Cirrhosis Flashcards
What does chronic liver disease look like on histo?
(regardless of injury, viral, etoh… all can result in cirrhosis)
Chronic inflammation of hepatic parenchyma w/ lymphocytes causes “bridging necrosis” between portal tracts and portal tracts to termincal hepatic veins…
What kinds of problems can cause cirrhosis?
alcohol abuse, viral hepatitis, non-alcoholic steatohepatitis (NASH)… PSC and primary biliary cirrhosis, also hemochromatosis
Why is cirrhosis a big deal? aka what is the pathophys?
the bridging fibrous septa form bands which link portal tracts with each other and portal tracts with terminal hepatic veins… so the “bridging septa” form vascular interconnections that allow blood to skip the hepatocytes…
Thus toxins don’t get removed and go to the heart etc (esp ammonia) AND this fibrosis presses on vessels causes portal HTN…
It is fibrosis that is the key feature of progressive damage to liver on histo!!!
Why are nodules formed in cirrhosis?
Nodularity results from cycles of hepatocyte regeneration through extensive fibrosis…
What is the role of types I and III collagen in cirrhosis?
they get deposited in the space of Disse, creating fibrotic septal tracts… NEW vasculature occurs in these tracts thus blood is no longer being detoxified!… collagen deposition in the space of disse will also disrupt the sinusoids
What causes portal hypertension?
Cirrhosis accounts for most cases of portal HTN… the fibrosis compresses portal vein at the level of the sinusoids…
What would you clinically see in portal HTN?
1) ascites
2) portosystemic venous shunts (esophageal, anal, umbilical shunts)
3) congestive splenomegaly
4) hepatic encephalopathy (cannot remove ammonia!)
What are some important histopathologic features of Hep C?
1) portal tract inflammation w/ lymphocytes
2) steatosis
What does hep B look like on histo?
very little inflamm response (unlike hep C)
GROUND GLASS hepatocytes w. HBsAg in endoplasmic reticulum
What are the 3 phases of alcoholic liver disease?
1) hepatic steatosis (fatty liver = reversible!)
2) alcoholic hepatitis (somewhat reversible)
3) cirrhosis
Is alcoholic steatosis rare? what is the difference between a few drinks and drinking all the time?
NOPE! even after a few drinks you get microvesicular lipid droplet accumulation
w. chronic intake, large macrovesicular globules compress and displace the hepatocyte nucleus to the periphery of the cell!
Is fatty change permanent?
NOPE! if you stop drinking this completely will go away
Why does fat accumulate w/ alcohol anyways?
W/ alcohol ingestion, alcohol dehydrogenase and aldehyde dehydrogenase cause an increase in NADH+ thus shunting metabolism toward lipid biosynthesis!… NADH+ also decreases ability of liver to undergo gluconeogenesis.
How is alcoholic hepatitis (stage 2) different from alcoholic alcoholic steatosis?
Hepatocyte swelling (ballooning) and necrosis occurs!
*Mallory bodies form!
neutrophils come in
ACTIVATION OF sinusoidal stellate cells, and portal tract fibroblasts –> FIBROSIS!
What are mallory bodies? and what stage of alcoholic liver disease do they present?
scattered hepatocytes that accumulate tangled cytokeratin in complex w. other proteins like ubiquitin
They are typically specific to stage 2 (alcoholic hepatitis)
What are some characteristics of alcoholic cirrhosis?
IRREVERSIBLE!
the regenerating hepatocytes have to poke through the existing fibrosis –> “islands” or “nodules” causing a “hobnail” appearance
What might be a clinical hint of alcoholic liver disease progression in your alcoholic patient?
acute esophageal bleeding! cirrhosis –> portal hypertension –> shunting –> esophageal varices!
What is non-alcoholic fatty liver disease and how is it different from alcoholic steatosis?
occurs w/ little or no alcohol use
MOST COMMON cause of chronic liver disease in U.S.
Precise mechanism is unknown
It also shows hepatocellular ballooning, lobular inflammation and steatosis… can progress to fibrosis
Who gets non-alc fatty acid liver disease?
strongly associated with obesity and those with metabolic syndrome
Can you get cancer from non-alc fatty liver disease?
yes… can cause hepatocellular carcinoma
What is the histologic hallmark of steatohepatitis? (betw steatosis and hepatitis)
Pericellular fibrosis w/ “branching out” pattern
What are the 3 most important things i should know about autoimmune hepatitis? and how is it treated?
1) Predominantly in women (78%)
2) Has anti-nuclear antibodies (ANA) and/or Anti-smooth muscle antibodies!
3) Clusters of PLASMA cells in the portal tracts and hepatic lobules
Tx = prednisone alone or combined with azathioprine
(cirrhosis develops in approximately 40% of survivors
Who gets primary biliary cirrhosis and how is it diagnosed?
typically in middle-aged women who present w/ fatigue
- serum AP and cholesterol are almost always elevated
- Anti-mitochondrial antibodies* present in 90-95% of patients!
What is primary biliary cirrhosis?
autoimmune inflammatory disease mainly affecting the intrahepatic bile ducts –> cholestasis (so it can sometimes cause conjugated hyperbilirubinemia)
-*eventually cirrhosis develops! after many years
What is the buzzword for primary biliary cirrhosis on histology?
granulomas + Duct destruction! esp in the presence of anti-mitochondrial antibodies!
What is primary sclerosis cholangitis?
Chronic cholestatic disorder characterized by non-specific inflammation, fibrosis, and strictures of both intra-hepatic and extra-hepatic bile ducts.
What blood tests are typical of PSC? (3 of em)
anti-nuclear antibodies (ANA)
rheumatoid factor
atypical p-ANCA
PSC is also commonly associated with what other intestinal autoimmune disorder?
Ulcerative Colitis
What is the hallmark buzzword for PSC on radiology?
“beading” of contrast medium in radiographs of intrahepatic and extrahepatic biliary tree
What does histology look like on PSC?
it is a fibrosing cholangitis of bile ducts, with a lymphocytic infiltrate, progressive atrophy of bile duct epithelium and narrowing/obliteration of bile duct lumen
onion-skin fibrosis (liver looks green due to bile back-up)
What is the course of PSC like?
Follows a protracted course of 5 to 17 years
Approximately 7% pts with PSC develop cholangiocarcinoma
What are the 2 main associations to make in patients w. alpha 1 antitrypsin deficiency?
1) pt will likely also have COPD
2) causes cytoplasmic inclusions in histology
What is hereditary hemochromatosis and what is the mutation that causes it?
a net iron accumulation of about 1 gram per year in the liver… (therefore women present later)
The mutation is in the HFE gene on short arm of chromosome 6
What is the clinical presentation that is characteristic of hemochromatosis?
BRONZE diabetes: dark skin pigmentation and insulin resistance
What stain would you want to use on a liver biopsy sample of a person with suspecte hemochromatosis?
Prussian Blue! (stains for iron)
