Chapter 12: Cholestasis
Cholestasis = obstruction to bile flow, due to a stone in the CBD. Ex: have a cholesterol stone with a
deep green colored liver. Bile is blocked, which has conj bilirubin in it and is backed up into the liver.
The conj bilirubin will eventually reflux into the sinusoids, and leads to bilirubin in the urine and light
color stools, with NO urobilinogen in the urine. The yellow urine is due to water soluble conj
bilirubin in the urine. What enzymes are elevated? Alk phos and gamma glutamyl transferase.
What is the mech for getting rid of cholesterol? Bile. So, you reflux cholesterol, bilirubin and bile
salts (they are all recycled). Would it surprise you that they have hypercholesterolemia, too? No b/c
it is recycled. The bile salts deposit in the skin, leading to itching.
2 other causes of cholestasis:
Bile duct radical, surrounded by fibrous tissue, bloody diarrhea with LLQ crampy pain, jaundice –
what is the IBDz? UC
Common bile duct surrounded by fibrous tissue – dx? Primary sclerosing cholangitis. MCC
primary sclerosing cholangitis = UC
What cancer can develop b/c it involves the bile duct? Cholangiocarcinoma (MCC in this
country, in 3 world countries, it is due to Clonorchis sinensis – Chinese liver fluke).
Primary Biliary cirrhosis
50 y/o woman with generalized itching, find enlarged liver on PE, normal bilirubin (no jaundice), alk
phos and gamma glutamyl transferase are huge (obstructive type of enzymes), transaminases are
elevated – dx? Primary biliary cirrhosis, which is an autoimmune dz that leads to granulomatous
destruction of the bile ducts in the portal triad – why doesn’t she have jaundice? Let’s say you have
1 million triads, have the dz and knock off 250,000 of them. Still have 75% that can handle the
bilirubin load. 3 years later, only have 50% (500,000 destroyed). Still no jaundice, eventually, more
knocked off and get jaundice way down the line. So, the reason why pt won’t get jaundice is b/c pt
has a reserve that can handle the bilirubin. Therefore, there is no reason to have jaundice early and
it comes late. What is the Ab to order in this pt? Anti-mitochondrial antibodies (antimicrosomal =
Birth control (OCP) and anabolic steroid have the same effect on the liver. The OCP and anabolic
steroids both produce intrahepatic cholestasis. Ex. wt lifter (assume he’on steroids) develops
jaundice, and viral serology is negative, high alk phos and gamma glutamyl = due to steroids (not
hepatitis). One of the MCC’s jaundice in pregnancy is b9 intrahepatic cholestasis. This is b/c of the
estrogen during pregnancy, which produces intrahepatic cholestasis. Rx? Deliver baby (goes away
after delivering baby). Lets say woman takes OCP and gets jaundice; when she become pregnant,
she will develop jaundice, too b/c of the estrogen effect. So, intrahepatic cholestasis is a normal
complication of OCP’s and anabolic steroids. Both of these drugs also predispose to a b9 liver
tumor, called liver cell adenoma aka hepatic adenoma. It has a nasty habit – it likes to rupture,
leading to intraperitoneal hemorrhage (which can kill you). Example: wt lifter (assume he’s on
anabolic steroids) who is lifting and suddenly becomes hypotensive and collapses. Find abnormal
liver/cavity – what is most likely cause? Ruptured liver cell adenoma b/c pt is on anabolic steroids.
So, OCP’s and anabolic steroids have 2 similar effects: both can produce b9 intrahepatic
cholestasis (which goes away if you stop the drug) and liver cell adenoma which is susceptible to
rupture. For women, if they are on birth control, then get off it to get pregnant – let’s say they have
a liver cell adenoma they did not know about (that developed with OCP use), then get pregnant,
then get an intraperitoneal hemorrhage, and then what is d/d? Ruptured ectopic pregnancy or rupture intraperitoneal hemorrhage. Step 2: pregnant women have the tendency to have splenic
artery aneurysm = rupture.
Example: hyperpigmented pt – adult that is diffusely hyperpigmented and has diabetes (type I
diabetic) = bronze diabetes = hemochromatosis = Fe overload, auto rec, reabsorb too much Fe.
Hemosiderosis is acquired iron overload by being an alcoholic. Iron supplements are
contraindicated in the elderly b/c it will create hemosiderosis and have iron overload. Back to
hemochromatosis: it’s an autosomal recessive dz and what happens is that instead of reabsorbing
10-15% of iron from foods, you are absorbing 100% of iron. Target organ is the liver. Whenever Fe is
absorbed into cells, it produces hydroxyl free radicals. So, the Fe doesn’t damage anything, it’s the
free radicals (the hydroxyl free radicals –Fenton rxn). If you are damaging liver cells, will lead to
fibrosis and cirrhosis. They ALL