Cirrhosis

Question 1

What does chronic liver disease look like on histo?

Answer 1

(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…

Question 2

What kinds of problems can cause cirrhosis?

Answer 2

alcohol abuse, viral hepatitis, non-alcoholic steatohepatitis (NASH)… PSC and primary biliary cirrhosis, also hemochromatosis

Question 3

Why is cirrhosis a big deal? aka what is the pathophys?

Answer 3

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!!!

Question 4

Why are nodules formed in cirrhosis?

Answer 4

Nodularity results from cycles of hepatocyte regeneration through extensive fibrosis…

Question 5

What is the role of types I and III collagen in cirrhosis?

Answer 5

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

Question 6

What causes portal hypertension?

Answer 6

Cirrhosis accounts for most cases of portal HTN… the fibrosis compresses portal vein at the level of the sinusoids…

Question 7

What would you clinically see in portal HTN?

Answer 7

1) ascites
2) portosystemic venous shunts (esophageal, anal, umbilical shunts)
3) congestive splenomegaly
4) hepatic encephalopathy (cannot remove ammonia!)

Question 8

What are some important histopathologic features of Hep C?

Answer 8

1) portal tract inflammation w/ lymphocytes

2) steatosis

Question 9

What does hep B look like on histo?

Answer 9

very little inflamm response (unlike hep C)

GROUND GLASS hepatocytes w. HBsAg in endoplasmic reticulum

Question 10

What are the 3 phases of alcoholic liver disease?

Answer 10

1) hepatic steatosis (fatty liver = reversible!)
2) alcoholic hepatitis (somewhat reversible)
3) cirrhosis

Question 11

Is alcoholic steatosis rare? what is the difference between a few drinks and drinking all the time?

Answer 11

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!

Question 12

Is fatty change permanent?

Answer 12

NOPE! if you stop drinking this completely will go away

Question 13

Why does fat accumulate w/ alcohol anyways?

Answer 13

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.

Question 14

How is alcoholic hepatitis (stage 2) different from alcoholic alcoholic steatosis?

Answer 14

Hepatocyte swelling (ballooning) and necrosis occurs!

*Mallory bodies form!

neutrophils come in

ACTIVATION OF sinusoidal stellate cells, and portal tract fibroblasts –> FIBROSIS!

Question 15

What are mallory bodies? and what stage of alcoholic liver disease do they present?

Answer 15

scattered hepatocytes that accumulate tangled cytokeratin in complex w. other proteins like ubiquitin

They are typically specific to stage 2 (alcoholic hepatitis)

Question 16

What are some characteristics of alcoholic cirrhosis?

Answer 16

IRREVERSIBLE!
the regenerating hepatocytes have to poke through the existing fibrosis –> “islands” or “nodules” causing a “hobnail” appearance

Question 17

What might be a clinical hint of alcoholic liver disease progression in your alcoholic patient?

Answer 17

acute esophageal bleeding! cirrhosis –> portal hypertension –> shunting –> esophageal varices!

Question 18

What is non-alcoholic fatty liver disease and how is it different from alcoholic steatosis?

Answer 18

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

Question 19

Who gets non-alc fatty acid liver disease?

Answer 19

strongly associated with obesity and those with metabolic syndrome

Question 20

Can you get cancer from non-alc fatty liver disease?

Answer 20

yes… can cause hepatocellular carcinoma

Question 21

What is the histologic hallmark of steatohepatitis? (betw steatosis and hepatitis)

Answer 21

Pericellular fibrosis w/ “branching out” pattern

Question 22

What are the 3 most important things i should know about autoimmune hepatitis? and how is it treated?

Answer 22

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

Question 23

Who gets primary biliary cirrhosis and how is it diagnosed?

Answer 23

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!

Question 24

What is primary biliary cirrhosis?

Answer 24

autoimmune inflammatory disease mainly affecting the intrahepatic bile ducts –> cholestasis (so it can sometimes cause conjugated hyperbilirubinemia)

-*eventually cirrhosis develops! after many years

Question 25

What is the buzzword for primary biliary cirrhosis on histology?

Answer 25

granulomas + Duct destruction! esp in the presence of anti-mitochondrial antibodies!

Question 26

What is primary sclerosis cholangitis?

Answer 26

Chronic cholestatic disorder characterized by non-specific inflammation, fibrosis, and strictures of both intra-hepatic and extra-hepatic bile ducts.

Question 27

What blood tests are typical of PSC? (3 of em)

Answer 27

anti-nuclear antibodies (ANA)
rheumatoid factor
atypical p-ANCA

Question 28

PSC is also commonly associated with what other intestinal autoimmune disorder?

Answer 28

Ulcerative Colitis

Question 29

What is the hallmark buzzword for PSC on radiology?

Answer 29

“beading” of contrast medium in radiographs of intrahepatic and extrahepatic biliary tree

Question 30

What does histology look like on PSC?

Answer 30

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)

Question 31

What is the course of PSC like?

Answer 31

Follows a protracted course of 5 to 17 years

Approximately 7% pts with PSC develop cholangiocarcinoma

Question 32

What are the 2 main associations to make in patients w. alpha 1 antitrypsin deficiency?

Answer 32

1) pt will likely also have COPD

2) causes cytoplasmic inclusions in histology

Question 33

What is hereditary hemochromatosis and what is the mutation that causes it?

Answer 33

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

Question 34

What is the clinical presentation that is characteristic of hemochromatosis?

Answer 34

BRONZE diabetes: dark skin pigmentation and insulin resistance

Question 35

What stain would you want to use on a liver biopsy sample of a person with suspecte hemochromatosis?

Answer 35

Prussian Blue! (stains for iron)