Flashcards in EXAM #2: LIVER PATHOLOGY IV Deck (60)
What is Hereditary Hemochromatosis?
Herediatry disorder that increases the amount of iron absorbed from the gut
What gene is implicated in Hereditary Hemochromatosis?
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?
4) Skin pigmentation
What is the mnemonic to remember the causes of secondary iron overload? What is most common?
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?
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?
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
4) Hemolytic anemia
What is the most common initial manifestation of Wilson's Disease in children?
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?
How is Wilson's Disease treated?
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?
- 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?
What are the clinical manifestations of alpha-1 antitryspin deficiency in adults?
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