Chronic cholecystitis: pathogenesis

The microflora in the gallbladder is found in chronic cholecystitis only in 33-35% of cases. In most cases (50-70%), gallbladder bile in chronic cholecystitis is sterile. This is explained by the fact that bile has bacteriostatic properties (bile can normally develop only typhoid bacillus), as well as bactericidal ability of the liver (with normally functioning hepatic tissue, microbes that get into the liver by hematogenous or lymphogenous pathway die). The presence of bacteria in the gall bladder is not yet an absolute proof of their role in the etiology of chronic cholecystitis (simple bacteriocholia is possible, more important is the penetration of microflora into the wall of the gallbladder, which is indicative of the undoubted role of infection in the development of chronic cholecystitis.

Consequently, one penetration of the infection into the gallbladder for the development of chronic cholecystitis is not enough. Microbial inflammation of the gallbladder develops only when the infection of bile occurs against the background of stagnation of bile, changes in its properties (discololia), disruption of the gallbladder wall, and reduction of the protective properties of immunity.

Based on the above, the main pathogenetic factors of chronic cholecystitis can be considered the following:

• Neurodystrophic changes in the wall of the gallbladder

The development of neurodystrophic changes in the gallbladder wall is promoted by dyskinesia of the bile ducts, which accompany almost every case of chronic cholecystitis. According to some researchers, even with dyskinesia of the gallbladder morphological changes appear in its wall: first the receptor apparatus of nerve cells and the neurons themselves, then the mucosa and the muscle layer of the gallbladder, ie, a picture of neurogenic dystrophy is observed. In turn, neurogenic dystrophic changes, on the one hand, form the basis for the development of "aseptic inflammation", on the other hand create favorable conditions for the penetration of infection into the wall of the bladder and the development of infectious inflammation.

• Neuroendocrine disorders

Neuroendocrine disorders include disturbances in the function of the autonomic nervous system and the endocrine system, including gastrointestinal disorders. These disorders, on the one hand, cause the development of dyskinesia bile excretion system, on the other - contribute to stagnation of bile and dystrophic changes in the wall of the gallbladder.

In physiological conditions, sympathetic and parasympathetic innervation has a synergistic effect on the motor function of the gallbladder, which favors the flow of bile from the gallbladder into the intestine.

An increase in the tone of the vagus nerve leads to a spasmodic contraction of the gallbladder, a relaxation of the sphincter of Oddi, i.e., to the emptying of the gallbladder. The sympathetic nervous system causes a relaxation of the gallbladder and increases the tone of the sphincter of Oddi, which leads to the accumulation of bile in the bladder.

With dysfunction of the autonomic nervous system, the principle of synergism is broken, dyskinesia of the gallbladder develops, bile flow obstructs. Hyperactivity of the sympathetic nervous system contributes to the development of hypotonic, and hypertension of the vagus nerve - hypertonic dyskinesia of the gallbladder.

Reduction and emptying of the gallbladder are also carried out with the help of the diaphragmatic nerve.

• Congestion and biliary discoloration

Dyskinesia of bile ducts mainly of hypomotor type, chronic disturbance of duodenal patency and duodenal hypertension, as well as other factors, lead to stagnation of bile, which is of great pathogenetic importance. With bile stasis, its bacteriostatic properties and the stability of the gall bladder mucosa to a pathogenic flora are reduced, neurodystrophic changes in the wall of the gallbladder are aggravated, which reduces its resistance. Chronic cholecystitis also changes the physicochemical properties of bile and its composition (discholia): the colloidal balance of bile in the bladder is disrupted, the content of phospholipids, lipid complex, protein, bile acids in it decreases, bilirubin content increases, and pH changes.

These changes contribute to the maintenance of the inflammatory process in the gallbladder and predispose to stone formation.

• Disturbance of the wall of the gallbladder

In the pathogenesis of chronic cholecystitis, a major role belongs to factors that change the condition of the gallbladder wall:

• the violation of blood supply in hypertensive disease, atherosclerosis of the vessels of the abdominal cavity, nodular periarteritis and other systemic vasculitis;
• long-term irritation of the gallbladder walls strongly thickened and physiologically-modified bile;
• Serous edema of the wall due to the influence of toxins, histamine-like substances formed in the inflammatory-infectious foci.

These factors reduce the resistance of the gallbladder wall, promote the introduction of infection and the development of the inflammatory process.

Allergic and immunoinflammatory reactions

The allergic factor and immuno-inflammatory reactions have a huge role in maintaining and progressing the inflammatory process in the gallbladder. As allergenic factors are bacterial and food allergens in the initial stages of the disease. Inclusion of the allergic component, the release of histamine and other mediators of an allergic reaction causes serous edema and non-infectious inflammation of the gallbladder wall. In the future, non-microbial ("aseptic") inflammation is maintained by autoimmune processes that develop as a result of repeated damage to the gallbladder wall. In the future, specific and nonspecific sensitization develops, a pathogenetic vicious circle is formed: inflammation in the gallbladder contributes to the ingestion of microbial antigens and antigenic substances in the wall of the bladder, in response to this, immune and autoimmune reactions develop in the wall of the bladder, which aggravates and supports inflammation.

Pathological examination of the gallbladder reveals the following changes in chronic cholecystitis:

• edema and varying degrees of severity of leukocyte infiltration of the mucous membrane and the remaining layers of the wall;
• thickening, sclerosis, wall compaction;
• with long-term chronic cholecystitis, the thickening and sclerosis of the gallbladder wall are sharply expressed, the blister is wrinkled, pericholecystitis develops, and its contractile function is significantly impaired.

Most often with chronic cholecystitis, catarrhal inflammation is observed, but with a pronounced inflammation, a phlegmonous and very rarely gangrenous process can be observed. Long-term inflammation can lead to a violation of the outflow of bile (especially in cervical cholecystitis) and the formation of "inflammatory congestion", which can cause even a dropsy of the gallbladder.

Chronic cholecystitis can lead to the development of secondary (reactive) chronic hepatitis (the old name is chronic cholecystoglue), cholangitis, pancreatitis, gastritis, duodenitis. Chronic galloping cholecystitis creates the prerequisites for the development of gallstones.

[1], [2], [3], [4], [5], [6]

Pathogenesis of chronic cholecystitis

At the basis of the development of chronic cholecystitis and dyskinesia of the bile ducts is a chronic violation of duodenal patency. Hypermotor dyskinesia develops with a compensated form of chronic disturbance of duodenal patency, this type of dyskinesia allows to overcome the obstacle for the outflow of bile in the form of high pressure in the duodenum with chronic violation of duodenal patency. Hypomotor dyskinesia develops with a decompensated form of chronic disturbance of duodenal patency.

In patients with chronic impairment of duodenal patency, there is a failure of the pyloric valve and the large duodenal nipple, which leads to the casting of duodenal contents into the biliary tract, infection of bile and the development of bacterial cholecystitis. During reflux of duodenal contents in the bile ducts enterokinase of intestinal juice activates trypsinogen, pancreatic juice with active trypsin is thrown into the bile duct, enzymatic cholecystitis develops.