Iron Metabolism - Goueli Flashcards
Iron deficiency in male or post-menopausal female. Look at?
GI tract for bleeding!
Don’t miss this!
How is iron excreted?
NO physiologic pathway for excreting excess iron!
- Absorption is highly regulated so you don’t get too much
- Obligatory losses to to sloughing of cells in intestine, GU and skin.
Major use of iron?
Making hemoglobin (Hgb)
Transferrin?
Ferritin?
Hemosiderin?
Transferrin– transfers iron in blood
Ferritin- stores iron
Hemosiderin- long term storage
Two forms of Iron:
- Heme Iron (Fe2+)
- Ferric Iron (Fe3+)
- Heme Iron (Fe2+)= best absorbed. Get from meat.
2. Ferric Iron (Fe3+) = get from veggies. This doesn’t absorb as well so sometimes worry about vegan’s iron levels.
Effect of acidic pH of stomach on iron?
Favors conversion of ferric (Fe3+) to ferrous (F2+) which is more soluble.
the better to absorbed version :)
Effect of acidic pH of stomach on iron?
Favors conversion of ferric (Fe3+) to ferrous (F2+) which is more soluble.
the better to absorbed version :)
DMT1
Transporter that brings Fe2+ iron into enterocyte
Ferroportin
ONLY iron exporter we have.
What form is needed to attach to transferrin?
Fe3+!
Haephestin converts Fe2+ –> Fe3+
Keystone regulator of systemic iron homeostasis?
Hepcidin
Works by regulating ferroportin and controlling the release of iron from macrophages, enterocytes, and hepatocytes
-Binds to ferroportin and triggers its internalization and degradation in lysosomes.
When is hepcidin produced?
In response to inflammation and increased iron stores.
Excess hepcidin?
Anemia of Chronic Disease (AOCD)
Hepcidin deficiency?
Iron Overload
Hepcidin deficiency?
Iron Overload
Pathway to hepcidin production?
- Inflammation
- cytokines –> activats JAK/STAT
- Transcription of HAMP gene
OR
- High transferrin saturation
- HFE/TFR2 activate
- increase HAMP gene expression to make more hepcidin
Indirect indicators of Fe status
- serum iron concentration
- TIBC
- Transferrin saturation
- Serum ferritin
Iron Deficiency Anemia:
Reticulocytes are NOT increased
Serum Test:
-reduced Fe, Tf Sat, Ferritin (makes sense- you don’t have much iron so you won’t be storing it and Tf wont get saturated)
Increased: TIBC, transferrin, transferrin receptors (b/c you want to increase the ability to transport the Fe that you have)
Anemia of Chronic Disease (AOCD)
- Hypoproliferative anemia secondary to inflammation
- Iron stores increased, but decreased iron utilization (unavailable)
- IL’s induce hepcidin
AOCD serum levels:
Low: serum iron, TIBC
Normal to elevated ferritin concentration
Normal transferrin receptors
AOCD serum levels:
Low: serum iron, TIBC
Normal to elevated ferritin concentration
Normal transferrin receptors
AOCD: MOA
Hepcytin binds ferroportin so iron can’t get out of cell.
Mechanism of hemochromatosis:
Autosomal Recessive
-Cysteine to tyrosine sub at amino acid 282 (C282Y) == HFE gene mutation
Normally HFE interacts w/ TFR1/2 to regulate hepcidin expression.
HFE gene mutation –>
Decreased hepcidin expression
- increased Fe absorption
- increased serum iron and Tf Sat
- decreased storage of iron in macs
Triad of hemochromatosis
- DM
- Hepatomegaly
- Hyperpigmentation
Hemochromatosis serum levels
Elevated: serum iron, ferritin, Tf Sat (>45%)
Decreased: TIBC, Transferrin
Therapies for hemochromatosis:
PHLEBOTOMY
