PSC and PBC Flashcards
Describe the natural history of primary sclerosing cholangitis.
bile duct injury characterized by inflammation, fibrosis, and strictures; often in young men, usually before 45yo, relatively rare
generally a slow progression to secondary biliary cirrhosis, portal HTN and liver failure
7-15% will develop cholangiocarcinoma
Describe the pathogenesis of PSC
autoimmune destruction of ducts, elevated immunoglobulins and autoantibodies form circulating immune complexes that cross react with biliary and colonic epithelium; some evidence for genetic predisposition and increased bacterial infiltration from portal circulation (initiation of T-cell reactivity)
ischemic disease can contribute
(80-90% have pANCA)
What conditions are associated with PSC?
75% have ulcerative colitis, 5% have Crohn’s
What is the clinical presentation of PSC
> 10% are asymptomatic
fatigue, weight loss, abdominal pain
pruritis (25-60%), episodic jaundice (30-70%)
rare acute cholangitis
What clinical findings confirm PSC?
ERCP showing multifocal strictures with intervening normal/dilated ducts
ALKP 2x normal, elevated transaminases, bilirubin, PT, low albumin as disease progresses
pathological lesion is onion ring lesion around the bile duct due to inflammation (concentric fibrosis with surrounding inflammatory infiltrate)
How do you treat PSC?
supportive care only- no intervention has slowed progression
endoscopy can be used to remove stones and dilated strictures (delays time to transplant)
definitive treatment is transplant
Cholangiocarcinoma is signifantly linked to _____ and viral infection of the hepatocytes, and presentation in the ____ ducts has a worse prognosis than _____ ducts.
significantly linked to heavy alcohol and viral infection
worse in intrahepatic ducts than extra hepatic
(70% when multimodality therapy of surgery chemo and radiation used)
Name risk factors for cholangiocarcinoma.
ongoing inflammation PSC gallstones liver flukes cysts (congenital) toxic exposure
presents in 6th or 7th decade, men
What is the presentation of cholangiocarcinoma? How do you confirm diagnosis?
non specific weight loss, anorexia, abdominal pain, failure to thrive, new onset or worsening LFTs jaundice
serum tumor markers CEA CA19-9, CT scan, MRC, definitive test is ERCP, difficult to diagnose with longstainc PSC
Only _____ of proximal tumors and 60-70% of distal tumors are resectable.
20-30%, invasion of both lobes, major vessels make tumor unresectable, palliative endoscopic or percutaneous stenting possible
Define primary biliary cirrhosis.
progressive chronic cholestatic autoimmune disease that affects the small intrahepatic bile ducts
90% women, caucasian, 6th and 7th decade
What is the pathophysiology of PBC?
injury due to CTL mediated autoimmune destruction of epithelial cells of small bile ducts in lobule, arising in a susceptible individual as a result of exposure to some environmental stimulus
associated antimitochondrial antibodies (AMA), IgM hypergammaglobulinemia
chronic damage leads to obstruction of bile flowing cholestasis
What are the clinical signs of PBC?
50% asymptomatic at time of diagnosis
fatigue and pruritus is very significant,
jaundice is a sign of disease progression
elevated AlkP, elevate bilirubin (progressive disease), positive AMA and hypergammaglobinemia
liver biopsy confirms with patchy destruction of interlobular bile ducts with mononuclear infiltrate and possible granulomas
What are the metabolic sequelae of PBC?
weight loss, steatorrhea and vitamin deficiencies due to low bile secretion
bone disease because of vit D. malabsorption
What is the course of PBC? What is the greatest predictor of survival?
variable with wide spectrum , generally slow progressive disease (some asympt with normal lifespan)
bilirubin is the greatest predictor of survival?