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Gallbladder Pathology Online

Pathology of the Cholesterol Gallstones

Dr  Sampurna Roy  MD                                   


A cholesterol stone is usually solitary (the cholesterol 'solitaire').

It is oval or rounded in shape, and vary from 1 to 4 cm in diameter, or larger.

It is light in weight as well as in color.

In its absolutely pure state it is very pale yellow in colour and feebly translucent.


More often bile pigments are deposited within it.

On section it has a radiating crystalline interior.

Cholesterol stones, which make up some 6% of all gallstones, are believed to be formed primarily in aseptic static bile (in a "stasis" gallbladder). They tend to reside in Hartmannís pouch.

The stone is composed of 50 to 100% cholesterol, the rest consists of calcium salts and mucin.

Cholesterol stones are often detected at autopsy. During their reproductive period, women are three times more likely to develop cholesterol gallstones than men.

The incidence is higher in users of oral contraceptives and in women with several pregnancies.

Cholesterol gallstones are common in certain ethnic group. This may be due to the genetic factors.

Blacks in the US have a lower incidence of gallstones than whites, but a higher incidence than blacks in Africa. This difference probably reflects environmental influence, although a role of genetic admixtures is also possible.

It  has been suggested by some authors that gram-positive cocci are associated with the formation of pure cholesterol stones.

Mixed (secondary or inflammatory) gallstones may be formed later, or a mixed covering of pigment and cholesterol may form around the primary cholesterol stone. This is known as combination stone.


Pathogenesis of cholesterol stones relates mainly to the composition of the bile.

Normally, cholesterol, a compound highly insoluble in water, is secreted by the hepatocytes into the bile, where it is held in solution by the combined action of the bile acids and lecithin and carried in the form of mixed lipid micelles.

If the bile contains excess cholesterol or is deficient in bile acids, the bile becomes supersaturated, and under some circumstances the cholesterol precipitates as solid crystals.

The bile of persons with cholesterol gallstones has more cholesterol as it leaves the liver than that of normal individuals, pointing to the liver, rather than gallbladder as the culprit in the genesis of cholesterol stones.

The hepatocytes of patients with cholesterol gallstones are deficient in cholesterol 7 alpha-hydroxylase, the enzyme involved in the rate-limiting step by which bile salts are formed from cholesterol. 

As a result, the total size of the bile salt pool is reduced.

The resulting decrease in bile salt secretion contributes to the stone-forming (lithogenic) properties of the bile.

In obese patients, cholesterol secretion by the liver is increased,  adding to the supersaturation of the bile with cholesterol.

Although cholesterol supersaturation of the bile is   required for gallstone formation , additional factors are also required.

Cholesterol does not precipitate from saturated bile obtained from patients without gallstones.

Bile from patients without gallstones, but with properties similar to those in the bile of patients with gallstones, crystallizes without difficulty.

It is thought that the mucinous glycoproteins secreted by the gallbladder epithelium provide the necessary nidus for crystallization.

Risk factors:

The higher prevalence of gallstones in premenopausal women has been attributed to the fact that estrogens stimulate the formation of lithogenic bile by the liver.

Estrogens increase the hepatic secretion of cholesterol and may decrease the secretion of bile acids.

These effects are augmented during pregnancy, because the gallbladder empties more slowly in the last trimester, thereby causing stasis and increasing the opportunity for precipitation of cholesterol crystals.

Progesterone has been shows to inhibit discharge of bile from the gallbladder.

These mechanisms are also invoked to explain the increased incidence of gallstones in users of oral contraceptives.

Other risk factors for the development of cholesterol gallstones can be divided into those that relate to increased biliary cholesterol secretion, those that relate to decreased secretion of bile salts and lecithin, and those that relate to combination of the two.

Risk factors associated with increased biliary cholesterol secretion include the following:

- Age ;

- Food - i) high calory diet  and

           ii) High intake of Cholesterol

- Obese patients ;

- Certain ethnic groups  

- Familial  predisposition ;  

- Metabolic abnormalities- Example: Diabetes ; Genetic hyperlipoproteinemias, Primary biliary cirrhosis.

Decreased secretion of bile salts and lecithin may occur in nonobese patients who develop gallstones.

Gastrointestinal absorptive disorders that interfere with the enterohepatic circulation of bile acids, for instance pancreatic insufficiency secondary to cystic fibrosis and Crohn's disease also decrease secretion of bile acids and favour gallstone formation.

Visit: Pigment stones (calcium bilirubinate) ; "Mixed" stones


Further reading:

Role of diet in cholesterol gallstone formation.

Diet as a risk factor for cholesterol gallstone disease

Formation of cholesterol gallstones: the role of metabolic factors and of congestion

Disorders of bile acid metabolism in cholesterol gallstone

Effect of hypolipidemic treatment on the composition of bile and the risk of cholesterol gallstone disease  

Solitary versus multiple cholesterol gallbladder stones

Gram-positive cocci are associated with the formation of completely pure cholesterol stone

Cholesterol gallstone pathogenesis: a study of potential nucleating agents for cholesterol crystal formation in bile

Evidence for a potent nucleating factor in the gallbladder

Genetic predisposition of cholesterol gallstone disease.

ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease.

Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China.

Effect of the type of dietary fat on biliary lipid composition and bile lithogenicity in humans with cholesterol gallstone disease

Helicobacter pylori in the etiology of cholesterol gallstones

Evidence for a potent nucleating factor in the gallbladder bile of patients with cholesterol gallstones. 

Cholesterol gallstones and cancer of gallbladder (CAGB): molecular links.

Characterization of a small vesicular cholesterol carrier in human gallbladder bile











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