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The gallbladder dysfunction is a disorder of the gallbladder contraction which reveals as biliary pain (1). The cause of the gallbladder hypomotility can be an increased basal cystic duct resistance or cystic duct spasm, the muscle hypertrophy, or the chronic gallbladder diseases.
Diagnostic criteria of the gallbladder dysfunction
- Recurrent episodes of moderate or severe pain in the right hypochondrium or epigastrium which last for 20 minutes and more (pain is defined as moderate when it disrupts the patient’s daily activities, and as severe when medical consultation or medication is necessary).
- In addition, a patient may also experience one or more of the following symptoms:
- Nausea and vomiting
- Irradiation of pain in the right scapular region or in the right shoulder
- Pain occurs after a meal
- Pain occurs at night
- Impaired gallbladder emptying (the gallbladder ejection fraction is less than 40%).
- Absence of structural (morphological) changes explaining these symptoms.
Causes of the gallbladder evacuation dysfunction
- Pathology of the smooth muscle cells and epithelial cells in the gallbladder wall (high degree of COX-2 expression in the smooth muscle cells and epithelial cells of the gallbladder wall).
- Contractile dyscoordination of the gallbladder and cystic duct (high degree of COX-2 expression in the smooth muscle cells of the gallbladder and cystic duct).
- The cystic duct resistance increase (high degree of COX-2 expression in the smooth muscle cells of the cystic duct).
Mechanism of development of pathologic disorders
Decrease in the evacuation function of the gallbladder to less than 40% results in the decrease in the “active” and “passive” passage of the hepatic bile into the gallbladder and in the concentration of total bile acids in the gallbladder bile (fig. 11).
The decrease of the “active” and “passive” passage of the hepatic bile into the gallbladder results in the increase of the passage of the hepatic bile into duodenum and of the gallbladder-independent enterohepatic circulation of bile acids, biliary cholesterol and biliary bilirubin (fig. 12).
The increase of the gallbladder-independent enterohepatic circulation of bile acids causes increase in the concentration of bile acids in the hepatocytes and in the decrease of excretion function of the liver (i.e. formation of chronic “bland” intrahepatic cholestasis) (fig. 12).
The increase of the gallbladder-independent enterohepatic circulation of biliary cholesterol causes increase in the absorption of the biliary cholesterol in the small intestine, the biliary cholesterol entering the hepatocytes and the high secretion into hepatic bile (fig. 13). These two factors cause the formation of the “lithogenic” hepatic bile.
Decrease of the gallbladder-dependent output of biliary cholesterol and of the concentration of total bile acids in the gallbladder bile cause formation of the “lithogenic” gallbladder bile and precipitation of cholesterol monohydrate crystals in the gallbladder lumen on 10% of the patients with gallbladder dysfunction (fig. 14).
Precipitation of cholesterol monohydrate crystals on the epithelial cells of the gallbladder causes increase in COX-2 activity in the epithelial cells of the gallbladder mucosa and transformation of the gallbladder dysfunction into chronic acalculous cholecystitis without biliary sludge.
Pathogenetic treatment of patients with gallbladder dysfunction
Treatment of gallbladder dysfunction (gallbladder hypomotility with biliary pain) and for prophylactics of the chronic acalculous cholecystitis includes:
- Celecoxib - 100 mg, 2 times a day after meal for 5-7 days, after which
- Ursodeoxycholic acid - 750 mg, once a day (in the evening) for 2 weeks.
Celecoxib is a selective inhibitor of COX-2. Inhibiting COX-2 activity in the smooth muscle cells of the gallbladder wall and cystic duct results in the relief of the biliary pain within 3-5 days, restoration of the evacuation function of the gallbladder and the gallbladder-dependent output of biliary cholesterol, “active” passage of the hepatic bile into the gallbladder, and decrease in the gallbladder-independent enterohepatic circulation of bile acids, biliary cholesterol and biliary bilirubin.
Ursodeoxycholic acid, is a hydrophilic hepatoprotective bile acid. It helps in dissolving the cholesterol monohydrate crystals in the gallbladder, decrease in lithogenicity of the gallbladder and hepatic bile, disappearance of the chronic “bland” intrahepatic cholestasis (i.e. results in the restoration of the excretion function of the liver).
Effectiveness is 95%.
Remission period is 18-24 months.
Attention!!! Information for patients:
Before using this scheme of treatment please check the contraindications (below) and side effects of using pharmacological preparations of Celecoxib and Ursodeoxycholic acid, and obtain your doctor’s permission.
Contraindications for Celecoxib:
- allergic reactions (nettle-rash, bronchial spasm) to acetylsalicylic acid or other NSAIDs (in anamnesis);
- 3rd trimester of pregnancy;
- high sensitivity to sulphonamides;
- high sensitivity to any component of the preparation.
Contraindications for Ursodeoxycholic acid:
- high sensitivity to the preparation;
- acute inflammatory diseases of the gallbladder and the bile ducts;
- ulcerative colitis;
- Crone’s disease.
This web page does not bear any legal responsibility for the use of the proposed treatment schemes without consulting your doctor.
- Extrahepatic biliary system diseases: the gallbladder dysfunction and states after cholecystectomy. International Bulletin: gastroenterology. 2001; 6: 1-4.
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