Liver Path 2 - Nelson

Question 1

What is the hepatic disease characterized by diffuse interconnecting fibrous scars?

Answer 1

Cirrhosis

Most commonly caused by alcoholic liver disease

Question 2

What’s the most common cause of portal hypertension?

Complications of portal hypertension?

Answer 2

Cirrhosis

Complications:
Esophageal Varices
Ascites
Splenomegaly
Hepatic Encephalopathy

Question 3

What biopsy finding do you see in a patient with alcoholic hepatitis?

Answer 3

Mallory Bodies and neutrophilic inflammation

Question 4

From the name you know that Non-alcoholic fatty liver disease is not causes by alcohol… so who gets it?

Answer 4

Those with metabolic syndrome (Obesity, type 2 diabetes, insulin resistance)

Pathologically it has to do with insulin resistance resulting in lipid accumulation and oxidative injury

Question 5

A 45 year old woman comes into your family practice clinic. She is of Northern European ancestry, doncha know? She says she has slowly gotten more and more tired and claims she is really itchy lately…

What key diagnostic tests do you need to order?

Answer 5

This could possibly be Primary Biliary Cirrhosis! (This is an autoimmune destruction of intrahepatic bile ducts)

Tests:
AMA (Antimitochndrial Antibody) - specific for this disease

Elevated alkaline phosphatase and GGT will also be elevated and help you decide to get an AMA

Question 6

A 40 year old patient with Ulcerative Colitis began having more fatigue and pruritis. You don’t think much of it until you notice that he has an elevated alkaline phosphatase… You decide to do a choliangiography and see a beaded presentation of intra- and extra-hepatic bile ducts.

What does he have doc?
Tx?

Answer 6

Sounds like he has PSC - Primary Sclerosing Cholangitis

There is not effective therapy.

Question 7

After secretly sequencing your own genome in the lab you work in, you discover that you have homozygous mutation in C282Y, a common HFE mutation.

What disease is associated with this mutation?
Pathophysiology?
Why didn’t you ever know?

Answer 7

Associate with hereditary hemochromatosis

Defect results in decreased hepcidin synthesis, leading to excessive iron absorption from gut

Disease has a low penetrance, so you are not expressing the phenotype despite having the genetic trait

Question 8

Symptoms and treatment for hemochromatosis?

Answer 8

Clinical triad - cirrhosis, diabetes, skin pigmentation (bronze diabetes)

Biopsy with iron will conform diagnosis

Treatment is phlebotomy or iron-chelators

Question 9

You are trying to figure out if a patient has hereditary or secondary hemochromatosis… Biopsy shows that the iron is accumulating in kupffer cells rather than periportally.
So which is it?

Answer 9

Secondary hemochromatosis will accumulate iron in Kupffer cells.

Happens in parenteral iron overload, dyserythropoesis, excessive oral intake of iron, alcoholic liver disease

Question 10

A 16 year old girl presents with liver disease.

On eye exam you notice Kayser-Fleischer rings on her corneas.
What diagnostic testing can you perform to decide if she has the disease that should already have popped into your head?
Including DNA test…

Answer 10

Wilson’s Disease!

Dx Tests

• Ceruloplasmin typically low
• 24 hr urine copper excretion increaed
• Overall serum copper low (due to low ceruloplasmin)
• Genetic tests available for ATP7B gene

(ATP7B produces a protein to get copper out of liver)

Question 11

Alpha1Antitrypsin is an important genetic component of both emphysema and liver disease.
In emphysema pathology occurs due to the imbalance between A1AT and neurtophil elastase, however in liver disease it is caused by:

Answer 11

Accumulation of A1AT in hepatocytes

On biopsy you will see cytoplasmic globular inclusions

Question 12

We all now you shouldn’t get aspirin to kids because it could result in Reye’s syndrome following viral illness. Here’s a review question: What disease might be a real good reason to give a child aspirin?

Answer 12

Kawasaki Disease

This disorder occurs mainly in kids under 5 and results in vasculitis of medium-sized blood vessels. It can cause fatal myocardial aneurisms!

Question 13

Explain the rationale behind this statement:

AST:ALT ratio over 2 suggest alcoholic liver disease

Answer 13

ALT and AST are both liver function tests - ALT is more specific to only liver.

AST is found in mitochondria and alcohol is toxic to mitochrondia. So this disease is going to cause a BIG elevation in AST

Question 14

What do you use alkaline phosphatase and GGT for?

Answer 14

They are markers of cholestasis!
With their powers combined!!!

Alkaline phosphatase usually elevates in response to bone or liver disease - primary stimulus is bile duct obstruction
GGT specific to biliary epithelium

Question 15

I want you to fill this in with tests to determine etiology, you will be so smart if know it:

Viral Hepatitis:
Autoimmune Hepatitis:
Wilson's Disease:
Alpha1A Deficiency:
Hemochromatosis:
Primary Biliary Sclerosis:

Answer 15

• Viral Hepatitis: Serology, DNA/RNA
• Autoimmune Hepatitis: ANA, anti-smooth muscle Ab
• Wilson’s Disease: Ceruloplasmin
• Alpha1A Deficiency:A1AT levels, phenotype
• Hemochromatosis: Fe, TIBC, transferrin sat., genetics
• Primary Biliary Sclerosis: AMA (anti-mito antibodies)

Question 16

Specific features on liver biopsy can sometimes determine etiology –>

Ground glass hepatocytes:
Plasma Cells (AIH):
Lymphocytic/granulomatous cholangitis:
Fibrous Obliterative cholangitis:
Perportal hepatitis with mild stensosis:
Globular Hepatocyte inclusions: A1AT deficiency:

Answer 16

Ground glass hepatocytes: Chronic Hep B
Plasma Cells (AIH): Autoimmune hepatitis or PBC
Lymphocytic/granulomatous cholangitis: PBC
Fibrous Obliterative cholangitis: PSC
Periportal hepatitis with mild stensosis: Chronic Hep C
Globular Hepatocyte inclusions: A1AT deficiency