EXAM #2: LIVER PATHOLOGY IV Flashcards
What is Hereditary Hemochromatosis?
Herediatry disorder that increases the amount of iron absorbed from the gut
What gene is implicated in Hereditary Hemochromatosis?
HFE gene
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
What is the pathogenic change that happens in early hemochromatosis?
Fe++ deposits in periportal hepatocytes
What is the pathogenic change that happens in advanced hemochromatosis?
Fe++ deposition in:
- Kupffer cells
- Bile duct epithelium
- Fibrous septa
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
What are the complications of Hereditary Hemochromatosis?
1) DM
2) Cardiomyopathy
3) Hypogonadism
4) Skin pigmentation
5) Pseudo-gout
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
In secondary hemochromatosis, where is iron loaded?
Macrophages i.e. Kupffer cells
What is the treatment for Hemochromatosis?
Phlebotomy
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
What is the role of ceruloplasmin in the body?
Liver protein that binds copper for non-toxic circulation in the body
What is Wilson’s Disease?
Herditary disease that causes the body to retain copper
- Decreased ceruloplasmin
- Excessive copper deposition
What organs are most affected by Wilson’s Disease?
Brain
Kidneys
What gene is mutated in Wilson’s Disease?
ATP7B copper transporter
What is the result of the mutation in Wilson’s Disease?
- Impaired biliary copper excretion
- Copper cannot get to the biliary canaliculi
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
What is the most common initial manifestation of Wilson’s Disease in children?
Hepatitis
What is the most common initial manifestation of Wilson’s Disease in adults?
Neurologic/ psychiatric disease
How is Wilson’s Disease diagnosed?
- Low serum ceruloplasmin
- Increased urinary copper
- Increased hepatic copper
What PE sign is associated with Wilson’s Disease?
Kayser-Fleischer rings
How is Wilson’s Disease treated?
Chelation
What is alpha-1 antitryspin deficiency?
- Deficiency in the enzyme that inhibits proteases
- Leads to abnormal breakdown of proteins, especially in lungs
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
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?
asdf
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
