EXAM #2: LIVER PATHOLOGY IV Flashcards by Jonathan Kallevang

What is Hereditary Hemochromatosis?

Herediatry disorder that increases the amount of iron absorbed from the gut

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What gene is implicated in Hereditary Hemochromatosis?

HFE gene

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What is the link between transferrin, hepcidin, and iron absorption?

Hepcidin blocks Fe++ absorption from the gut
Decreased Hepcidin causes increased Fe++ absorption from the gut
HFE membrane product regulates the transcription of Hepcidin

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What is the pathogenic change that happens in early hemochromatosis?

Fe++ deposits in periportal hepatocytes

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What is the pathogenic change that happens in advanced hemochromatosis?

Fe++ deposition in:

Kupffer cells
Bile duct epithelium
Fibrous septa

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What are the lab findings in Hereditary Hemochromatisis?

High Ferretin
Low TBIC
High serum iron
High % saturation

*Classically there is 2x normal transferrin saturation and and drastically elevated serum ferretin

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What are the complications of Hereditary Hemochromatosis?

1) DM
2) Cardiomyopathy
3) Hypogonadism
4) Skin pigmentation
5) Pseudo-gout

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What is the mnemonic to remember the causes of secondary iron overload? What is most common?

THALAS

T= Transfusion***** 
H= Hemochromatosis 
A= Alimentary (Bantu siderosis)
L= Liver Disease 
A= Anemia (Thalassemia) 
S= Sideroblastic anemia

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In secondary hemochromatosis, where is iron loaded?

Macrophages i.e. Kupffer cells

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What is the treatment for Hemochromatosis?

Phlebotomy

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List the roles that copper plays in the body.

1) Pigment formation
2) NT production
3) Peptide formation
4) Connective tissue biosynthesis
5) Antioxidant defense

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What is the role of ceruloplasmin in the body?

Liver protein that binds copper for non-toxic circulation in the body

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What is Wilson’s Disease?

Herditary disease that causes the body to retain copper

Decreased ceruloplasmin
Excessive copper deposition

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What organs are most affected by Wilson’s Disease?

Brain

Kidneys

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What gene is mutated in Wilson’s Disease?

ATP7B copper transporter

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What is the result of the mutation in Wilson’s Disease?

Impaired biliary copper excretion

- Copper cannot get to the biliary canaliculi

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What are the clinical manifestations of Wilson’s Disease?

1) Degeneration of the basal ganglia causing a PD like pheotype
2) Hepatitis
3) Cirrhosis
4) Hemolytic anemia
5) Cardiomyopathy

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What is the most common initial manifestation of Wilson’s Disease in children?

Hepatitis

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What is the most common initial manifestation of Wilson’s Disease in adults?

Neurologic/ psychiatric disease

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How is Wilson’s Disease diagnosed?

Low serum ceruloplasmin
Increased urinary copper
Increased hepatic copper

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What PE sign is associated with Wilson’s Disease?

Kayser-Fleischer rings

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How is Wilson’s Disease treated?

Chelation

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What is alpha-1 antitryspin deficiency?

Deficiency in the enzyme that inhibits proteases

- Leads to abnormal breakdown of proteins, especially in lungs

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What genotype is assocaited with alpha-1 antitrypsin?

PiZZ

Normal genotype of antitrypsin is PiMM
PiZZ variant is the most clinically significant form that leads to alpha-1 antitrypsin deficiency

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What is the etiology of alpha-1 antitryspin deficiency?

Misfolded/nonfunctional PiZ accumulates in hepatocytes

What are the clinical manifestations of alpha-1 antitryspin deficiency in children?

Hepatitis/cholestasis

What are the clinical manifestations of alpha-1 antitryspin deficiency in adults?

Chronic hepatitis/cirrhosis

How is alpha-1 antitryspin deficiency diagnosed?

- Low serum Alpha-1 AT - Abnormal Alpha-1 AT electrophoresis - Liver biopsy

Aside from liver disease, what else is highly associated with alpha-1 antitryspin deficiency?

Early onset emphysema

What is Focal Nodular Hyperplasia of the liver?

- Benign tumor of the liver - More common in women - Asymptomatic--does NOT require treatment

What is the morphological appearance of Focal Nodular Hyperplasia?

Solitary mass on the liver with a central scar

What is Nodular Regenerative Hyperplasia?

Diffuse nodular transformation of the liver WITHOUT fibrosis ****Think of regeneration gone awry*****

What is Nodular Regenerative Hyperplasia commonly confused with?

Cirrhosis

What is the most common complication of Nodular Regenerative Hyperplasia?

Noncirrhotic portal hypertension

What is the surgical treatment for Nodular Regenerative Hyperplasia?

Transjugular Intrahepatic Portal Shunt

What is Nodular Regenerative Hyperplasia associated with?

Transplantation Chemotherapy Vasculitis

What is the most common benign hepatic tumor?

Hemangioma

What is a Hemangioma?

Blood vessel tumor

What patient population are Hemangiomas more common in?

Women on oral contraceptives

What do you need to remember about the diagnosis of a Hemangioma?

Do NOT biopsy

What is a Liver Cell Adenoma?

Glandular tumor of the liver

What patient populations are Liver Cell Adenomas more common in?

- Young women on oral contraceptives | - GSD (I and III)

What is the most feared complication of a Liver Cell Adenoma?

Rupture during pregnancy

What is the most common primary malignant liver tumor?

Hepatocellular Carcinoma

Geographically, where is HCC most common?

Asia | Africa

What is the biggest risk factor for HCC?

Cirrhosis and the other disorders that lead to cirrhosis

List the risk factors for HCC.

1) Chronic hepatitis (HBV and HCV) 2) Cirrhosis - Alcohol - NAFLD - Hemochromatosis - Wilson's - A1AT 3) Aflatoxin

What genetic change is associated with progression to HCC?

p53 Note that Aspergillus/ aflatoxin causes p53 mutations

How does HBV lead to HCC?

- HBV is dsDNA virus - Integrates into host - Activates proto-oncogenes

What are the clinical manifestations of HCC?

1) Painful hepatomegaly 2) Abdominal mass 3) Weight loss 4) Portal/hepatic vein thrombosis 5) Hemorrhagic ascites 6) Hepatic Failure 7) Massive bleeding

What lab elevation is associated with HCC?

AFP greater than 1,000

What subtype of HCC has the best prognosis?

Fibrolamellar HCC

What is the primary malignant tumor of the bile duct epithelium?

Cholangiocarcinoma

What are the risk factors for Cholangiocarcinoma?

1) Primary Sclerosing Cholangitis 2) Thorotrast 3) Caroli Disease 4) Liver Flukes

What is the most common primary malignant hepatic tumor in children?

Hepatoblastoma

What is a Hepatoblastoma?

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What lab is associated with Hepatoblastoma?

Elevated AFP

What is an angiosarcoma?

This is a cancer of the inner lining of blood vessels associated with: - Thorotrast - Steroids *V. poor prognosis

What is the most common malignant tumor of the liver?

Metastases

Where are the primary tumors of liver metastases commonly located?

- GI - Breast - Lung - Pancreas - Melanoma