Gallstones

Chapter 49 Gallstones

What are the complications of gallstone disease?

The condition of having gallstones is called cholelithiasis. It is common, particularly in industrialized countries, where postmortem studies have found an overall prevalence in adults of approximately 10–20% in the elderly. Females are affected two or three times more often as males. Gallstones are often asymptomatic but can cause inflammation or obstruction.

Stones (calculi) can form in other bodily fluids too (e.g. urine and saliva, causing urolithiasis and sialolithiasis, respectively). Some of the principles of stone formation described in this chapter, such as supersaturation and nucleation, apply to all of these sites.

Most gallstones consist of a mixture of bile pigments and cholesterol. Nevertheless, one of these constituents usually predominates, and so gallstones can be classified as being cholesterol stones or pigment stones. The significance of this classification stems from the different pathogenesis of the two types.

Pathogenesis

Cholesterol stones account for the majority of gallstones in industrialized countries, whereas they are uncommon in non-industrialized countries. The pathophysiology of their formation is summarized in Fig. 3.49.1. Cholesterol dissolves in bile through the detergent actions of lecithin and bile salts. If there is an excess of cholesterol, the solution becomes supersaturated and crystals of cholesterol monohydrate may precipitate if there is a nucleus on which they can begin to grow. Anything that acts as a substrate for crystal growth can act as a nucleus, for example a tiny crystal that forms spontaneously or a particle of mucus. The bile normally contains proteins that tend to inhibit nucleation (antinucleating proteins) and protect against the risk of crystal formation if the bile becomes supersaturated.

Fig. 3.49.1 Summary of the main pathways involved in the pathogenesis of cholesterol stones.

Two factors promote nucleation in a supersaturated solution. First, hypomotility of the gallbladder, with consequent biliary stasis, allows time for nucleation and crystal growth to occur. As high cholesterol concentration in bile inhibits gallbladder motility, the presence of a supersaturated solution will itself produce this effect. Second, the ratio of antinucleating proteins to pronucleating proteins falls (the mechanism of this process is unclear). Consequently, there is an increased tendency for small crystals to form and then grow into stones.

Morphologically, cholesterol stones are yellow and their crystalline structure is revealed on examination of a cut surface (Fig. 3.49.2). They tend to be hard and can grow to several centimetres in diameter. Pure cholesterol stones are unusual; most of them also contain some bilirubin and calcium salts. Cholesterol stones with a high proportion of other ingredients are sometimes called mixed stones. In approximately 10% of patients, they contain sufficient calcium to make them radio-opaque to X-rays. Whether calcified or not, gallstones are detectable by ultrasound.