Chronic cholecystitis - Pathogenesis

Microflora in the gallbladder is detected 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 (only typhoid bacillus can normally develop in bile), as well as the bactericidal ability of the liver (with normally functioning liver tissue, microbes that enter the liver by hematogenous or lymphogenous routes die). The presence of bacteria in the gallbladder is not yet 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, this is what indicates the undoubted role of infection in the development of chronic cholecystitis.

Therefore, the penetration of infection into the gallbladder alone is not enough for the development of chronic cholecystitis. Microbial inflammation of the gallbladder develops only when infection of bile occurs against the background of bile stagnation, changes in its properties (dyskholia), damage to the gallbladder wall, and a decrease in the protective properties of the immune system.

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

• Neurodystrophic changes in the gallbladder wall

The development of neurodystrophic changes in the gallbladder wall is facilitated by biliary dyskinesia, which accompanies almost every case of chronic cholecystitis. According to some researchers, morphological changes in the wall of the gallbladder appear already with gallbladder dyskinesia: first, in the receptor apparatus of nerve cells and the neurons themselves, then in the mucous membrane and muscle layer of the gallbladder, i.e., 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, they 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 dysfunctions of the autonomic nervous system and endocrine system, including the gastrointestinal system. These disorders, on the one hand, cause the development of biliary dyskinesia, on the other hand, contribute to bile stasis and dystrophic changes in the gallbladder wall.

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

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

With dysfunction of the autonomic nervous system, the principle of synergism is violated, dyskinesia of the gallbladder develops, and the outflow of bile is impeded. Hyperactivity of the sympathetic nervous system contributes to the development of hypotonic, and hypertonicity of the vagus nerve - hypertonic dyskinesia of the gallbladder.

Contraction and emptying of the gallbladder is also carried out with the assistance of the phrenic nerve.

• Stagnation and dyscholia of bile

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

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

• Violation of the gallbladder wall condition

In the pathogenesis of chronic cholecystitis, a major role is played by factors that change the condition of the gallbladder wall:

• circulatory disorders in hypertension, atherosclerosis of the abdominal vessels, periarteritis nodosa and other systemic vasculitis;
• prolonged irritation of the gallbladder walls by highly thickened and physically and chemically altered bile;
• serous edema of the wall due to the influence of toxins, histamine-like substances formed in inflammatory and infectious foci.

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

Allergic and immunoinflammatory reactions

Allergic factors and immune-inflammatory reactions play a huge role in maintaining and progressing the inflammatory process in the gallbladder. Bacterial and food allergens act as allergenic factors in the initial stages of the disease. The inclusion of an allergic component, the release of histamine and other mediators of the allergic reaction cause serous edema and non-infectious inflammation of the gallbladder wall. Subsequently, non-microbial ("aseptic") inflammation is maintained by autoimmune processes that develop as a result of repeated damage to the gallbladder wall. Subsequently, specific and non-specific sensitization develop, a pathogenetic vicious circle is formed: inflammation in the gallbladder promotes the entry of microbial antigens and antigenic substances of the gallbladder wall into the blood, in response to this, immune and autoimmune reactions develop in the bladder wall, which aggravates and maintains inflammation.

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

• swelling and varying degrees of leukocyte infiltration of the mucous membrane and other layers of the wall;
• thickening, sclerosis, compaction of the wall;
• In long-term chronic cholecystitis, thickening and sclerosis of the gallbladder wall are sharply expressed, the bladder shrinks, pericholecystitis develops, and its contractile function is significantly impaired.

Most often, chronic cholecystitis is characterized by catarrhal inflammation, however, with severe inflammation, a phlegmonous and very rarely gangrenous process may be observed. Long-term inflammation can lead to a disruption of bile outflow (especially with cervical cholecystitis) and the formation of "inflammatory plugs" that can even cause dropsy of the gallbladder.

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

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Pathogenesis of chronic cholecystitis

Chronic cholecystitis and biliary dyskinesia are based on chronic duodenal obstruction. Hypermotor dyskinesia develops with a compensated form of chronic duodenal obstruction; this type of dyskinesia allows one to overcome the obstacle to bile outflow in the form of high pressure in the duodenum with chronic duodenal obstruction. Hypomotor dyskinesia develops with a decompensated form of chronic duodenal obstruction.

Patients with chronic duodenal obstruction have insufficiency of the pyloric valve and large duodenal papilla, which leads to the reflux of duodenal contents into the bile ducts, infection of the bile and the development of bacterial cholecystitis. During the reflux of duodenal contents into the bile ducts, enterokinase of intestinal juice activates trypsinogen, pancreatic juice with active trypsin is thrown into the bile duct, and enzymatic cholecystitis develops.