Cholestatic liver disease
is a medication that decreases the cholesterol content of bile used in children with chronic cholestatic disease to increase bile formation.
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A 26-year-old woman, who is at 30 weeks gestation, comes to a dermatology clinic because of "itchy skin." The patient states that the itching began over the past two weeks. She has not noticed any skin lesions but has been picking at and scratching her skin with her nails. Physical examination shows faint red and pink excoriations, but no primary skin lesions. A disorder involving which of the following organs is most likely responsible for her skin condition?
Content Reviewers:Rishi Desai, MD, MPH, Tanner Marshall, MS, Tanner Marshall, MS, Tanner Marshall, MS, Vincent Waldman, PhD
For healthy humans, bile usually flows from the liver and into the small intestine, and this is a super important part of digestion and absorption of nutrients.
When there isn’t enough bile flowing between these two, we can say that there’s some sort of cholestasis going on, because chole- means bile and -stasis means inactivity.
This reduction in bile flow can basically be split into two types, hepatocellular cholestasis, where for some reason the hepatocytes aren’t making enough bile, and obstructive cholestasis, where something’s physically blocking bile flow.
And in this case, hepatocytes literally can’t pump out the cholic acid, because it’s been found that estrogen inhibits the export pump that usually moves the bile acid from the hepatocyte to the bile canaliculi, which leads to the bile ductules and eventually the common hepatic duct.
But bile acids are just one component of bile, right? Wouldn’t the bile still be made, just without the bile acids?
Well, production and secretion of bile acids is a major driving force for the synthesis of bile in the hepatocytes, so when the cells can’t transport the bile acids and so they build up inside the cells, and this is basically a signal to down-regulate bile acid synthesis and excretion of bile altogether, which decreases the total amount of bile production.
When excretion of bile components like conjugated bilirubin are down, but they’re still being conjugated, they also build up along with the bile acids, and eventually, it’s thought that they diffuse or are exocytosed into the interstitial space, where it can access the blood supply.
Unfortunately, this can be a dangerous situation for the fetus because maternal bile acids can cross the placenta and buildup in the fetal compartment.
This can lead to an increased risk of stillbirth after 37 weeks of gestation.
Anabolic steroids, like those used by athletes or body-builders, have also been linked to cholestasis, it’s thought because they’re similar in structure to estrogen, though the mechanisms aren’t very well-known.
In newborns, it’s thought that several of the important mechanisms that help produce bile in hepatocytes are relatively immature, leading to an overall decreased ability to produce bile, and this, in combination with the developing liver being more sensitive to injury, can lead to a reduction in bile synthesis and bile flow.
Now this is usually a physical blockage of the common bile duct, and there are some common causes.
It could be like a gallstone that came from the gallbladder, or it could be from a disease called primary sclerosing cholangitis, where the body’s immune system attacks the bile ducts causing inflammation and scar tissue buildup, which can make it more difficult for bile to flow through them.
Finally, pancreatic carcinomas that grow at the head of the pancreas may also physically block flow of bile, since the common bile duct moves through the head of the pancreas.
This buildup of bile will be pretty obvious on histology of the liver, and will look like these “bile lakes” or “bile infarcts”, which are these pools of yellowish-green bile that has made their way into the interstitial space.