with vitamin B12.

Circulating antibodies damage the fundic glands. The mechanism of this damaging action varies.

It has been established that autoantibodies can have a specific cytotoxic effect on parietal cells with the help of complement, and some parietal cell antibodies have the ability to bind complement. Thus, they participate in the destruction of the gastric mucosa. In addition, an antibody-dependent and cell-mediated cytotoxic effect appears.

Local humoral and cellular immune mechanisms play a major role in the damage of the gastric epithelium in chronic autoimmune gastritis. Peculiarities of cellular infiltration of the mucous membrane in autoimmune gastritis have been established. A sixfold increase in the content of B-lymphocytes and T-helper lymphocytes has been found in the fundus of the stomach. At the same time, the number of IgA plasma cells sharply decreases and the number of IgG plasma cells increases. Local predominance of IgG is currently regarded as a violation of local humoral immunity, providing a damaging effect on the gastric mucosa.

The causes of autoantibodies and the development of chronic autoimmune gastritis are unknown. Most researchers believe that a hereditary predisposition is necessary for the development of autoimmune processes in the gastric mucosa. Under such conditions, any, even minor, damaging effect on the gastric mucosa leads to the affected parietal cells becoming autoantigens, to which antibodies are formed. At a sufficiently high level of these antibodies (individual for each patient), they interact with the parietal cells, followed by damage and atrophy of the gastric mucosa.

Autoimmune gastritis is localized primarily and predominantly in the area of the fundus and body of the stomach; in these areas, atrophy of the mucous membrane develops with progressive loss of specialized glands and their replacement by pseudopyloric glands and intestinal epithelium (intestinal metaplasia of the mucous membrane).

The antral section retains its structure, and only superficial gastritis is found in it, which can undergo reverse development. However, in 36% of patients with B12-deficiency anemia, along with atrophic fundal gastritis, not only superficial but also atrophic pyloric gastritis can be observed.

Perhaps this is a feature of the course of chronic autoimmune gastritis. It is possible that autoimmune mechanisms can participate in the damage of the antral part of the stomach in chronic autoimmune gastritis, but antibodies against the pyloric glands have not yet been identified.

In chronic autoimmune gastritis, Helicobacter pylori infection is very rare, even rarer than in healthy people. This is due to the following circumstances:

• with autoimmune gastritis, intestinal metaplasia of the gastric epithelium occurs; Helicobacter does not develop in areas of such metaplasia;
• In autoimmune gastritis, resistance of the antral mucosa to Helicobacter develops.

A characteristic feature of the pyloric glands in patients with autoimmune gastritis is hyperplasia of gastrin-producing cells (secondary) and, naturally, hypergastrinemia.

Autoimmune gastritis in the body and fundus of the stomach is characterized by accelerated progression, especially in people over 50 years of age, as well as in the stage of severe damage to the mucous membrane. In the antral section, stabilization or even reverse development of the chronic inflammatory process is observed.

Pathogenesis of chronic gastritis caused by NSAIDs

Chronic gastritis caused by taking nonsteroidal anti-inflammatory drugs often develops in people with certain risk factors. These include old age and a history of such digestive diseases as chronic hepatitis, chronic non-calculous and calculous cholecystitis, and pancreatitis.

The mechanism of development of chronic gastritis under the influence of NSAIDs is that they block the enzyme cyclooxygenase-1, which is involved in the production of protective prostaglandins from arachidonic acid, stabilizing the cell membrane and having a cytoprotective effect in the stomach and kidneys. When treating with NSAIDs, the activity of the enzyme cyclooxygenase-1 is disrupted, which disrupts the synthesis of protective prostaglandins and creates all the necessary conditions for the development of chronic gastritis.

Pathogenesis of chronic reflux gastritis

Chronic reflux gastritis occurs as a result of duodenogastric reflux and is observed in patients who have undergone gastric resection (gastritis of the resected stomach stump), as well as in patients suffering from chronic duodenal obstruction with the development of hypertension and stasis in the duodenum.

Under these conditions, a significant amount of bile enters the stomach. Bile acids have a damaging effect on the gastric mucosa. This is also facilitated by the alkaline reaction of the gastric contents, which is usually observed in the gastric stump after resection.

Infection with Helicobacter pylori is not typical for chronic reflux gastritis. This is due to the presence of bile in the gastric contents, as well as a decrease in the amount of mucus produced by the mucous membrane, which is necessary for the functioning of Helicobacter pylori.

Common pathogenetic factors of chronic gastritis

Common to various etiological variants of chronic gastritis are disturbances in the synthesis of prostaglandins in the gastric mucosa and the function of the gastrointestinal endocrine system.

Disturbances in the synthesis of protective mediators

The gastric mucosa synthesizes so-called protective mediators - prostaglandins and growth factors (epidermal growth factor and transforming growth factor-α).

It has been established that the mucous membrane of the stomach and duodenum is capable of recovering very quickly after damage (within 15-30 minutes) due to the fact that cells move from the crypts of the gastric glands along the basal membrane and, thus, the defect in the damaged area of the epithelium is closed. The main, additional and parietal (parietal) cells produce prostaglandins E2, which protect the mucous membrane of the stomach by reducing the activity of parietal cells and, consequently, reducing the production of hydrochloric acid, stimulating the secretion of mucus and bicarbonates, increasing blood flow in the mucous membrane, reducing the reverse diffusion of H+ ions and accelerating cell renewal.

In chronic gastritis, the functioning of these protective mechanisms decreases, which naturally contributes to the progression of the disease.

Dysfunction of the gastrointestinal endocrine system

The mucous membrane of the stomach and intestines contains endocrine cells that produce hormones and hormone-like substances that have a pronounced effect on the function of the stomach and intestines.

Gastrointestinal hormones affect some links of the immune system. Thus, neurotensin stimulates the release of histamine from mast cells, chemotaxis, and phagocytosis. VIP stimulates the activity of adenylate cyclase in T-lymphocytes and suppresses the mitogenic response, lymphocyte migration, T-cell link of immunity, and lymphoblastic transformation. Bombesin activates lymphocyte migration. a-endorphin stimulates the natural killer activity of lymphocytes.

The state of the gastrointestinal system has been studied mainly in autoimmune gastritis. Hyperplasia of pyloric G-cells has been established, which correlates with high levels of gastrin in the blood, but not in the gastric mucosa.

G-cell hyperplasia is associated with the absence of the reverse inhibitory effect of hydrochloric acid (achylia is observed in atrophic autoimmune gastritis). The number of pyloric D-cells decreases, which is accompanied by a decrease in the production of somatostatin and hydrochloric acid.

Due to the multifaceted influence of the gastrointestinal endocrine system on the functional state of the stomach and the immune system, it should be considered that it plays a major role in the pathogenesis of chronic gastritis.

Pathomorphology of chronic gastritis

The most characteristic manifestation of chronic gastritis is the infiltration of the proper layer of the gastric mucosa by mononuclear cells-lymphocytes and plasma cells, as well as neutrophilic leukocytes and eosinophils.

The higher the activity of inflammation of the gastric mucosa, the more pronounced the cellular infiltration.

The next characteristic feature of chronic gastritis is atrophy, a progressive reduction and disappearance of the main (pepsin-forming) and parietal (acid-forming) cells. These highly specialized cells are replaced by cells that produce large amounts of mucus (intestinal metaplasia). At the same time, the process of regeneration of the gastric mucosa is disrupted, especially the differentiation and maturation of specialized stomach cells (main and parietal). Helicobacter colonization does not occur in areas of intestinal metaplasia.

Symptoms chronic gastritis

Chronic gastritis caused by H. pylori infection is asymptomatic. Dyspepsia syndrome associated with chronic Helicobacter gastritis should be regarded as a manifestation of functional dyspepsia.

Chronic autoimmune gastritis is observed mainly in middle and old age. It is often combined with pernicious anemia, thyroiditis, thyrotoxicosis, primary hypoparathyroidism. The anamnesis and symptoms found during examination are mainly due to these diseases.

Usually autoimmune gastritis is characterized by a feeling of heaviness in the epigastric region after eating, a feeling of overeating, and a full stomach. Patients are bothered by belching food and air, and an unpleasant taste in the mouth. Appetite is reduced. Flatulence and unstable stool are possible.

Symptoms of chronic Helicobacter gastritis

Symptoms of chronic Helicobacter gastritis depend on the stage of the disease. For the early stage of the disease (more often observed in people, mainly young people), localization in the antral part of the stomach is characteristic, and non-atrophic antral gastritis without secretory insufficiency develops.

It is characterized by ulcer-like symptoms:

• periodic pain in the epigastrium 1.5-2 hours after eating;
• often hunger pains (early in the morning, on an empty stomach);
• heartburn; sour belching;
• normal appetite;
• tendency to constipation.

As the disease progresses, the inflammatory process spreads to the remaining parts of the stomach and becomes diffuse in nature with atrophy of the gastric mucosa and secretory insufficiency. In this case, Helicobacter pylori are not detected as often and not in such large quantities as in the early antral form of chronic gastritis.

In the late stage, the subjective symptoms of chronic Helicobacter gastritis correspond to the well-known clinical picture of chronic gastritis with secretory insufficiency:

• poor appetite; sometimes nausea;
• a feeling of metallic taste and dry mouth;
• belching of air, food, sometimes rotten;
• a feeling of heaviness in the epigastrium and fullness after eating;
• dull, non-intensive pain in the epigastrium after eating;
• rumbling and bloating;
• a tendency to frequent and loose stools.

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Chronic autoimmune gastritis

Chronic autoimmune gastritis is characterized by atrophy of the gastric mucosa and secretory insufficiency.

It is very rare, occurring in less than 1% of the population. Its characteristic feature is localization in the fundus of the stomach, while the pyloric section remains virtually unaffected or changes insignificantly. This leads to a sharp decrease in the secretion of hydrochloric acid, pepsinogen, and intrinsic factor (gastromucoprotein). Deficiency of gastromucoprotein leads to impaired absorption of vitamin B12 and the development of B12-deficiency anemia.

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Granulomatous gastritis

Granulomatous gastritis develops with Crohn's disease, sarcoidosis, tuberculosis, and mycosis of the stomach. Its morphological picture is described above. The clinical picture is dominated by the symptoms of the underlying disease. Manifestations of gastritis itself are expressed in dyspepsia, sometimes vomiting, in some patients - bloody.

Eosinophilic gastritis

Eosinophilic gastritis is a rare disease. It is most often observed in systemic vasculitis, sometimes in food allergies, bronchial asthma, eczema.

A characteristic pathological feature of the disease is the infiltration of the gastric mucosa, and sometimes other layers of the stomach wall, by a large number of eosinophils. Eosinophilia may develop. There are no specific gastroenterological manifestations.

The clinical picture of eosinophilic gastritis corresponds to the clinical picture of chronic gastritis with normal secretory function of the stomach.

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Lymphocytic gastritis

Lymphocytic gastritis is characterized by pronounced lymphocytic infiltration of the gastric epithelium, thickened folds, nodules and erosions.

Lymphocytic gastritis has a characteristic localization. In 76% it is pangastritis, in 18% of cases it is fundal gastritis and in 6% it is antral gastritis.

According to Whitehead (1990), there are two forms of chronic lymphocytic gastritis - with acute and chronic erosions.

Many gastroenterologists believe that Helicobacter pylori infection plays a role in the origin of lymphocytic gastritis. However, this is not a generally accepted point of view.

The clinical course of lymphocytic gastritis is similar to the early stage of chronic Helicobacter gastritis (with normal or increased secretory function).

Hypertrophic gastritis (Menetrier's disease)

The main characteristic morphological sign of hypertrophic gastritis is pronounced hypertrophy of the gastric mucosa in the form of giant folds covered with a large amount of viscous mucus.

Histological examination of gastric mucosa biopsies reveals a sharp thickening, lengthening and widening of the gastric pits. In the epithelial layer, signs of transformation into intestinal epithelium are found, as well as cysts. Erosions and hemorrhages may be detected.

The main clinical manifestations of hypertrophic gastritis are:

• pain in the epigastrium, often very intense, occurring soon after eating;
• heartburn;
• belching of air, food;
• frequent vomiting with blood;
• anorexia;
• weight loss;
• swelling of the feet and hands;
• diarrhea;
• hypoproteinemia;
• increase or decrease in the secretion of hydrochloric acid;
• possible combination with duodenal ulcer.

Hypertrophic folds of the mucous membrane should be differentiated from gastric lymphoma.

Chronic polypous gastritis

Polyps are a consequence of dysregenerative hyperplasia of the gastric mucosa.

Chronic polypous gastritis is characterized by the same clinical manifestations as chronic gastritis with secretory insufficiency. Sometimes gastric bleeding is observed. X-ray examination of the stomach reveals small homogeneous filling defects, the relief of the mucous membrane is unchanged; gastroscopic examination reveals multiple small polyps, which are located mainly in the antral part of the stomach.

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Forms

There are two main forms of chronic gastritis:

1. Chronic autoimmune gastritis (5% of all cases of chronic gastritis) is associated with the formation of antibodies to the parietal cells of the stomach and the intrinsic factor of Castle. Its characteristic feature is the primary development of atrophic changes (inflammation combined with thinning of the mucous membrane, loss of glands, metaplasia of the epithelium) of the mucous membrane of the fundus of the stomach.
2. Chronic gastritis caused by Helicobacter pylori infection (95% of all cases of chronic gastritis). Structural changes in the gastric mucosa develop in all infected individuals.

Chronic gastritis can be active (the inflammatory infiltrate contains mononuclear cells and neutrophils) and inactive (there are only mononuclear cells - lymphocytes, plasma cells and macrophages), and also accompanied by intestinal metaplasia (develops in all parts of the stomach) or pseudopyloric metaplasia, which is the replacement of the glands of the fundus with mucus-forming glands of the pyloric section.

In 1990, the Sydney classification of chronic gastritis was proposed. It takes into account morphological changes in the gastric mucosa (degree of inflammation activity, severity of atrophy and metaplasia of epithelial cells, presence of Helicobacter pylori seeding of the gastric mucosa), topography (prevalence) of the lesion (antral gastritis, gastritis of the body of the stomach, pangastritis), etiology of the disease (gastritis associated with Helicobacter pylori, autoimmune gastritis, idiopathic gastritis) and, in addition, suggests the allocation of special forms of chronic gastritis (granulomatous, eosinophilic, lymphocytic and reactive). The Sydney classification of chronic gastritis also contains an endoscopic section, reflecting, along with other characteristics, the presence of erosions of the gastric mucosa and subepithelial hemorrhages.

The latest classification of chronic gastritis was proposed in 1994 and was called the Houston classification. This classification identifies the following variants of the disease:

• Non-atrophic gastritis (synonyms: superficial, diffuse antral, interstitial, hypersecretory, type B);
• Atrophic gastritis:
  • autoimmune (synonyms: type A, diffuse body of the stomach,
  • associated with pernicious anemia),
  • multifocal (occurs in countries with a high incidence of stomach cancer);
• Special forms of chronic gastritis:
  • chemical (synonyms: reactive reflux gastritis, type C),
  • radiation,
  • lymphocytic (synonyms: varioliform, associated with celiac disease),
  • non-infectious granulomatous (synonym - isolated granulomatosis),
  • eosinophilic (synonym - allergic),
  • other infectious forms caused by various microorganisms, excluding Helicobacter pylori.

The working group members point out that the diagnosis of chronic gastritis should be primarily descriptive, and then, if possible, etiologic factors are added to it.

The classification identifies the following morphological variants of changes in the mucous membrane:

1. Normal mucous membrane.
2. Acute gastritis.
3. Chronic gastritis - with the allocation of 4 degrees depending on the severity of infiltration by lymphocytes and plasma cells (minimal, slight, moderate and severe).
4. Intestinal metaplasia types 3.
   1. Type 1 - complete or small bowel.
   2. Type 2 - incomplete: goblet cells among the superficial epithelium of the stomach.
   3. Type 3 - incomplete metaplasia of the small intestinal type with secretion of sulfomucins.

A distinction is also made between focal and widespread metaplasia.

Morphological manifestations of special forms of chronic gastritis are as follows.

• Granulomatous gastritis is characterized by the presence of epithelial cell granulomas, sometimes with an admixture of giant multinucleated cells in the proper plate of the mucous membrane. Granulomatous gastritis is found in sarcoidosis, Crohn's disease, mycoses, tuberculosis and foreign bodies. Granulomatous gastritis can be isolated, idiopathic (of unknown etiology).
• Eosinophilic gastritis is characterized by pronounced eosinophilic infiltration of not only the gastric mucosa, but also other layers of its wall. Eosinophilic infiltration is combined with edema and plethora. The etiology of this type of gastritis is unknown. According to research, 25% of patients have a history of allergies, bronchial asthma, eczema, and hypersensitivity to food proteins. Sometimes the disease is a manifestation of eosinophilic gastroenteritis, which can develop at any age, with damage to the mucous membrane of the small intestine accompanied by the development of malabsorption syndrome, damage to the muscle layers - fibrosis and intestinal obstruction, and the serous membrane - ascites.

In eosinophilic gastritis, the antral region is predominantly affected; along with eosinophils, polymorphonuclear leukocytes, lymphocytes, macrophages, IgE, and plasma cells are found.

• Lymphocytic gastritis is characterized by selective, pronounced lymphocytic infiltration of the gastric epithelium; there are relatively few lymphocytes and plasma cells in the lamina propria. Lymphocytic gastritis can be considered when the number of lymphocytes exceeds 30:100 epithelial cells.

Endoscopic examination reveals nodules, thickened folds, and erosions.

The etiology and pathogenesis of this form of gastritis are unknown.

It is assumed that the immune response to the local effect of some antigen on the gastric mucosa plays the main role in the development of chronic lymphocytic gastritis (the influence of Helicobacter infection is not excluded, gluten intolerance is also assumed). A characteristic feature of chronic lymphocytic gastritis is erosion of the gastric mucosa.

When describing morphological changes in the gastric mucosa in chronic gastritis, the intensity of inflammation, activity of the process, atrophy, intestinal metaplasia and severity of Helicobacter colonization are assessed. These main morphological changes are assessed semi-quantitatively as weak, moderate and severe. Non-specific and specific non-variable changes are also distinguished (they are simply described, but the degree of expression is not taken into account).

Non-specific changes include such as mucus content, epithelial dystrophy, edema, erosion, fibrosis, vascularization. Specific non-variable changes refer to one of the specific (special) types of gastritis (granulomatous, lymphocytic, eosinophilic, reactive).

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Endoscopic classification section

The endoscopic section of the classification also reflects the localization of changes in the gastric mucosa (antrum gastritis, body gastritis, pangastritis) and offers the following terms to describe the changes: edema; hyperemia (erythema); loosening; exudation; erosion (flat, raised); nodularity; hyperplasia of folds; visibility of vascular reaction; intramural hemorrhages; duodenogastric reflux. All these descriptive signs of chronic gastritis revealed by endoscopy can have a semi-quantitative assessment (severity - mild, moderate, severe).

Based on these descriptive features, the following endoscopic categories of gastritis are defined:

• erythematous-exudative (commonly known as “superficial” gastritis);
• atrophic gastritis;
• hemorrhagic gastritis;
• hyperplastic gastritis.

The authors of the classification provide approximate formulations of histological conclusions: “autoimmune chronic pangastritis with prevalence of severe atrophy in the fundus”; “associated with Helicobacter infection antral chronic gastritis of moderate activity”, “reactive antral gastritis associated with bile”, “reactive antral gastritis with erosions associated with non-steroidal anti-inflammatory drugs”.

The Sydney and Houston classifications of chronic gastritis do not include the section “State of the secretory function of the stomach”, which is very important from a practical point of view.

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Diagnostics chronic gastritis

With antral Helicobacter gastritis (early stage), the following characteristic symptoms are revealed:

• the tongue is clean or slightly coated at the root;
• local pain in the pyloroduodenal zone (in the epigastrium, mainly on the right);
• the lower border of the stomach, determined by the splashing sound, is located normally (3-4 cm above the navel);
• In case of severe exacerbation of antral gastritis, slight weight loss is possible.

In the diffuse form of chronic Helicobacter gastritis (late stage), an objective examination reveals the following symptoms (picture of chronic gastritis with secretory insufficiency):

• weight loss (usually with prolonged disease, development of secondary enteric syndrome and decreased exocrine function of the pancreas);
• the tongue is thickly coated;
• cracks in the corners of the mouth;
• moderate diffuse pain in the epigastric region;
• the lower border of the stomach, determined by the splashing sound, is located below the normal level (at the level of the navel or below);
• Often, rumbling is detected during palpation of the large intestine, and significant flatulence may be detected.

Laboratory diagnostics

As part of a general clinical examination: clinical blood test, clinical urine test, clinical stool test, stool test for occult blood, determination of blood type and Rh factor. Changes in laboratory parameters are not typical for chronic gastritis. In the case of atrophic gastritis combined with B12-deficiency anemia, a decrease in hemoglobin content, an increase in the color index of erythrocytes, and the appearance of megakaryotypes are possible.

Biochemical blood tests: total protein, albumin, cholesterol, glucose, bilirubin, transaminases, amylase, serum iron.

Detection of H. pylori infection is carried out using invasive (rapid urease test, morphological methods) or non-invasive [breath test, determination of antibodies (AT) to H. pylori] methods.

[ 71 ], [ 72 ], [ 73 ], [ 74 ], [ 75 ], [ 76 ]

Additional laboratory tests

• Study of antibodies to gastric parietal cells - detection of antibodies is typical for chronic autoimmune gastritis, however, in some patients infected with H. pylori, antibodies to gastric parietal cells are also detected in the blood serum.
• Study of the level of pepsinogen I - a decrease below the threshold value indicates atrophy of the body of the stomach.

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Instrumental research

• Mandatory instrumental studies

FEGDS is the main method of confirming the diagnosis, since it allows for a histological examination of the biopsy. Histological examination of biopsy samples of the mucous membrane of the fundus and antrum of the stomach is performed to determine the type of pathomorphological changes and to clarify the type of gastritis, and if it is impossible to perform non-invasive tests to detect H. pylori, to examine the biopsy samples for its presence.

Ultrasound examination (US) of the liver, pancreas, gallbladder - for the diagnosis of concomitant pathology of the organs of the hepatobiliary system and pancreas.

X-ray, gastroscopic and histological examinations

Diagnosis of Helicobacter pylori infection

• Cytological examination

For cytological examination, smears-imprints of biopsy specimens of the gastric mucosa (antral section) are used during gastroscopy. The biopsy specimen must be taken from areas with the greatest hyperemia and edema, but not from the bottom of erosions or ulcers. Then the smears are dried and stained using the Romanovsky-Giemsa method. Helicobacteria are located in the mucus, have a spiral, curved shape, and can be S-shaped.

There are three degrees of contamination with Helicobacter:

• weak (+) - up to 20 microbial bodies in the field of view;
• average (++) - up to 50 microbial bodies in the field of view;
• high (+++) - more than 50 microbial bodies in the field of view.

The microscope magnification used is x360.

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Urease test

The urease test for Helicobacter pylori detection is based on the following principle.

Helicobacteria secrete the enzyme urease, under the influence of which urea contained in the stomach decomposes with the release of ammonium:

The ammonium ion formed as a result of the reaction significantly increases the pH of the medium, which can be determined using an indicator, and, therefore, can be noted visually by a change in its color.

To detect Helicobacter infection, the express urease method is used. The express kit contains urea, a bacteriostatic agent and phenol-rot as a pH indicator (the indicator changes color from yellow to crimson when the reaction shifts to the alkaline side).

A biopsy of the gastric mucosa obtained during gastroscopy is placed in the express kit medium.

If there are Helicobacter pylori in the biopsy, the medium acquires a crimson color. The time of appearance of the crimson color indirectly indicates the number of Helicobacter pylori.

• (+) - minor infection (crimson coloration by the end of the day);
• (++) - moderate infection (crimson coloration within 2 hours);
• (+++) - significant infection (crimson coloration appears within the first hour);
• (-) - the result is negative (crimson coloration occurs later than after 24 hours).

Foreign companies produce test systems for detecting Helicobacter by the urease method (de-nol test from Yamanouchi, CLO test - Australia, etc.).

C-urea breath test

The method is based on the fact that 13C-labeled urea taken orally decomposes under the influence of Helicobacter urease to form ammonia and CO2. The content of 13C is determined in exhaled CO2, and its level is used to draw a conclusion about Helicobacter infection.

The study is conducted on an empty stomach. First, two background samples of exhaled air are taken in plastic tubes at 1-minute intervals. Then the patient takes a light test breakfast (milk, juice) and a test substrate (an aqueous solution of urea labeled with 13C). Then, over the course of 1 hour, 4 samples of exhaled air are taken at 15-minute intervals.

The content of 13C in exhaled air is determined using a mass spectrometer. Depending on the percentage of the isotope 13C in exhaled air, there are 4 degrees of Helicobacter infection:

• less than 3.5% - light;
• 3.5-6.4% - average;
• 6.5-9.4% - heavy;
• more than 9.5% - extremely severe.

Normally, the content of 13C in exhaled air does not exceed 1% of the total amount of CO2.

The method is extremely expensive and is not yet widely available.

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Microbiological method

Helicobacter cultures are made from biopsies of the gastric mucosa. The cultures are incubated in microaerophilic conditions with an oxygen content of no more than 5%. Special gas-generating chemical packages are used to create such an environment. Special blood nutrient media are used for the growth of Helicobacter. After 3-5 days, small, round, transparent, dew-shaped colonies of Helicobacter appear on the nutrient medium. The isolated culture is then identified.

Histological method

The material used is biopsy samples of the gastric mucosa in areas of the most severe inflammation.

Thin sections are prepared and the preparations are stained with hematoxylin and eosin or by the Romanovsky-Giemsa method. Helicobacteria are detected as spiral-shaped, S-shaped bacteria.

In recent years, more accurate methods for identifying Helicobacter have emerged. These include the immunochemical method with monoclonal antibodies. Currently, there are commercial kits that allow the use of conventional biopsy material fixed in formalin and embedded in paraffin. The monoclonal antibodies included in these kits work at a dilution of 1:200,000 and selectively stain only Helicobacter.

Recently, methods for detecting Helicobacter pylori using DNA hybridization in conventional paraffin sections have begun to be used.

Immunological methods

Three to four weeks after infection of the mucous membrane of the stomach and duodenum with Helicobacter, antibodies to Helicobacter appear in the blood of patients. These antibodies are determined by the enzyme immunoassay method.

This method detects IgG, IgA, IgM class antibodies in the blood and secretory IgA, IgM in saliva and gastric juice.

The test remains positive for one month after successful eradication of Helicobacter.

Study of gastric secretory function

In chronic Helicobacter gastritis, the secretory function of the stomach may be altered, but the severity of the changes depends on the stage of gastritis. In antral gastritis (early stage of Helicobacter gastritis), the acid-forming and pepsin-forming functions are normal or often increased, in pangastritis (late stage) - decreased, but achlorhydria, as a rule, does not occur.

Currently, there are three main methods for determining the acid-forming function of the stomach:

• intragastric pH-metry;
• fractional examination of gastric juice using a thin probe with the use of gastric secretion stimulants;
• probeless methods - determination of acidity using ion-exchange resins ("Acidotest"). Probeless methods are uninformative and are rarely used at present.

Fractional study of gastric juice

The method allows to study gastric secretion over a long period of time, and also to obtain an idea of its nature in the complex reflex phase (response to a mechanical stimulus in the stomach - gastric tube) and the neurohumoral phase (reaction to an enteral or parenteral stimulus). In this regard, two stages of fractional gastric probing are distinguished:

• determination of basal secretion;
• determination of sequential (stimulated) secretion.

The first stage - determination of basal secretion - is carried out as follows. In the morning on an empty stomach, a thin probe is inserted into the patient's stomach, all the contents of the stomach are removed, and then gastric juice is aspirated every 15 minutes for an hour.

The total volume of these portions in ml represents the volume of basal secretion of gastric juice. The content of total and free hydrochloric acid and pepsin is also determined in each portion.

The second stage - sequential stimulated secretion - is the determination of the secretory function of the stomach every 15 minutes after the subcutaneous administration of histamine (it stimulates gastric secretion). To avoid the side effects of histamine, the patient is preliminarily administered 2 ml of a 2% solution of suprastin (after receiving the 3rd portion of basal secretion, i.e. 30 minutes before the beginning of the second stage of the study of gastric secretion). After the administration of histamine, gastric juice is collected every 15 minutes for 1 hour.

A distinction is made between submaximal and maximal histamine tests. For submaximal stimulation, histamine is administered at a dose of 0.008 mg/kg of body weight, for maximal stimulation - 0.025 mg/kg of body weight. The maximal histamine test is rarely used due to its pronounced side effects.

Widely used as a stimulant of gastric secretion are also pentagastrin or tetragastrin in a dose of 6 mg/kg of body weight. Gastrin preparations are well tolerated and are preferable to histamine. Other stimulants of gastric secretion - the so-called pre-oral breakfasts are rarely used (breakfast according to Leporsky - 200 ml of cabbage juice; according to Petrova - 300 ml of 7% cabbage broth; according to Zimnitsky - 300 ml of meat broth; according to Erman - 300 ml of 5% alcohol solution; according to Kach and Kalk - 0.5 g of caffeine per 300 ml of water).

The following indicators of gastric secretion are determined:

• volume of juice on an empty stomach;
• volume of juice during the hour before stimulation (basal secretion);
• volume of juice within an hour after stimulation with histamine or pentagastrin;
• total acidity, free hydrochloric acid and pepsin content;
• pH of gastric juice.

The production of hydrochloric acid is calculated per 1 hour (flow rate) and expressed in meq/h or mg/h.

After the use of histamine, the secretory effect begins after 7-10 minutes, reaches its maximum after 20-30 minutes and lasts for about 1-1.5 hours. Pentagastrin acts in approximately the same way.

Intragastric pH-metry

The method of intragastric pH-metry is based on the determination of the concentration of free hydrogen ions in the gastric contents, which allows us to draw a conclusion about the acid-forming function of the stomach. Intragastric pH-metry has a number of advantages over the above-mentioned fractional aspiration-titration method:

• when studying the acidity of gastric juice, indicator reagents with low sensitivity are used for testing, therefore sometimes a condition assessed as anacidic does not actually correspond to it. The pH-metry method is free from this drawback;
• Unlike the aspiration-titration method, pH-metry allows one to judge the acid-forming function in patients with a resected stomach, and also allows one to diagnose the reflux of acidic stomach contents into the esophagus (gastroesophageal reflux).

Intragastric pH-metry is performed using the Gastroscan-24 complex (RF), which allows one to determine the pH in the esophagus, stomach and duodenum during the day, and to study the effect of various medications on the acid-forming function of the stomach.

According to A. S. Loginov (1986), the pH of the gastric contents in the body of the stomach is 1.3-1.7 (normaciditas); pH within 1.7-3.0 indicates a hypoacid state; pH over 3.0 indicates an anacid state; pH values < 1.3 are characteristic of a hyperacid state.

In the pyloric region, with normal acid-forming function of the stomach, pH < 2.5.

When identifying an anacid state, it is important to determine its nature - whether it is true achlorhydria (caused by atrophy of the gastric mucosa) or false (caused by inhibition of acid formation). To do this, determine the pH of the gastric contents after maximum stimulation with histamine or pentagastrin. Preservation of the anacid state after maximum stimulation indicates true achlorhydria.

Non-probe methods for studying the secretory function of the stomach

Non-probe methods of studying the secretory function of the stomach are uninformative and allow only a rough estimate of it. These methods are used in situations where gastric probing is contraindicated: decompensated defects; coronary heart disease; hypertension; aortic aneurysm; esophageal stenosis; lung diseases with respiratory failure, etc.

Desmoid test. Salts is based on the ability of gastric juice to digest catgut. The patient swallows a bag of methylene blue covered with catgut on an empty stomach. After this, urine is collected after 3, 5, 20 hours. Intensive coloring of all three portions indicates a hyperacid state, the second and third - normal acidity; coloring of only one portion of urine indicates achlorhydria.

The ion-exchange resin method is based on the ability of indicator ions (a low-molecular compound bound to an ion-exchange resin) to exchange in the stomach for the same amount of hydrochloric acid hydrogen ions. In this case, the indicator is released from the resin, absorbed in the intestine and excreted in the urine, where it is detected.

Determination of uropepsin in urine indirectly allows to judge the enzyme-forming function of the stomach (peptic activity of gastric juice). Normally, 0.4-1.0 mg of uropepsin is excreted with urine per day.

General, biochemical, immunological blood tests

No significant changes in general, biochemical, or immunological blood tests were observed in patients with chronic Helicobacter gastritis.

Diagnosis of chronic autoimmune gastritis

Chronic gastritis, the morphological substrate of which is inflammation of the gastric mucosa, occurs without any clinical manifestations. The diagnosis of chronic gastritis should be based not on the clinical picture, but on the results of laboratory and instrumental studies (primarily morphological examination of the gastric mucosa).

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Objective examination of patients

The general condition is satisfactory, but with pronounced atrophy of the gastric mucosa and achlorhydria, digestion in the small intestine is significantly impaired and the following characteristic symptoms appear:

• weight loss;
• dry skin, sometimes its darkening due to the development of hypocorticism (the skin is pigmented in the area of the nipples, face, palmar folds, neck, genitals);
• pale skin (due to anemia);
• signs of polyvitaminosis (vitamin A deficiency - dry skin, deterioration of vision; vitamin C deficiency - bleeding and loosening of the gums; vitamin B2 deficiency - cracks in the corners of the mouth; vitamin PP deficiency - dermatitis; diarrhea);
• hair loss, brittle nails;
• a decrease in blood pressure is possible (due to hypocorticism), dystrophic changes in the myocardium may appear;
• tongue coated;
• diffuse pain in the epigastric region;
• with the development of intestinal dyspepsia, pain and rumbling upon palpation of the umbilical and ileocecal region;
• prolapse of the greater curvature of the stomach may be determined.

X-ray, gastroscopic and histological examinations

X-ray examination of the stomach reveals a decrease in the severity of the folds of the gastric mucosa.

Gastroscopy reveals the following characteristic changes:

• the folds of the mucous membrane are significantly lower than normal; in advanced cases of atrophy, they may be absent altogether;
• the gastric mucosa is thinned, atrophic, pale, and the vascular pattern is clearly visible through it;
• Often you can see an excess amount of mucus, which is associated with an increase in the number of mucus-forming cells;
• the pylorus gapes, the contents of the stomach are dumped into the duodenum, gastric peristalsis is sluggish, mucus is retained on the walls of the stomach;
• the antral part of the stomach is practically unchanged in autoimmune gastritis;
• Very rarely, with autoimmune gastritis, erosions of the mucous membrane can be seen; in this case, a combination of Helicobacter and autoimmune gastritis can be assumed, and it is necessary to conduct a biopsy study for the presence of Helicobacter.

Histological examination of the fundus of the stomach reveals atrophy of the gastric mucosa with progressive loss of specialized glands and their replacement by pseudopyloric glands and intestinal epithelium. The antral section, unlike chronic Helicobacter gastritis, retains its structure, but the histological picture of superficial gastritis is determined, which has a tendency to reverse development. According to research data, antral gastritis is combined with atrophic fundus gastritis in 36% of patients with B12-deficiency anemia, and it can also be atrophic in some patients. Perhaps this is due to the autoimmune nature of the pyloric lesion, since its mucous membrane is very resistant to colonization by Helicobacter.

A characteristic feature of chronic autoimmune gastritis is hyperplasia of gastrin-producing cells of the pyloric glands.

L. I. Aruin points out the specific features of mononuclear infiltration for chronic autoimmune gastritis:

• sixfold increase in the content of B-lymphocytes and T-helpers;
• a sharp decrease in the number of IgA plasma cells and a significant increase in the number of IgG plasma cells.

Local predominance of IgG indicates the predominant involvement of local humoral immune mechanisms.

Autoimmune gastritis in the fundus with severe damage to the gastric mucosa and in patients over 50 years of age acquires a tendency to rapid progression. In the antral section, on the contrary, stabilization is observed and even reverse development of the inflammatory process is possible with the disappearance of round-cell inflammatory infiltration.

Studies indicate that in the body of the stomach with autoimmune gastritis, over time, inflammatory infiltration also decreases and atrophy of the gastric mucosa begins to acquire a dominant role.

State of gastric secretory function

The same methods as described above (in the section on chronic Helicobacter gastritis) are used to study the secretory function of the stomach in patients with chronic autoimmune gastritis. Chronic autoimmune gastritis is characterized by a sharp decrease in the acid- and pepsin-forming function, and achlorhydria in the most severe cases of the disease.

Immunological blood test

In patients with autoimmune gastritis, autoantibodies to parietal cells and gastromucoprotein are regularly detected in the blood. Autoantibodies to the microsomal fraction of parietal cells are specific for autoimmune chronic gastritis. Antibodies to gastromucoprotein block the binding of vitamin B12 to gastromucoprotein, and the formation of antibodies to vitamin B12 is also possible.

Antibodies to gastrin-binding proteins are also detected; they block gastrin receptors. In 1/3 of patients with autoimmune gastritis, antibodies to H+K-ATPase, which provides the function of the proton pump during the secretion of hydrochloric acid, are detected. These antibodies play a leading role in the development of hypo- and achlorhydria.

In some cases of chronic autoimmune gastritis, there is a decrease in the content of suppressor T-lymphocytes in the blood, an increase in helper T-lymphocytes and immunoglobulins, and the appearance of circulating immune complexes in the blood.

General and biochemical blood analysis

With the development of B12-deficiency anemia, a decrease in the content of hemoglobin and red blood cells, an increase in the color index, leukopenia, and thrombocytopenia are observed.

A biochemical blood test is characterized by hyperbilirubinemia, moderately expressed (with the development of hemolysis in patients with B12-deficiency anemia), and an increase in the content of gamma globulins in the blood.

Differential diagnosis

In addition to chronic gastritis, so-called functional disorders of the stomach are also distinguished (differential diagnosis is extremely difficult, since this requires multiple biopsies and a whole range of other laboratory and instrumental studies).

Chronic atrophic gastritis should be differentiated from gastric ulcer with reduced secretory function, benign and malignant tumors of the stomach. The most important task is differential diagnosis with gastric cancer. Difficulties arise with endophytic tumor growth. For correct diagnosis, a comprehensive X-ray endoscopic examination with multiple targeted biopsy from the most altered areas of the mucous membrane is used. In unclear cases, dynamic observation is carried out with repeated FEGDS with biopsy. In these cases, endoscopic ultrasound is effective.

Indications for specialist consultation

• Oncologist - if stomach cancer is detected.
• Hematologist - if it is necessary to clarify the diagnosis of concomitant anemia in the context of chronic autoimmune gastritis.

Treatment chronic gastritis

The goals of treatment of chronic gastritis are to prevent the development of precancerous changes in the gastric mucosa - intestinal metaplasia and dysplasia of the mucosa.

Criteria for assessing the effectiveness of therapy: eradication of H. pylori, reduction in signs of gastritis activity, absence of progression of atrophic changes.

Indications for hospitalization

Chronic gastritis is not an indication for hospitalization. Hospitalization is indicated only if a complex examination is necessary and there are difficulties in differential diagnosis. In autoimmune gastritis, hospitalization is necessary due to B12-deficiency anemia.

Mode

It is advisable to stop smoking, as a correlation has been found between smoking and the severity of intestinal-type metaplasia of the gastric mucosa. Drugs that have an adverse effect on the gastric mucosa (e.g., NSAIDs) should be discontinued.

Diet

It has no independent value as a therapeutic measure for chronic gastritis.

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Drug therapy for chronic gastritis

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Chronic non-atrophic gastritis

Eradication of H. pylori when detected. Eradication is indicated for patients with a hereditary predisposition to gastric cancer or who require NSAIDs. The use of antisecretory drugs, prokinetics and drugs with a cytoprotective effect (sucralfate, colloidal bismuth subcitrate) is advisable in the case of functional dyspepsia syndrome against the background of chronic gastritis.

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Chronic atrophic gastritis

• If the etiological role of H. pylori is identified, eradication therapy is used.
• Treatment of B12 deficiency anemia.

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Further management of the patient

Of fundamental importance is the diagnosis of the result of eradication therapy of H. pylori, in connection with which 4-8 weeks after this course of treatment it is necessary to conduct an examination for the presence of H. pylori. Patients with atrophy of the body of the stomach or the body of the stomach and antrum, especially with the presence of precancerous changes in the mucous membrane, are subject to dispensary observation with endoscopic examination with histological assessment of biopsy samples of the mucous membrane once every 1-2 years.

Patient education

The patient should be advised to avoid taking NSAIDs. The patient should be convinced of the need to strictly adhere to the recommended regimen of taking medications, despite the fact that in some cases the amount of drugs may seem excessive to the patient.

The patient should be informed about possible complications of chronic gastritis and their clinical manifestations (peptic ulcer, stomach cancer). If there is a possibility of pernicious anemia, the patient (or his relatives, especially if the patient is elderly and senile) should know its main clinical manifestations in order to consult a doctor in a timely manner.

Prevention

Prevention of chronic gastritis has not been developed.

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Forecast

The prognosis of chronic gastritis is usually favorable. Precancerous changes in the mucous membrane (intestinal metaplasia and dysplasia) against the background of atrophic gastritis are dangerous. Timely treatment of pernicious anemia developing with chronic atrophic autoimmune gastritis in the vast majority of cases allows preventing an unfavorable development of events for the patient.

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