HHC/Wilson/A1AT Flashcards
AR hereditary liver disorder; body absorbs too much iron, which is then stored in the liver, skin, heart and pancreas; tissues with iron deposits take a red-orange hue; can result in fibrosis and cirrhosis; mutation in HFE gene (C282Y major, H63D minor)
Hereditary Hemochromatosis
Mutations in Hereditary Hemochromatosis
On HFE gene: C282Y (major) and H63D (minor)
(males/females) with hereditary Hemochromatosis usually present later in life with symptoms
Women: partially compensate with menstrual blood loss
On MRI abdominal imaging, what can clue you in to Hemochromatosis
Very dark liver, heart and pancreas (iron deposits)
Spleen in lighter (no deposits)
Histologic characteristics of Hemochromatosis
Periportal hepatocytes containing yellow-brown pigments (iron)
Why might hepatocellular carcinoma in the setting of hereditary hemochromatosis NOT have iron accumulation in it’s cells
Hereditary Hemochromatosis is a life-long accumulation of iron (blue), but hepatocellular carcinoma (tumor cells) is not present long enough to accumulate iron.
non-genetic mechanism for iron overload; usually seen with patients on chronic transfusion regimens (sickle cell disease, thalassemia, etc.)
Transfusion-associated iron overload
In Hemochromatosis, iron deposits begin in _____________ cells and progress to hepatocytes
Kupffer (macrophages)
Primary hemochromatosis
Transfusion Associated Iron Overload
Iron-induced reactive oxygen species
Stain used to help diagnose Hemochromatosis (iron overload)
Prussian Blue stain
How to treat/manage Hemochromatosis
Frequent phlebotomy Fe chelation (SC anemia)
How to diagnose Hemochromatosis
- Elevated transferrin/ferritin
- Genetic testing (Hereditary Hemochromatosis)
- Liver biopsy
Signs/symptoms of Hemochromatosis (Hereditary or Transfusion)
Liver: Cirrhosis and HCC Pancreas: Diabetes (damaged islet cells) Reprod: Hypogonadism Joints: Arthropathy Skin: "Bronzing" Heart: Cardiomyopathy
AR genetic disorder of copper metabolism (unable to excrete in bile); accumulation in periportal hepatocytes, kidneys, brain, joints and cornea; can lead to hepatitis, liver failure and cirrhosis; mutation in ATP7B
Wilson’s Disease
Mutation seen in Wilson’s Disease (copper retention)
ATP7B
Normally, copper is excreted by the liver in the….
bile
Patients with Wilson disease have low…
ceruloplasmin (protein that carries copper in blood) (less of it means more is stored in tissues and not excreted)
Signs/Symptoms of Wilson’s Disease (copper retention)
Liver: hepatitis, cirrhosis and failure
Heme: hemolytic anemia
Neuro: psychosis, seizures, ataxia, tremors, behavior changes
Renal: proximal RTA, nephrolithiasis
Eyes: Kayser-Fleischer Rings (golden deposits around pupil)
golden-brown deposits around pupil; seen in Wilson’s Disease (copper retention)
Kayser-Fleischer Rings
How to diagnose Wilson’s Disease
High serum/urine copper (can’t excrete in bile)
Low serum ceruloplasmin
LOW alkaline phosphatase with HIGH total bilirubin
If you see LOW alkaline phosphatase in the setting of HIGH total bilirubin, which liver disease should you think of?
Wilson’s Disease (copper retention)
How to treat/manage Wilson’s Disease (copper retention)
Chelation (zinc, Trientine, etc.) Liver transplant (for failure or cirrhosis)
genetic metabolic disorder of the lungs and liver; mutation in SERPINA1 gene and A1AT protein (serine protease inhibitor); failure to secrete A1AT, causing an accumulation and polymerization in hepatocytes; causes lung disease due to less circulating A1AT
Alpha-1-Antitrypsin Deficiency
Gene mutation associated with Alpha-1-Antitrypsin Deficiency
SERPINA1 gene
