IRON Metabolism Flashcards
In post-menopausal female or male, if they have iron deficiency with no obvious cause. . .
. . you HAVE to look in the GI tract - must send to colonoscopy and not miss a GI bleed!
What is the mechanism by which anemia of chronic disease works?
- There is too much hepcidin
- Bioavailability is the issue
What is ferritin?
Your storage iron
What is the concept of heme iron and ferric iron in iron absorption (why vegetarians don’t absorb as well)?
- Dietary iron is present in two forms in the diet
- Heme iron (hemoglobin and myoglobin in beef, chicken, fish, etc.) = best absorbed [O2 binds Fe2+ better- ferrous]
- Non-heme iron/Fe3+ (cereal, vegetables) = taken up less avidly
- Greater than 1/3 of iron is from fortification of flour
Hepatocyte?
-Master regulator
Hepatocyte?
- Master regulator via its production of hepcidin
- Hepcidin is the keystone regulator of systemic iron homeostasis
What is Hepcidin?
- Master regulator of systemic iron homeostasis
- 25 AA polypeptide produced in response to inflammation (AOCD, IL6) and increased iron stores
- Binds to ferroportin and triggers its internalization and degradation to lysosomes
- Decreases Fe release from macrophages, enterocytes, and hapatocytes
- Results in increased IC iron
What does Hepcidin deficiency cause?
Iron overload
What does excess hepcidin cause?
AOCD
What happens in iron overload?
- When a lot of iron is around, transferrin saturation is high
- Hepcidin will then be generated
- Hepcidin will bind the enterocyte in the liver - this doesn’t allow for the release of iron at the enterocyte.
- No absorption occurs and no iron gets into the circulation!
What happens in the body when you have excess iron?
More hepcidin is produced!
-Hepcidin binds to duodenal enterocytes and triggers their degradation
When there is high iron, transferrin saturation is ____. When there is low iron, transferrin saturation is ___.
high, low
When transferrin saturation is low. . .
. . .the cell does not make hepcidin.
What is the primary therapy for hemochromatosis?
Hemachromatosis = too much iron and the number one way to get rid of it = REMOVING BLOOD FROM PATIENT
Increase in transferrin saturation signals to hepatocytes to increase hepcidin expression via . . .
a HFE and TfR2 dependent manner.
What is TIBC?
Total iron binding capacity - number of iron binding sites on transferrin molecules - serum transferrin concentration
What iron indices are found in iron deficiency?
Decreased Serum iron
Increased TIBC
Decreased Transferrin saturation
Decreased Ferritin
What iron indices are found in anemia of chronic disease?
Decreased Serum Iron
Decreased TIBC
Decreased Transferrin saturation
Increased Ferritin (optional)
What iron indices are found in hemochromatosis?
Increased Serum Iron
Decreased TIBC
Increased Transferrin saturation
Increased Ferratin
When you have low iron. . .
. . .body increases transferrin!
What is the mechanism by which anemia of chronic disease works?
- Increased inflammatory cytokines (IL-6, IL-1B, etc.) induce hepcidin
- There is too much hepcidin
- Bioavailability is the issue
AOCD Dx
- Chronic inflammatory process
- -Increased ESR, CRP
- -Look at other acute phase reactants (reduced albumin, transferrin)
What is the treatment for hemochromatosis?
Phlebotomy!
What is the mechanism for which HFE mutations cause hemochromatosis?
HFE is a transmembrane protein that regulated hepcidin expression.
-Mutation results in lack of interaction of HFE with TFR2 and reduced cell surface expression
