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,
got ta 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 are small amounts of other things like water, electrolytes, and bicarbonate.
还有少量的其他物质 比如水 电解质 碳酸氢盐
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.
胆盐呢 是阴离子形式 类似于这样
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
导致胆盐 胆汁酸 以及磷脂
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 or precipitates.
Another, somewhat similar way,
is if you don’t have enough of these bile acids or salts and
如果没有足够的胆盐 胆汁酸 磷脂
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 cholesterol to separate and basically precipitate out as a solid,
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
and on x-ray 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.
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 as well,
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.
OK quick breakdown of the structure of conjugated vs. unconjugated bilirubin:
好了 我们来快速分析一下结合胆红素和 非结合胆红素的结构：
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, right?
比正常时还要多 从而加速了非结合胆红素的产生 不是吗？
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, right?
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.
并且通常情况下 这类结石甚至会有可能脱出胆囊 进入胆管
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.
Also 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, right？
此外 肥胖通常也与胆固醇水平的升高有关 对吗？
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 gallstone formation.
When you eat some real fatty foods, like say some delicious french fries,