Stones in the gallbladder

Prevalence

Gallstones are very common, with a prevalence at autopsy of 11 to 36 per cent. There are at least 5 million people in the United Kingdom and 25 million people in the United States of America with gallstones. Overall the prevalence has probably increased in Western societies over the last 50 years, and it certainly increases with age, from 4 per cent of people in the third decade to 27 per cent in the seventh. This may be related to changes in the biochemistry of bile with age. Women are three times more likely than men to develop stones, and first-degree relatives of patients with gallstones have a two-fold greater prevalence. There are geographical variations. The prevalence is very high in certain American Indian communities (Pima and Chippewa tribes), in Mexico, Sweden, Czechoslovakia, and Chile, and low in Greece, Japan, India, and China. Certain conditions predispose to the development of gallstones. Obesity is a risk factor for gallstones in women under the age of 50. Pregnancy, but not consumption of the oral contraceptive pill, probably predisposes to the development of gallstones (Fig. 20) 1243. Dietary factors which have been implicated include a high energy intake, increased consumption of unrefined carbohydrate, and diets low in fibre. Crohn's disease, terminal ileal resection, and jejunoileal bypass for obesity are associated with a four-fold increase in prevalence. Biliary infection and parasitic infestation of the biliary tree are important factors in the development of pigment stones in Asia but not in the West. Other diseases associated with the development of gallstones include diabetes mellitus, type IV hyperlipoproteinaemia, cirrhosis of the liver, gastric surgery, and total parenteral nutrition. Patients with haemolytic anaemia due to hereditary spherocytosis, sickle-cell disease, and thalassaemia also show an increased prevalence of pigment stones.

 

Classification of stones

Cholesterol and bile pigments are the two principal constituents of gallstones. In addition, calcium carbonate, phosphate, and palmitate are present in variable amounts. Pure cholesterol and pure pigment stones do occur, but most stones are mixed (Fig. 21) 1244. Predominantly cholesterol stones account for 75 per cent of all gallstones in the West. They are single or multiple, hard, and usually layered on cross-section (Fig. 22) 1245. Pigment stones are most common in Asia. They are usually black or brown in colour; brown stones crumble when squashed (Fig. 23) 1246. About 10 per cent of stones contain enough calcium to be radio-opaque (Fig. 7) 1230.

 

Formation of gallstones

Cholesterol stones

Cholesterol is insoluble in water, and is held in solution as micelles of cholesterol, phospholipids, and bile salts. Lecithin forms the major component of phospholipids while the bile salts are glycine or taurine conjugates. The physicochemical state of bile can be determined from a phase diagram (Fig. 24) 1247. The relative proportions of cholesterol, bile salts, and phospholipid are expressed as a percentage of the total lipid content and are plotted on triangular co-ordinates. An increase in the cholesterol concentration or a decrease in the bile salt concentration results in supersaturation of bile with cholesterol, and the formation of a liquid crystalline phase of cholesterol.

 

The biliary lipid composition of normal bile and gallstone bile is virtually identical, and since at least half of the Western population have supersaturated bile there must be another factor responsible for the formation of stones. Cholesterol will only crystallize from a supersaturated solution if there is a nidus on which the crystals can form. This process is called nucleation, and the time taken for supersaturated bile to form crystals of cholesterol is known as the nucleation time. Normal bile takes 15 days to form crystals, compared with 3 days for bile from patients with cholesterol gallstones. Mucus glycoproteins from the gallbladder wall and bilirubinate have both been proposed as nucleating factors, while a bile protein has been proposed as an inhibitor. The nucleation phenomenon also depends on gallbladder function: the motility of the wall determines the degree of stasis and mixing of the bile within the lumen. One other significant finding is that the size of the bile acid pool is reduced in many patients with gallstones, although the reason for this is unknown.

 

Pigment stones

Pigment gallstones are formed of calcium bilirubinate and contain less than 25 per cent cholesterol (Fig. 23) 1246. They are usually small and multiple, and about half are radio-opaque. As might be expected they are more prevalent in patients with haemolytic disorders such as hereditary spherocytosis or sickle-cell disease, and in patients with cirrhosis, who commonly have a mild degree of haemolysis. They are frequently found in oriental countries, where they are associated with parasitic infections. Bilirubin in bile is normally conjugated with glucuronide. The enzyme & bgr; -glucuronidase, which may be produced by bacteria such as Escherichia coli, splits the molecule and the unconjugated bilirubin precipitates as the calcium salt. Hydrolytic enzymes from gallbladder mucosa may act in the same way.

 

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