B5.025 Liver Disorders I

Question 1

primary diseases affecting the bile duct

Answer 1

PBC
PSC 
stones/ obstruction
abscess
congenital hepatic fibrosis/ polycystic liver disease
drug induced liver injury
cholangiocarcinoma

Question 2

describe a normal bile duct on histo

Answer 2

single layer of cuboidal epithelial cells

“string of pearls”

Question 3

lab values that evaluate hepatocyte integrity

Answer 3

AST/ALT

Question 4

lab values that evaluate biliary excretory function

Answer 4

serum bilirubin

plasma membrane proteins (alk phos, GGT)

Question 5

lab values that evaluate hepatocyte function

Answer 5

serum albumin
PT/INR
serum ammonia

Question 6

lab findings in obstructive liver disease pattern

Answer 6

increased alk phos, bilirubin GGT

Question 7

lab findings in acute hepatitis pattern

Answer 7

increased AST and ALT

Question 8

lab findings associated with cirrhosis pattern

Answer 8

decreased albumin, decreased platelets, prolonged PT

Question 9

what is cholestasis

Answer 9

impaired bile formation and bile flow

accumulation of bile pigment in hepatic parenchyma

Question 10

causes of cholestasis

Answer 10

extrahepatic obstruction of biliary tract
intrahepatic obstruction of biliary tract
defects in bile secretion

Question 11

etiologies of obstruction/obliteration of the bile ducts

Answer 11

cholelithiasis
cholangitis
PBC
PSC
postsurgical strictures
parasitic infection

Question 12

etiologies of compression of bile ducts outside the liver

Answer 12

pancreatic cancer
pancreatitis
extrahepatic biliary cancers

Question 13

appearance of bile plugs on histo

Answer 13

canalicular reddish inclusions

Question 14

other histo findings with cholestasis

Answer 14

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

Question 15

canals of hering

Answer 15

lead from intrahepatic bile ductile to canaliculi

lined by cells that can differentiate into duct cells or hepatocytes

Question 16

function of stellate cells

Answer 16

in case of inflammation, function as myofibroblasts and secrete type 1 and 3 collagen creating fibrosis

Question 17

alkaline phosphatase

Answer 17

present in bile duct epithelium and canalicular membrane of hepatocytes
released due to detergent action of retained bile salts on hepatocyte membrances

Question 18

signs and symptoms of cholestasis

Answer 18

jaundice
pruritis
skin xanthomas (accumulation of cholesterol)

Question 19

what is PBC?

Answer 19

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

Question 20

features of AMA in PBC

Answer 20

directed against M2 family of mitochondrial antigens–most frequent is E2 part of pyruvate dehydrogenase

Question 21

clinical presentation of PBC

Answer 21

90% female
peak 40-50 yo
elevated GGT and alk phos, minimal bili elevation at first, minimal AST/ALT elevation

Question 22

histopath findings with PBC

Answer 22

destructive (non-suppurative) cholangitis
florid duct lesions
histo evidence of bile duct damage
granulomas in portal tract
lobules of PBC are nearly normal

Question 23

elaborate on features of histo evidence of bile duct damage

Answer 23

disruption of BM
intraepithelial lymphs and plasma cells
cytoplasmic vacuolization
regenerative hyperplasia
occasional mitoses

Question 24

what is a florid duct lesion

Answer 24

aggregation of unusual cells and disrupted membranes

Question 25

what does a damaged duct look like?

Answer 25

irregular epithelial cells , no string of pearls appearance | fibrosis

Question 26

treatment of PBC

Answer 26

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

Question 27

features of PSC

Answer 27

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%

Question 28

appearance of p-ANCA on fluorescent microscopy

Answer 28

illumination around multi-lobed neutrophil nuceli

Question 29

evidence of immunologically mediated injury in PSC

Answer 29

T cells in periductal stroma presence of circulating autoAb (p-ANCA) association with HLA-B8 and other MHC antigens

Question 30

discuss the linkage between PSC and UC

Answer 30

T cells activated in damaged mucosa of patients with UC migrate to liver and recognize a cross reacting bile duct antigen

Question 31

findings in PSC

Answer 31

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"

Question 32

histopath findings in PSC

Answer 32

fibrous cholangitis adjacent mixed inflammatory infiltrate lesions are focal, patchy (can lead to a negative biopsy) can have ductopenia without ductal scars

Question 33

clinical sequelae of PSC

Answer 33

acute bouts of ascending cholangitis persistent alk phos elevation 25% develop cholelithiasis lifetime risk of cholangiocarcinoma =20%

Question 34

possible etiologies of large duct obstruction

Answer 34

gallstones malignancy of biliary tree or head of pancreas stricture from previous surgery kids: biliary atresia, CF, choledochal cysts, insufficient bile ducts

Question 35

ascending cholangitis

Answer 35

secondary bacterial infections enteric organisms (enterococci, E.coli) suppurative cholangitis fever, chills, ab pain, jaundice

Question 36

histo features of large duct obstruction

Answer 36

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

Question 37

what is cholestasis of sepsis

Answer 37

direct effects of intrahepatic bacterial infection ischemia relating to hypotension caused by sepsis circulating microbial products inhibit biliary secretions

Question 38

most well known drugs with liver toxicity

Answer 38

``` antibiotics psychotropics anticonvulsants oral contraceptives anti-inflammatories ```

Question 39

features of predominantly cytolytic acute injury

Answer 39

spotty necrosis submassive necrosis massive necrosis (APAP, psychotropics, herbal meds, cocaine, carbon tetrachloride)

Question 40

features of predominantly cholestatic acute injury

Answer 40

``` intrahepatic cholestasis (mostly in centrilobular hepatocytes, formation of canalicular plugs) anabolic or contraceptive steroid use ```

Question 41

what are choledochal cysts

Answer 41

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

Question 42

what are fibropolycystic diseases

Answer 42

congenital malformations of biliary tree: von meyenburg complexes-small bile duct hamartomas polycystic liver disease caroli disease congenital hepatic fibrosis

Question 43

what do von meyenburg complexes look like on histo

Answer 43

branching profiles from bile ducts | lots of fibrosis

Question 44

formation of cholesterol stones

Answer 44

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

Question 45

formation of pigment stones

Answer 45

complex mixture of abnormal insoluble calcium salts and unconjugated bilirubin form w/ and increase in bilirubin or infection of the biliary tract

Question 46

clinical features of stones

Answer 46

majority are asymptomatic colicky pain smaller stones cause more pain

Question 47

risk factors for cholangiocarcinoma

Answer 47

PSC congenital fibropolycystic diseases previous exposure Thorotrast (old biliary tree contrast) opisthorchis sinesis (liver fluke)

Question 48

features of cholangiocarcinoma

Answer 48

``` poor prognosis (median survival 6 months) adenocarcinoma ```

Question 49

histo features of cholangiocarcinoma

Answer 49

pleomorphic- all cells look different