Bile

(Date of publication 05 March 2004)

Bile has had a very bad press over the years. According to the humoral theory of medicine developed by the Ancient Greeks, the body consisted of four fluids (or humours), each of which gave off a specific vapour that ascended to the brain and defined the personality. Of the humours, yellow bile was associated with irritability and bad temper, while black bile was linked to depression. This theory persisted until the 17th century and the primary form of medical treatment was bloodletting to remove 'bad' humour, a complicated process in which the phlebotomy site was critically important. However, irascibility and melancholy are not the whole story. We now have considerable scientific knowledge of the function of bile, and the humble sea lamprey appears to have a very positive view of one of its constituents, as we shall find out..

The lecture notes on bile are probably a good place to start. The liver secretes some 700 ml per day, which is then stored and concentrated in the gall bladder. It has an excretory component and also a secretory component, whose detergent action in the small intestine facilitates the digestion of fats. Secretion is regulated by both neural and hormonal mechanisms.

One constituent is cholesterol, basic information about which is available at the bottom of this page, including its chemical and structural formulae, molecular weight and dietary sources. The primary function of cholesterol is as a component of cell membranes, but it is also used for synthesising sex and stress hormones, and by the liver to manufacture bile acids. (If your interest is in the transport of cholesterol around the body and the distinction between high density lipoproteins ('good' cholesterol) and low density lipoproteins ('bad' cholesterol), there is a clear account here). Additional material about the various functions of cholesterol can be found on the degussa site, with plenty of links to more detailed information.

Bile acids play a vital role in the digestion and absorption of fats. They are manufactured in the liver and then conjugated with the amino acids glycine or taurine. Possessing both hydrophobic and hydrophilic properties they can emulsify lipid aggregates – increasing the surface area for attack by lipases – and solubilise many lipids by forming micelles. The synthesis of bile acids is the main mechanism for breaking down cholesterol in the body. Although some 500 mg are eliminated in this way each day, 95% of bile acids are re-absorbed by the blood to maintain cholesterol homeostasis. This means that each hard-working bile salt molecule is re-used about 20 times – see the natty animation about half-way down the page.

Lecithin in bile is also involved in eliminating cholesterol; for example, lecithin vesicles which transport cholesterol increase its solubility in bile nearly one million-fold. This site deals primarily with the formation of cholesterol gallstones from bile (in considerable detail). There is a photograph of two rather spendid examples (poor patient!) here. Essentially, macroscopic crystals form as lecithin-cholesterol vesicles revert to equilibrium via a process of aggregation and fusion. Wider coverage of gallstone formation points out that pigmented and mixed gallstones also occur, and that contributory factors include supersaturation of bile, nucleation factors, bile stasis and the amount of calcium present. The three different types of stone can be seen in this photograph.

Another constituent of bile is bilirubin, which results from the breakdown of haemoglobin in red blood cells, in the conjugated form of water-soluble diglucuronide. In the colon, oxidation and reduction by bacteria yield a variety of products, some of which are pigmented and give the stool its colour. In health, the plasma concentration of bilirubin is 0 - 20 mol/L. An increase to 50 mol/L will produce jaundice - see the photographs of the skin and sclera of affected patients here and here. Possible causes include increased bilirubin production (as in haemolytic anaemia), obstruction of the bile duct, and liver disease or damage. An important part of diagnosis is establishing whether the excess of bilirubin is in the unconjugated form bound to albumin, or in the form of diglucuronide. Some rare conditions produce congenital hyperbilirubinaemia and in neonates the distinction between the two types is critical, because unconjugated bilirubin is neurotoxic and can lead to permanent brain damage.

There are many other biliary conditions which result from abnormalities in bile composition, biliary anatomy and function. Important examples include gall bladder cancer, cholecystitis (inflammation of the gall bladder) and primary biliary cirrhosis, which accounts for between 0.6% and 2% of cirrhosis deaths world-wide. The great diversity of symptoms and the daunting task of differential diagnosis are comprehensively tackled on the emedicine site, which also has some good radiographs – look out for those illustrating the removal of stones from the common bile duct using a balloon-tipped catheter.

Now then, what about the sea lampreys? These creatures parasitise other fish and have invaded the Great Lakes in North America, with devastating effects on the fishing industry. Weiming Li of Michigan State University was looking at spawning to develop new lamprey controls and discovered that males release a pheromone which can attract the attention of females at least 65 metres downstream. Analysis revealed that this pheromone is a bile acid, and it must have evolved specifically for this purpose because adult lampreys do not eat and therefore have no need for digestion!

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A Tour around Bile

A Tour around Bile