Iron kinetics Flashcards
% of inorganic Iron is absorbed
10%
Entry of non-heme iron?
- DcytB (Duodenal cytochrome B): Ferroreductase
2. DMT1 (Divalent Metal Transporter)
Entry of heme iron
HCP1
Where is iron absorbed?
Enterocyte
Epithelial cells
What protein converts Ferrous to Ferric for transport in blood?
Hephaestin
What type of iron can be transported in blood?
Ferric (Fe3+)
What cells store/transport Iron?
Enterocytes
Hepatocytes
Macrophages
How much iron is derived from RBC turnover?
20-25mg/day
Form of stored Iron?
Ferritin
The transporter of iron across cell membrane
Ferroportin
What cells have Transferrin receptor (TfR)?
All cells except RBC
How many Iron per transferrin? and what type of Iron?
2 Ferric molecules are transported per transferrin.
Mechanism of Iron transport through TfR?
- TfR bind Tf and prompt endocytosis
- pH drops (acidification) and Iron released.
- TfR is recycled to the cell surface
What cells have ferritin the most?
Liver
Bone Marrow
Spleen
Reticuloendothelia Macrophage
Role of Hepcidin
Degrade ferroportin
no more exported Iron
What regulate Hepcidin
Transferrin
What type of Iron can be exported through the cell membrane?
Ferrous (Fe2+)
Iron distribution in adults
2-3g/female
4g/male
Iron daily requirements
1mg for men and postmenopausal women
1.5mg for women in reproductive years
2-3mg for pregnant and lactating women
How much iron is drained by menstrual cycle annually?
20-40mg
What is SI?
Serum Iron = Iron bound to Transferrin
What is TIBC
Total Iron Binding Capacity
All the binding site available on transferrin.
What reagent is used to wash the excess Fe3+ in TIBC test?
MgCO3
How to calculate the % transferrin saturation
SI/TIBC * 100
What is Transferrin?
Plasma protein carrying iron (Fe3+) to developing Erythroid cells.
When is Serum Ferritin elevated?
By the Acute Phase Response:
- Produced by liver during inflammation
- Sequester by Bacteria
What is hemosiderin
Contains hundreds of ferritin as an insoluble complex.
Lost some surface proteins
What are difference between Hemosiderin ans Ferritin?
- Surface proteins
Degraded in Hemosiderin - Iron concentration
Higher in Hemosiderin - Release Iron
Faster in Ferritin
When is Purissan Blue used?
To test stored iron by staining hemosiderin (NOT ferritin)
Zinc Protoporphyrin Assay
Detect when Heme syn is inhibited due to the lack of Iron (Zn binds Protoporphyrin IX instead Fe)
How is ZPP assay reported?
The assay is reported as Free Erythrocyte Protoporphyrin
OR: ZPP/Heme
The elevation of sTfR indicates?
Cells produce more TfR when stored iron is low. The TfR is shed become sTfR in plasma.
The elevation of sTfR indicates the low level of stored iron
Percentage of Iron in body
70% in Hgb
15-30% in liver and RE
4% Myoglobin
0.1% in plasma transferrin
Total body Iron
3-5 g
1-2mg in flux
Stage 1 of Iron Deficiency
Low Iron storage. Hematopoiesis is not affected
Stage 2 of Iron Deficiency
Storage Iron is very low
Hematopoiesis is depend of transported Iron
Lab test of IDA
Low SI Low ferritin Incre TIBC Decre % Tf sat. Low sTfR
Stage 3 of Iron Deficiency
Depletion of stored and transport Iron
Dietary allowance for Iron
14-18 yrs:
19-50 yrs:
14-18 yrs: 11-15mg
19-50 yrs: 8/m - 18/f
IDA Oral treatment
325mg FeSO4 (1-3 tablets/day) = 30-60 mg
Disadvantage of Oral treatment
GI side effect
Slow (4-6 weeks)
Fail during treatment
IDA Parental treatment
4 units of RBC (1000mg IV) -> Hgb points increase 4.
Where is Lactoferrin
In Neutrophils
Lab test for Anemia of Chronic Inflammation
Low SI
Decr TIBC
Normal or low % saturated Tf
High serum Ferritin
Sideroblastic Anemia
Deficiency protoporphyrin synthesis
How is BM in Sideroblast Anemia
Abundant of Iron
Iron in Normoblast waiting for Heme syns.
Enzyme is affected in CEP
Uroporphyrinogen Synthase III
Enzyme is affected in EPP
Ferrochelatase
Congenital Erythropoietic Porphyria
Autosomal Recessive
Erythropoietic Protoporphyria
Autosomal Dominant
How lead interferes Heme synthesis?
Block ALA to PBG
Block Fe bind to Protoporphyrin IX
Lab test for Sideroblastic Anemia
High Iron in BM High SI High % transferrin saturation Normal TIBC High serum Ferritin
Overload Iron
Hemochromatosis
What gene get mutated in Hemochromatosis?
HFE gene
- Lack of Hepcidin
- Constitutive absorption of Iron
- Absorb 4mg Iron daily
Lab test of Hemochromatosis
High SI
High % Tf sat.
Low TIBC
High serum Ferritin
