EXAM #2: LIVER PATHOLOGY IV

Question 1

What is Hereditary Hemochromatosis?

Answer 1

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

Question 2

What gene is implicated in Hereditary Hemochromatosis?

Answer 2

HFE gene

Question 3

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

Answer 3

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

Question 4

What is the pathogenic change that happens in early hemochromatosis?

Answer 4

Fe++ deposits in periportal hepatocytes

Question 5

What is the pathogenic change that happens in advanced hemochromatosis?

Answer 5

Fe++ deposition in:

• Kupffer cells
• Bile duct epithelium
• Fibrous septa

Question 6

What are the lab findings in Hereditary Hemochromatisis?

Answer 6

• High Ferretin
• Low TBIC
• High serum iron
• High % saturation

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

Question 7

What are the complications of Hereditary Hemochromatosis?

Answer 7

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

Question 8

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

Answer 8

THALAS

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

Question 9

In secondary hemochromatosis, where is iron loaded?

Answer 9

Macrophages i.e. Kupffer cells

Question 10

What is the treatment for Hemochromatosis?

Answer 10

Phlebotomy

Question 11

List the roles that copper plays in the body.

Answer 11

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

Question 12

What is the role of ceruloplasmin in the body?

Answer 12

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

Question 13

What is Wilson’s Disease?

Answer 13

Herditary disease that causes the body to retain copper

• Decreased ceruloplasmin
• Excessive copper deposition

Question 14

What organs are most affected by Wilson’s Disease?

Answer 14

Brain

Kidneys

Question 15

What gene is mutated in Wilson’s Disease?

Answer 15

ATP7B copper transporter

Question 16

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

Answer 16

• Impaired biliary copper excretion

- Copper cannot get to the biliary canaliculi

Question 17

What are the clinical manifestations of Wilson’s Disease?

Answer 17

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

Question 18

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

Answer 18

Hepatitis

Question 19

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

Answer 19

Neurologic/ psychiatric disease

Question 20

How is Wilson’s Disease diagnosed?

Answer 20

• Low serum ceruloplasmin
• Increased urinary copper
• Increased hepatic copper

Question 21

What PE sign is associated with Wilson’s Disease?

Answer 21

Kayser-Fleischer rings

Question 22

How is Wilson’s Disease treated?

Answer 22

Chelation

Question 23

What is alpha-1 antitryspin deficiency?

Answer 23

• Deficiency in the enzyme that inhibits proteases

- Leads to abnormal breakdown of proteins, especially in lungs

Question 24

What genotype is assocaited with alpha-1 antitrypsin?

Answer 24

PiZZ

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

Question 25

What is the etiology of alpha-1 antitryspin deficiency?

Answer 25

Misfolded/nonfunctional PiZ accumulates in hepatocytes

Question 26

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

Answer 26

Hepatitis/cholestasis

Question 27

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

Answer 27

Chronic hepatitis/cirrhosis

Question 28

How is alpha-1 antitryspin deficiency diagnosed?

Answer 28

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

Question 29

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

Answer 29

Early onset emphysema

Question 30

What is Focal Nodular Hyperplasia of the liver?

Answer 30

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

Question 31

What is the morphological appearance of Focal Nodular Hyperplasia?

Answer 31

Solitary mass on the liver with a central scar

Question 32

What is Nodular Regenerative Hyperplasia?

Answer 32

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

Question 33

What is Nodular Regenerative Hyperplasia commonly confused with?

Answer 33

Cirrhosis

Question 34

What is the most common complication of Nodular Regenerative Hyperplasia?

Answer 34

Noncirrhotic portal hypertension

Question 35

What is the surgical treatment for Nodular Regenerative Hyperplasia?

Answer 35

Transjugular Intrahepatic Portal Shunt

Question 36

What is Nodular Regenerative Hyperplasia associated with?

Answer 36

Transplantation Chemotherapy Vasculitis

Question 37

What is the most common benign hepatic tumor?

Answer 37

Hemangioma

Question 38

What is a Hemangioma?

Answer 38

Blood vessel tumor

Question 39

What patient population are Hemangiomas more common in?

Answer 39

Women on oral contraceptives

Question 40

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

Answer 40

Do NOT biopsy

Question 41

What is a Liver Cell Adenoma?

Answer 41

Glandular tumor of the liver

Question 42

What patient populations are Liver Cell Adenomas more common in?

Answer 42

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

Question 43

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

Answer 43

Rupture during pregnancy

Question 44

What is the most common primary malignant liver tumor?

Answer 44

Hepatocellular Carcinoma

Question 45

Geographically, where is HCC most common?

Answer 45

Asia | Africa

Question 46

What is the biggest risk factor for HCC?

Answer 46

Cirrhosis and the other disorders that lead to cirrhosis

Question 47

List the risk factors for HCC.

Answer 47

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

Question 48

What genetic change is associated with progression to HCC?

Answer 48

p53 Note that Aspergillus/ aflatoxin causes p53 mutations

Question 49

How does HBV lead to HCC?

Answer 49

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

Question 50

What are the clinical manifestations of HCC?

Answer 50

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

Question 51

What lab elevation is associated with HCC?

Answer 51

AFP greater than 1,000

Question 52

What subtype of HCC has the best prognosis?

Answer 52

Fibrolamellar HCC

Question 53

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

Answer 53

Cholangiocarcinoma

Question 54

What are the risk factors for Cholangiocarcinoma?

Answer 54

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

Question 55

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

Answer 55

Hepatoblastoma

Question 56

What is a Hepatoblastoma?

Answer 56

asdf

Question 57

What lab is associated with Hepatoblastoma?

Answer 57

Elevated AFP

Question 58

What is an angiosarcoma?

Answer 58

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

Question 59

What is the most common malignant tumor of the liver?

Answer 59

Metastases

Question 60

Where are the primary tumors of liver metastases commonly located?

Answer 60

- GI - Breast - Lung - Pancreas - Melanoma