There are two types of gallstones: cholesterol stones and pigment stones. If you didn’t know anything about gallstones, you’d guess (rightly so) that cholesterol stones are made up of cholesterol. And you’d also probably guess that you get cholesterol stones when there’s too much cholesterol around. But how, exactly? And pigment stones – what are those made of? Pigment?
Turns out there are very good explanations for all of these questions. Let’s take a look.
Cholesterol gallstones contain – not surprisingly – cholesterol. And they arise when there’s more cholesterol around than the gallbladder can handle. But what does this actually mean?
A tiny bit of basic science here. Under normal conditions, cholesterol is soluble in bile because it binds to bile salts (which are water-soluble) and lecithins (which are water-insoluble). These guys both act like detergents, and cholesterol is dispersed within the bile, and everything’s cool.
But what happens if there’s too much cholesterol around? If the concentration of cholesterol exceeds the solubilizing capacity of bile, then cholesterol will nucleate into solid cholesterol crystals, which can over time get big enough to form stones.
These stones are made of unconjugated bilirubin (mixed with calcium salts). They’re called pigment gallstones because they’re dark brown to black in color (compared to cholesterol stones, which are usually pale yellowish-greenish in color).
The two main conditions in which you see pigment stones are chronic hemolytic anemia and infection of the biliary tract. Why would these conditions lead to an accumulation of unconjugated bilirubin in the bile? In order to answer that, let’s quickly review bilirubin metabolism in the bile itself.
Normally, the liver conjugates bilirubin and dumps it into the bile. So the bile contains just conjugated bilirubin, then, right? Wrong! About 1% of the bilirubin in bile undergoes deconjugation while it’s still in the biliary tree (betcha didn’t know that!). Bile is then dumped into the gut, where bacterial-glucuronidases convert most of the remaining conjugated bilirubin into its unconjugated form.
Back to the causes of pigmented stones. If you have an infection in the biliary tree, and the infectious agent makes glucuronidase, then you’ll end up deconjugating more bilirubin than normal…and over time, that unconjugated bilirubin can accumulate and form stones.
The other main cause of pigmented stones is chronic hemolysis. If you’re busting open lots of red cells, all that heme gets transformed into bilirubin, which the liver conjugates and dumps into the bile. So the bile contains a lot more bilirubin than usual. Most of that bilirubin remains conjugated – but around 1% is turned into unconjugated bilirubin right there in the biliary tree. If you’re making a lot more bilirubin than normal, that 1% is significant – and over time, that excess of unconjugated bilirubin can be enough to lead to pigment stones.