Cholelithiasis: causes, symptoms, diagnosis, treatment

Cholelithiasis refers to the presence of one or more stones (gallstones) in the gallbladder.

In the United States, 20% of people over age 65 have gallstones, and most extrahepatic biliary tract disorders result from cholelithiasis. Gallstones may be asymptomatic or cause biliary colic but not dyspepsia. Other major complications of cholelithiasis include cholecystitis; biliary tract obstruction (stones in the bile duct), sometimes with infection (cholangitis); and biliary pancreatitis. Diagnosis is usually made by ultrasound. If cholelithiasis causes complications, cholecystectomy may be necessary.

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What causes cholelithiasis?

Risk factors for gallstones include female gender, obesity, age, ethnicity (American Indian in the United States), Western diet, and family history.

Gallstones and bile sludge are formed from different types of substances.

Cholesterol stones account for more than 85% of gallstones in Western countries. Three conditions are necessary for the formation of cholesterol gallstones.

1. Bile is supersaturated with cholesterol. Normally, water-insoluble cholesterol becomes water-soluble when combined with bile salts and lecithin. Mixed micelles are formed. Hypersaturation of bile with cholesterol may result from increased secretion of cholesterol (e.g., in diabetes), decreased secretion of bile salts (e.g., in fat malabsorption), or lecithin deficiency (e.g., in genetic disorders causing a form of progressive intrahepatic hereditary cholestasis).
2. Excess cholesterol precipitates from solution as solid microcrystals. Precipitation is accelerated by mucin, fibronectin, su globulin, or immunoglobulin. Apolipoproteins A-I and A-II may slow the process.
3. Microcrystals form complexes. The aggregation process is facilitated by mucin, decreased contractility of the gallbladder (which is a direct result of excess cholesterol in the bile) and slower passage of contents through the intestine, which facilitates bacterial transformation of cholic acid into deoxycholic acid.

Bile sediment consists of bilirubinate calcium, cholesterol microcrystals, and mucin. Sludge is formed by stagnation in the gallbladder, which occurs during pregnancy or total parenteral nutrition (TPN). Sludge is usually asymptomatic and disappears if the first condition for stone formation is eliminated. On the other hand, sludge can lead to biliary colic, gallstone formation, or pancreatitis.

Black pigment stones are small and hard, composed of calcium bilirubinate and inorganic calcium salts (eg, calcium carbonate, calcium phosphate). Factors that accelerate stone formation include alcoholism, chronic hemolysis, and old age.

Brown pigment stones are soft and greasy, composed of bilirubinate and fatty acids (calcium palmitate or stearate). They form as a result of infection, parasitic infestation (eg, liver fluke in Asia), and inflammation.

Gallstones enlarge at a rate of approximately 1–2 mm per year, reaching a size that can cause specific problems within 5–20 years. Most gallstones form in the gallbladder, but brown pigment stones may form in the ducts. Gallstones may migrate into the bile duct after cholecystectomy or, especially in the case of brown pigment stones, form over a stricture as a result of stasis.

Symptoms of cholelithiasis

Gallstones are asymptomatic in 80% of cases; in the remaining 20%, symptoms range from biliary colic and signs of cholecystitis to severe and life-threatening cholangitis. Patients with diabetes are predisposed to particularly severe manifestations of the disease. Stones can migrate into the cystic duct without clinical manifestations. However, when the cystic duct is blocked, pain (biliary colic) usually occurs. The pain occurs in the right hypochondrium, but can often be localized or manifest in other parts of the abdomen, especially in patients with diabetes and the elderly. The pain can radiate to the back or arm. It begins suddenly, becoming increasingly intense over 15 minutes to 1 hour, remaining constant for the next 1-6 hours, then gradually disappearing after 30-90 minutes, acquiring the character of a dull ache. The pain is usually severe. Nausea and vomiting are common, but neither fever nor chills occur. Palpation reveals moderate pain in the right hypochondrium and epigastrium, but peritoneal symptoms are not elicited, and laboratory values are within normal limits. Between episodes of pain, the patient feels satisfactory.

Although biliary colic-type pain may occur after eating heavy meals, fatty foods are not a specific trigger. Dyspepsia symptoms such as belching, bloating, vomiting, and nausea are not exactly associated with gallbladder disease. These symptoms may be seen in cholelithiasis, peptic ulcer disease, and functional gastrointestinal disorders.

The severity and frequency of biliary colic weakly correlate with pathological changes in the gallbladder. Biliary colic can develop even in the absence of cholecystitis. However, if the colic lasts more than 6 hours, vomiting or fever is present, there is a high probability of developing acute cholecystitis or pancreatitis.

Diagnosis of cholelithiasis

Gallstones are suspected in patients with biliary colic. Laboratory tests are usually uninformative. Abdominal ultrasound is the main diagnostic method for cholecystolithiasis, with a sensitivity and specificity of 95%. Biliary sludge may also be detected. CT and MRI, as well as oral cholecystography (rarely used today, but quite informative) are alternatives. Endoscopic ultrasound is particularly informative in diagnosing gallstones smaller than 3 mm when other methods give ambiguous results. Asymptomatic gallstones are often detected incidentally during examinations performed for other indications (e.g., 10-15% of calcified non-cholesterol stones are visualized on plain radiographs).

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Treatment of cholelithiasis

Asymptomatic Gallstones

Clinical manifestations of asymptomatic gallstones occur in an average of 2% of patients per year. Most patients with asymptomatic cholecystolithiasis do not consider it worth the inconvenience, expense, and risk of surgical intervention to remove an organ whose disease may never manifest clinically, despite all the possible complications. However, in patients with diabetes, asymptomatic gallstones should be removed.

Gallstones with clinical symptoms

Although biliary colic occurs spontaneously in most cases, signs of biliary pathology recur in 20-40% of patients per year, and complications such as cholecystitis, choledocholithiasis, cholangitis and pancreatitis develop in 1-2% of patients annually. So there are all indications for gallbladder removal (cholecystectomy).

Open cholecystectomy, which involves laparotomy, is a safe and effective procedure. If it is performed routinely before complications develop, the overall mortality rate does not exceed 0.1-0.5%. However, laparoscopic cholecystectomy has become the method of choice. This type of surgery results in faster recovery, with little postoperative discomfort, better cosmetic results, and no worsening of postoperative complications or mortality. In 5% of cases, due to difficulties in full anatomical visualization of the gallbladder or the possibility of complications with laparoscopic cholecystectomy, open surgery is used. Old age generally increases the risk of any type of intervention.

In patients with biliary colic, episodes of pain usually disappear after cholecystectomy. For unexplained reasons, a number of patients with dyspepsia and fatty intolerance before surgery have had these symptoms disappear after surgery. Cholecystectomy does not cause nutritional problems, and no dietary restrictions are required after surgery. Some patients develop diarrhea, often due to malabsorption of bile salts.

In patients for whom surgery is contraindicated or for whom the risk of surgery is high (eg, due to comorbidity or advanced age), dissolution of gallstones with oral bile acids for several months may sometimes be used. The stones should be cholesterol (radiolucent on plain abdominal X-ray) and the gallbladder should not be obstructed, as confirmed by cholescintigraphy or, if possible, oral cholecystography. However, some clinicians believe that stones in the neck of the cystic duct do not cause cystic duct obstruction and therefore do not recommend cholescintigraphy or oral cholecystography. Ursodiol (ursodeoxycholic acid) 8-10 mg/kg/day orally in 2-3 divided doses is used; the main dose is taken in the evening (eg, 2/3 or 3/4) reduces secretion and saturation of bile with cholesterol. Because of the high surface area to volume ratio, small gallstones dissolve faster (eg, 80% of stones <0.5 cm dissolve within 6 months). With larger stones, the efficacy is lower, even with higher doses of ursodeoxycholic acid (10-12 mg/kg/day). In approximately 15-20% of patients, stones <1 cm dissolve in 40% of cases after 2 years of treatment. However, even after complete dissolution, stones recur in 50% of patients within 5 years. Ursodeoxycholic acid can prevent stone formation in obese patients who are rapidly losing weight as a result of gastric bypass surgery or after a low-calorie diet. Alternative methods of stone dissolution (injection of methyl tributyl ether directly into the gallbladder) or their fragmentation (extracorporeal wave lithotripsy) are currently practically not used, since laparoscopic cholecystectomy is the treatment of choice.