Hereditary Haemochromatosis Flashcards
Which transporters absorb iron, where are they located?
Duodenal enterocytes
Divalent metal transporters absorb iron
Which transporters export iron to the blood?
Ferroportin
How is iron transporter, how is it stored?
Transferrin
Ferritin
What is an important regulator of iron absorption?
Hepcidin - is produced by the liver and inhibits ferroportin
it is increased when there is excess iron or inflammation
How is iron excreted?
1-2mg of iron is shed in the sloughed epithelial cells
What are the regulators of hepcidin release?
There are multiple factors needed for synthesis and release of hepcidin, iron stimulates its production
It is part of an iron sensing complex
How does iron damage occur?
It leads to saturation of transferring binding capacity and circulates as non bound free iron
The iron complexes deposit in organs and promotes free-radical generation
What is HFE?
High iron gene
It encodes protein which stimulate hepciding release
What are the types of haemochromatosis?
Type 1: HFE hemochromatosis
Type 2: Juvenile Haemochromatosis
Type 3: Transferring recetor mutation
type 4: Ferroportin mutations
What is the mechanism of type 1 haemochromatosis?
Reduced HFE, reduced hepcidin release, increased ferroportin
Is due to C282Y mutation
It causes 90% of N. European cases and present in 40-60s
What is juvenile haemochromatisis?
Haemochromatosis presenting in teenagers
What is Type 3?
Transferring receptor mutations presents in 30s
Type 4?
Ferroportin mutation
4a. ferroportin is defective so iron accumulates in macrophages
4B. ferroportin resistanct to hepcidin, iron efflux occurs leading to lots of iron deposits
What are the clinical effects of iron overload?
Hormonal: Pituitary - impaired growth and fertility Thyroid - Hypothyroidism Pancreas - diabetes Gonads - Hypogonadism
Heart - arrhythmia, cardiomyopathy and cardiac failure
Liver - cirrhosis, hepatocellular
Skin - bronzed/grey complexion
How is iron overload managed?
Phlebotomy
