B5.025 Liver Disorders I Flashcards
primary diseases affecting the bile duct
PBC PSC stones/ obstruction abscess congenital hepatic fibrosis/ polycystic liver disease drug induced liver injury cholangiocarcinoma
describe a normal bile duct on histo
single layer of cuboidal epithelial cells
“string of pearls”
lab values that evaluate hepatocyte integrity
AST/ALT
lab values that evaluate biliary excretory function
serum bilirubin
plasma membrane proteins (alk phos, GGT)
lab values that evaluate hepatocyte function
serum albumin
PT/INR
serum ammonia
lab findings in obstructive liver disease pattern
increased alk phos, bilirubin GGT
lab findings in acute hepatitis pattern
increased AST and ALT
lab findings associated with cirrhosis pattern
decreased albumin, decreased platelets, prolonged PT
what is cholestasis
impaired bile formation and bile flow
accumulation of bile pigment in hepatic parenchyma
causes of cholestasis
extrahepatic obstruction of biliary tract
intrahepatic obstruction of biliary tract
defects in bile secretion
etiologies of obstruction/obliteration of the bile ducts
cholelithiasis cholangitis PBC PSC postsurgical strictures parasitic infection
etiologies of compression of bile ducts outside the liver
pancreatic cancer
pancreatitis
extrahepatic biliary cancers
appearance of bile plugs on histo
canalicular reddish inclusions
other histo findings with cholestasis
small bile ducts form all around main bile duct outside of portal triad to try to compensate backed up flow
bile is chemotactic for neutrophils, so inflammatory infiltrates
canals of hering
lead from intrahepatic bile ductile to canaliculi
lined by cells that can differentiate into duct cells or hepatocytes
function of stellate cells
in case of inflammation, function as myofibroblasts and secrete type 1 and 3 collagen creating fibrosis
alkaline phosphatase
present in bile duct epithelium and canalicular membrane of hepatocytes
released due to detergent action of retained bile salts on hepatocyte membrances
signs and symptoms of cholestasis
jaundice
pruritis
skin xanthomas (accumulation of cholesterol)
what is PBC?
chronic bile duct destructive disease autoimmune disease aberrant expression of MHC class II molecules on bile duct epithelial cells and autoreactive T cells around ducts AMA is increased
features of AMA in PBC
directed against M2 family of mitochondrial antigens–most frequent is E2 part of pyruvate dehydrogenase
clinical presentation of PBC
90% female
peak 40-50 yo
elevated GGT and alk phos, minimal bili elevation at first, minimal AST/ALT elevation
histopath findings with PBC
destructive (non-suppurative) cholangitis florid duct lesions histo evidence of bile duct damage granulomas in portal tract lobules of PBC are nearly normal
elaborate on features of histo evidence of bile duct damage
disruption of BM intraepithelial lymphs and plasma cells cytoplasmic vacuolization regenerative hyperplasia occasional mitoses
what is a florid duct lesion
aggregation of unusual cells and disrupted membranes
what does a damaged duct look like?
irregular epithelial cells , no string of pearls appearance
fibrosis
treatment of PBC
oral UDCA
slow progression
mechanism is uncertain, but is presumably related to ability of UDCA to enter bile acid pool and alter composition of bile
features of PSC
involvement of extrahepatic and intrahepatic biliary tree
M:F = 2:1, 20-40 yrs
70-80% of pts also have ulcerative colitis
p-ANCA in 80%
appearance of p-ANCA on fluorescent microscopy
illumination around multi-lobed neutrophil nuceli
evidence of immunologically mediated injury in PSC
T cells in periductal stroma
presence of circulating autoAb (p-ANCA)
association with HLA-B8 and other MHC antigens
discuss the linkage between PSC and UC
T cells activated in damaged mucosa of patients with UC migrate to liver and recognize a cross reacting bile duct antigen
findings in PSC
increased GGT and alk phos
mild increase in AST/ALT and bilirubin
beaded areas of bile ducts on ERCP
progressive concentric periductal fibrosis “onion skin”
histopath findings in PSC
fibrous cholangitis
adjacent mixed inflammatory infiltrate
lesions are focal, patchy (can lead to a negative biopsy)
can have ductopenia without ductal scars
clinical sequelae of PSC
acute bouts of ascending cholangitis
persistent alk phos elevation
25% develop cholelithiasis
lifetime risk of cholangiocarcinoma =20%
possible etiologies of large duct obstruction
gallstones
malignancy of biliary tree or head of pancreas
stricture from previous surgery
kids: biliary atresia, CF, choledochal cysts, insufficient bile ducts
ascending cholangitis
secondary bacterial infections
enteric organisms (enterococci, E.coli)
suppurative cholangitis
fever, chills, ab pain, jaundice
histo features of large duct obstruction
distention of upstream bile ducts leading to bile duct dilatation
ductular proliferation at portal-parenchymal interface (canals of Hering)
periductular neutrophils
bile infarcts and bile lakes
what is cholestasis of sepsis
direct effects of intrahepatic bacterial infection
ischemia relating to hypotension caused by sepsis
circulating microbial products inhibit biliary secretions
most well known drugs with liver toxicity
antibiotics psychotropics anticonvulsants oral contraceptives anti-inflammatories
features of predominantly cytolytic acute injury
spotty necrosis
submassive necrosis
massive necrosis
(APAP, psychotropics, herbal meds, cocaine, carbon tetrachloride)
features of predominantly cholestatic acute injury
intrahepatic cholestasis (mostly in centrilobular hepatocytes, formation of canalicular plugs) anabolic or contraceptive steroid use
what are choledochal cysts
congenital dilatation of common bile duct
most present in kids <10yrs with jaundice and ab pain
F:M = 3-4:1
increased risk of stones, strictures, stenosis, obstructive biliary complications, bile duct carcinoma
what are fibropolycystic diseases
congenital malformations of biliary tree:
von meyenburg complexes-small bile duct hamartomas
polycystic liver disease
caroli disease
congenital hepatic fibrosis
what do von meyenburg complexes look like on histo
branching profiles from bile ducts
lots of fibrosis
formation of cholesterol stones
cholesterol must be made soluble in bile, aggregation with water soluble bile salts which act as detergents
when cholesterol concentration exceeds solubilizing capacity of bile solid crystals of cholesterol form
free cholesterol is toxic to gallbladder
formation of pigment stones
complex mixture of abnormal insoluble calcium salts and unconjugated bilirubin
form w/ and increase in bilirubin or infection of the biliary tract
clinical features of stones
majority are asymptomatic
colicky pain
smaller stones cause more pain
risk factors for cholangiocarcinoma
PSC
congenital fibropolycystic diseases
previous exposure Thorotrast (old biliary tree contrast)
opisthorchis sinesis (liver fluke)
features of cholangiocarcinoma
poor prognosis (median survival 6 months) adenocarcinoma
histo features of cholangiocarcinoma
pleomorphic- all cells look different
