Gallstones (cholelithiasis) – causes, symptoms, diagnosis, treatment & pathology

Gallstones (cholelithiasis) – causes, symptoms, diagnosis, treatment & pathology


When you eat some real fatty foods, like say
some delicious french fries, they make their way to through the stomach and into the small
intestine. At this point they aren’t really french
fries anymore, but since they’re high in fat, they’re still a little more difficult
to absorb, and that’s where your gallbladder comes in. This high fat food stimulates the gallbladder
to squeeze out some bile into the small intestine, that bile emulsifies the fat, or basically
mixes the fat up, and makes it easier to absorb. This is pretty much your gallbladder’s job—store
and concentrate bile until the time comes to send it to the small intestine. It’s not the most glamorous of jobs, but
hey, gotta start somewhere. If we take a closer look at this magical substance,
we’d get a rough breakdown that’s something like the following: ~70% bile salts and acids,
~10% cholesterol ~5% phospholipids, ~5% proteins,, and 1% conjugated bilirubin, and the rest,
small amounts of various other compounds like water, electrolytes, and bicarbonate. Bile salts and acids are mostly a product
of cholesterol metabolism, so an acid might look something like this and its salt is the
anionic form, something like this (ROO-) group. These acids and their salts have both hydrophobic
and hydrophilic sides, making them amphiphilic, which help them make cholesterol and fat in
the gut more soluble in bile. The phospholipids are mostly lecithin, also
amphiphilic, and also help make cholesterol and fats more soluble in bile. Gall-stones are these round and solid stones
you can find inside your gallbladder, and they’re made from the components of bile,
and so they’re categorized depending on what they’re made of, the most common ones
are cholesterol stones, but there’s also bilirubin stones, which are sometimes called
pigmented stones. The first type, as you might guess, are made
mostly of cholesterol that has precipitated out of the bile as a solid and formed these
solid stones. These account for around 75 to 90% of cases. This cholesterol precipitation can happen
in a couple ways, first, the bile can become supersaturated with cholesterol, meaning that
the bile has so much cholesterol that the bile salts and acids or phospholipids can’t
hold any more in solution, because remember that these all help make the cholesterol more
soluble in bile, and so the cholesterol comes out of solution as a solid. Another, somewhat similar way, is if you don’t
have enough of these bile salts or acids and phospholipids to help keep the cholesterol
in solution, so the less you have, the less cholesterol can be in solution and the more
precipitates out. Gallbladder stasis, or inactivity, has also
been linked to forming stones, if the bile just sits there it can cause the solid to
separate and precipitate out, kind of like when the oil in your peanut butter jar separates
from the peanuts if it just sits too long. Stones that’re made of cholesterol can’t
be seen on x-ray, but rarely are the stones only cholesterol, and usually you’ll see
a bit of a mixed composition; if they have enough calcium carbonate they might be able
to be seen on x-ray. Remember that we said there’s a small amount
of electrolytes and bicarbonate? Well some of those electrolytes are calcium
ions, and calcium ions tend to form insoluble precipitates with bicarbonate as calcium carbonate,
which would be radio-opaque, and visible on x-ray, but usually there’s not enough calcium
carbonate and the cholesterol stones will be radiolucent on x-ray and you won’t be
able to see them. Alright, so the other type is bilirubin or
pigmented gallstones. These ones, again, are pretty self-explanatory
and are made mostly of bilirubin and therefore are pigmented. These are made when there’s too much bilirubin
in the bile and it has combined with calcium to form the solid precipitate calcium bilirubinate. Since they’re made partly of calcium, they’ll
usually be radiopaque, meaning you can see them on x-ray, here’s an example showing
pigmented gallstones on x-ray. Since it’s the bilirubin in bile, we’d
maybe assume that they’re made of conjugated bilirubin, right? Well, actually pigmented gallstones are made
of unconjugated bilirubin. What? I thought there was only conjugated bilirubin
in bile? Well the vast majority is conjugated, but
there is a small amount of unconjugated bilirubin in bile, only about 1-2% of total bilirubin,
which is only 1% of bile. Although the exact mechanism is unclear, this
tiny tiny amount of unconjugated bilirubin is thought to form from nonbacterial and nonenzymatic
hydrolysis of conjugated bilirubin, so through a reaction in the chemical environment of
bile that doesn’t involve enzymes or bacteria. K quick breakdown of the structure of conjugated
vs. unconjugated bilirubin: the conjugated form has this R-group, glucuronic acid, that
makes it water soluble, unconjugated just has this OH group, which at the pH of bile,
is in anionic form that’d probably really like to bind with calcium. Usually though, bile salts bind up the calcium
ions and keep them from binding with and precipitating unconjugated bilirubin. With extravascular hemolysis, we have macrophages
eating up red blood cells more than normal and unconjugated bilirubin production is ramped
up, which is conjugated by the liver and sent to the gallbladder. These situations where there’s a lot of
hemolysis and unconjugated bilirubin production, there’s going to eventually be more conjugated
bilirubin produced, and it’s thought that when there’s more conjugated bilirubin in
the bile, there’s also more unconjugated bilirubin, to the point where it can now bind
calcium instead of the bile salts, and precipitate out to form black pigmented stones. If the gallstone is brown pigmented, it’s
often a sign of gallbladder or biliary tract infection, and often the stones have even
ventured outside gallbladder and into the bile ducts. These brown gallstones are also made of the
calcium salts of unconjugated bilirubin, what’s different, though, is how the unconjugated
bilirubin forms: what happens is that a bacteria that causes gallbladder infection, like E
coli., for example, brings about hydrolytic enzymes that hydrolyze both conjugated bilirubin
and phospholipids, that again combine with calcium ions, which then precipitates out
to form stones. The brownness is due to this mix of unconjugated
or hydrolyzed bilirubin and phospholipids. Some other common gallbladder infections are
Ascitris lumbricoides and clonorchis sinesis—the second of which is endemic to China, Korea,
and Vietnam, so brown-pigmented stones are commonly seen in Asian populations. Women are typically more at risk than men,
because estrogen increases cholesterol stone formation, which is also why use of oral contraceptive
pills that contain estrogen increase the risk of cholesterol stones. Also though, obesity is often associated with
increased levels of cholesterol, meaning that it’s also associated with increased risk
of cholesterol stones. Finally rapid weight-loss that decreases lipids
can create an imbalance in bile composition that increases the chances of calcium-bilirubin
precipitation and gallstone formation.

88 thoughts on “Gallstones (cholelithiasis) – causes, symptoms, diagnosis, treatment & pathology

Leave a Reply

Leave a Reply

Your email address will not be published. Required fields are marked *