Hemochromatosis Flashcards
Types of hemochromatosis?
Primary or acquired
Secondary (aka Hemosiderosis)
Hereditary hemochromatosis (HH) is autosomal ___________ (reccessive/dominant) disease
autosomal reccessive
The mutation is on the short arm of chromosome ___ and ass. w/ HLA A3 in HH
6
HH is more common in _________ (males/females)
males
HH is diagnosed 10-20 years after menopause but it is diagnosed earlier in males. Why?
Females have a way of losing extra iron through menses.
What is the pathogenesis of HH?
Increased iron absorption → Increased serum iron
Excess iron gets deposited in tissues
Excess iron makes free radicals that causes 3 things
1. Lipid peroxidation
2. Fibrosis
3. DNA damage causing HCC
Fibrosis occurs when iron in the liver is around or more than ________ ug
22000
What is the classic tetrad in HH?
Cirrhosis
Abnormal skin pigmentation
Diabetes mellitus
Restrictive cardiomyopathy
Classic tetrad is usually seen _________ (early/late) in HH
late
Symptoms develop when iron is more than ____ gm in the body
20
What r the clinical findings in HH
Cirrhosis, Hepatomegaly Diabetes mellitus Malabsorption Restrictive CM and arrhythmias Hypogonadism Acute synovitis and pseudogout, DJD Slate gray color of skin
What is bronze diabetes?
Hemochromatosis is sometimes referred to as bronze diabetes because it can lead to darkening of the skin and hyperglycemia
MCC of death in HH is _______
HCC
What will be the results of iron profile? Iron Ferritin Transferrin TIBC Transferrin iron saturation
Iron ↑ Ferritin ↑ Transferrin ↓ TIBC ↓ Transferrin iron saturation ↑
What will be other lab findings other than iron profile?
Hyperglycemia
↓ LH and ↓FSH
What is used more nowadays for dx of HH?
Liver biopsy OR HFA gene testing
HFA gene testing
Serum _______ levels are also used to follow therapy in HH.
ferritin
What are the genes involved in HH?
HAMP - makes hepcidin
Hemojuvelin HJV
HFE
TFR2
Transcription of hepcidin is increased by two things.
Iron
Inflammatory cytokines
Transcription of hepcidin is decreased by 3 things.
Iron deficiency
Hypoxia
Ineffective erythropoiesis
Which form of HH is milder? Adult or Juvenile
Adult
Mutations ass. w/ adult form of HH
HFE
C282Y (europeans) and H63D (worldwide)
Juvenile form of HH is severe and involves _______ and _______ mutations
HAMP
HJV
What happens to the liver in HH (early and late stages)
Early - large chocolate brown w/ yellow brown hemosiderin globules
Late - dark brown to black, shrunken and micronodular cirrhosis
