Primary sclerosing cholangitis
Primary sclerosing cholangitis is a liver disorder that involves inflammation and "onion skin" fibrosis of bile ducts.
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A 40-year-old woman comes into the emergency department because of increasing fatigue over the past two weeks. She reports feeling ill a few weeks ago with fever, chills, and abdominal pain. Her temperature is 37.9°C (100.2°F), pulse is 75/min, respirations are 15/min, and blood pressure is 120/85 mm Hg. Physical exam shows no abnormalities. Serum aminotransferase concentration is 290 U/L, and serum alkaline phosphatase is 100 U/L. Cholangiography shows multifocal stricturing and dilation of both the intrahepatic and extrahepatic bile ducts. Which of the following may also be associated?
The name “primary sclerosing cholangitis” or PSC, is actually pretty straightforward, primary refers to it not being known to have been caused by anything else, in other words it isn’t secondary to something else.
Sclerosing means hardening of the tissue and cholangitis is inflammation of the bile ducts.
So with PSC we have this fibrosis and inflammation of both the intra- and extra-hepatic ducts, so inside and outside the liver.
As these cells around the bile ducts become inflamed, die, and harden due to fibrosis, you get this like tightening of the ducts in some areas where there’s been serious fibrosis, and then dilation in other areas that aren’t as affected, and this leads to the classic PSC finding of this sort of “beaded” appearance of the bile ducts.
These areas of fibrosis in the bile ducts can also be seen on histology, and looks a bit like an onion skin since you’ve got these concentric rings of fibrosis around the bile duct, so sometimes it’s referred to as “onion-skin fibrosis”.
Again, with PSC, we don’t really know what causes it right? One clue though is that it’s been known to be associated with ulcerative colitis which is an autoimmune disease and crohn’s disease which is immune-system related; knowing that, PSC’s thought to possibly be an autoimmune disorder itself involving the immune system’s T cells attacking and destroying bile duct epithelial cells.
Why they might start doing this, though, is not very well known, and likely happens in people with certain genetic predispositions when they’re exposed to some specific stimuli in their environment.
Certain genetic factors have been linked to developing PSC; studies have shown that patients with PSC tend to have in common specific human leukocyte antigens, or HLAs.
HLAs are these specific markers on cells that tell your body whether these cells are your own cells or someone else’s cells, and sometimes, for reasons that are usually not well known, the body’s immune system might think that certain HLAs or cell surface markers are foreign even when they’re your own, leading to an autoimmune disorder.
Specific HLA’s that have been common among people with PSC are HLA-B8, HLA-DR3, and HLA-DRw52a.
Another piece of supporting evidence for the autoimmune theory is that most patients with PSC have elevated IgM antibody levels in the serum, as well as an antibody called p-ANCA.
P-ANCA stands for perinuclear anti-neutrophil cytoplasmic antibody, so this is a specific antibody that targets antigens in the cytoplasm or nucleus of neutrophils, the perinuclear part means that the antibody targets an antigen around the nucleus.
Here’s an immunofluorescent image of p-ANCAs, the antibodies in this image are shown in orange, and notice they’ve sort of aggregated around the nucleus, meaning that they bind to an antigen around the nucleus.
A very high proportion, as high as 80%, of patients with PSC have this p-ANCA staining pattern.
Symptoms of PSC are similar to the symptoms of obstructive jaundice, since these “beads” or pinched areas are obstructing the flow of bile.
Also, as these epithelial cells lining the ducts die off, bile can now be allowed to leak out past the cells into the interstitial space, where it can access the bloodstream.