Introduction
Gallstones and biliary disease can be a bit confusing, and there is a lot of overlap. Essentially, gallstones themselves are not problematic in the vast majority of cases, but can predispose the other problems with the biliary tree.
Gallstones
The gallbladder is the second most common ‘organ’ (behind the appendix) that needs surgery in the GI tract. Stones can be classified as to what is in them, and then also (for treatment purposes) where they are causing a physiological problem.
Categorisation
- Bile contains: bile pigments (from Hb breakdown products), cholesterol, and other lipids.
- Stones are generally classified as cholesterol stones or pigment stones; however, in reality they are usually mixed. In the developed world, cholesterol stones are more common, but in the developing world, pigment stones are more common.
- In Europe and the USA, 75% of gallstones are cholesterol stones.
- Pure cholesterol stones -
- Usually solitary and large
- RF’s – female sex, age, obesity
- Stones of about 70% or more of cholesterol are usually smaller and more numerous. The rest of the stone is made up of calcium compounds and protein.
- Mixed stones:
- Usually multiple and irregular shaped
- Pigment stones can also be divided into two categories – Brown and black. Brown stones are softer, and contain a mixture of pigment, cholesterol and calcium salts. Black stones are much harder and made of pure pigment.
Epidemiology
- More common in women.
- Cholesterol secretion is a massive factor in gallstone formation – particularly the amount of cholesterol secreted in relation to the concentration of bile salts. Women naturally secrete a higher proportion of cholesterol than men and thus they have a higher incidence of gallstones.
- Incidence increases with age
- At age 30 – 5% of women and 2% of men have / have had gallstones. Aged 55 – 20% / 10%, age 70, 30% / 20%.
- Racial differences: More common in Scandinavia, and Native North and South American Populations.
Aetiology
- Weight
- Family History
- Oestrogen
- Diet (high fat, low fibre)
‘Fair, fat, female, forty’ used to be a term used to describe the typical patient with gallstones – however statistical research has shown that the risk for these patients is actually the same as that in the general population (but a lot of doctors still use this mantra).
Pathology
Cholesterol stones
- You need three factors for the formation of cholesterol stones:
- High concentration of cholesterol in the gallbladder
- Gallbladder stasis
- Products that promote the crystallisation of cholesterol – some lipoproteins found in bile do this.
- Cholesterol stones form when the concentration of micelles is not great enough to hold all the cholesterol in the micelles. Formation of stones is increased during fasting – particularly extended fasting e.g. in IV nutrition - as this increases the concentration of cholesterol in the gallbladder relative to other solutes.
- Patients with cholesterol stones generally have a smaller bile pool, which circulates more often.
- Formation - Initially, cholesterol crystals will form in bile that is supersaturated with cholesterol. This results in the production of ‘sludge’. This process is:
- Inhibited by – caffeine, NSAID’s and bile salts
- Exacerbated by – Mucin, rapid weight loss, pregnancy, increased serum cholesterol – e.g. by a large amount of body fat, old age, being female, diabetes, high dietary fat – reduced bile production / circulation – e.g. in malabsorption (like Crohn’s) where so much bile is lost, it cannot be replaced quickly enough.
- Drugs
- Clofibrate – A fibrate drug, this lowers plasma cholesterol by increasing cholesterol secretion in bile.
- Contraceptive pill
- Sludge can then go on to form stones, or it can be reabsorbed. Only in about 15% of cases will sludge go on to form stones. It takes about 8 years for a stone to form from the beginning of the initial process. In symptomatic patients, a cholecystectomy is usually performed 12 years after the process of stone formation began.
Pigment stones
The process of pigment stone formation is completely independent of that cholesterol stones.
Pigments in bile are from
bilirubin breakdown. There are 3 main causes that can lead to pigment stones:
- An increase in bilirubin load, as a result of haemolytic anaemia.
- 40-60% of patients with haemolytic disease have pigment stones, but the vast majority of pigment stones patients do not have haemolytic disease.
- Pigments become less water soluble once in the bile as a result of the action of glucuronidases. It is thought that most cases of pigment stones result from the subclinical bacterial colonisation of the gallbladder. This is particularly common in East Asia, and associated with E. coli. These stones tend to be softer and brown, and combined with calcium carbonate. The other two types of stone tend to be smaller, blacker and harder, and more commonly encountered in the west.
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