Iron Distribution in Human Body
The
most (about 2500 mg) of the total iron pool is contained in the erythrocytes as
hemoglobin bound active iron.
A
further 400 mg is required as active iron in myoglobin and various enzymes.
Only
a small fraction (approx. 4 mg) of the body's total iron pool is in the form of
transferrin-bound transport iron in the blood plasma.
It is thus once again clear that the
measurement of iron in plasma does not provide a true picture of the available
storage iron.
The total iron store
of the body is around 4g, mainly as hemoglobin. The daily requirement is
normally around 1mg.
Iron Storage in Human Body
Iron is stored in the form of ferritin or its
semicrystalline condensation product hemosiderin in the liver, spleen, and bone
marrow. Every cell has the ability to store an excess of iron through ferritin
synthesis.
The
transferrin-Fe3+ complex is bound to the transferrin receptor of the cell
membrane. Iron uptake can therefore be regulated by the transferrin receptor
expression. Iron directly induces the synthesis of apoferritin, the iron-free
protein shell of ferritin, on the cytoplasmic ribosomes.
In
addition to the general mechanisms of cellular iron storage and uptake, the
liver and the spleen also have specialized metabolic pathways. Hepatocytes, for
example, can convert Haptoglobin-bound or hemopexin-bound hemoglobin-Fe2+ or
Heme-Fe2+ from intravascular hemolysis or from increased heme absorption into
ferritin-Fe3+ storage in iron.
On
the other hand, the regular lysis of senescent erythrocytes and the associated
conversion of Fe2±hemoglobin into Fe3±ferritin storage iron takes place mainly
in the reticuloendothelial cells of the spleen. The reexport of Fe from storage
cells and binding to transferrin requires an intracellular oxidation by
ceruloplasmin.
|
Iron storage form |
Ferritin |
Hemosiderin |
|
Iron storage ratio |
Two thirds of the stores |
Third |
|
chemical composition |
Iron-protein complex |
------ |
|
crystal structure |
Hollow Globular Protein (apoffertin) + Crystal
center |
Partially abstracted from the apoffertin part, which
is derived from ferritin |
|
Water solubility |
Water soluble |
Water insoluble |
|
Fluctuation to hemoglobin |
Easier and faster than hemosiderin |
Harder and less than ferritin |
|
Presence |
Small amounts in plasma |
In small amounts within macrophages in the bone
marrow, liver and spleen |
|
Function |
A buffer for iron within the cytoplasm (remember
that Free iron liberates free radicals) |
------ |
|
Visibility by light microscopy in pure sections
after staining with pearlescent color |
We can’t see it |
We can see it |
|
Ferritin |
Haemoglobin |
|
A universal protein inside cells which stores and
releases iron |
Occurs in the red blood cells of all vertebrates and
tissues of invertebrates |
|
The protein responsible for the transport of oxygen
in the blood of vertebrates |
the protein responsible for the transport of oxygen
in the blood of vertebrates |
|
a globular protein comprising of 24 subunits |
A globular protein comprising of 4 subunits |
|
Subunits: Light (L) and heavy (H)type |
Subunits: Alpha, Beta, Delta and Gamma |
|
Molecular weight 474 KDa |
Molecular weight 64 kDa |
|
the major protein responsible for iron storage |
The main protein responsible for the transport of
oxygen through the blood |
|
Normal levels 30-300ng/mL for males and 18-160ng/mL |
Normal levels 13.5-17.5 g/dL for males and 12.0-15.5
g/dL for females |
|
Important to identify iron deficiency anemia |
Blood tests can reveal both anemia and
hemoglobinopathies |
Ferritin and Isoferritin
Ferritin
is a macromolecule having a molecular weight of at least440 kD (depending on
the iron content). Ferritin is a good indicator of iron stores in the body30%
of iron is stored as ferritin or hemosiderin in the phagocytic and liver
cells. The rest of 3% is lost in the
urine, sweat, feces, bile, and gut. The iron that is not lost is continuously
recycled through transferrin. Ferritin in the serum correlates with body iron
stores.
|
Storage |
Men mg (%) |
Women mg (%) |
|
Ferritin (Liver) |
1000 (29%) |
400 (16.3%) |
Ferritin
is the primary storage compound for iron, found in the liver, spleen and bone
marrow, gastrointestinal mucosa, and reticuloendothelial system. Ferritin is
the most sensitive test for iron deficiency anemia.
Ferritin
act as an acute-phase protein, so it may be elevated, which do not indicate
iron storage like:
- Acute inflammatory diseases.
- Infections.
- Metastatic cancers and lymphomas.
- Alcoholism.
- Collagen diseases.
- Uremia.
At least 20 isoferritins can be distinguished using isoelectric focusing. The microheterogeneity is due to differences in the contents of acidic H subunits and slightly basic L subunits. The basic isoferritins are responsible for long-term iron storage, and are found mainly in the liver, spleen, and bone marrow. Acidic isoferritins are found mainly in myocardium, placenta, and tumor tissue, and in smaller quantities also in the depot organs. They have lower iron contents, and presumably function as intermediaries for the transfer of iron in synthetic processes.
When
the body iron store is high, then ferritin of mucosal epithelial cells is high,
and transferrin will be low. Ferritin is present in the blood in very low
concentrations. Normally ∼ 1% of the plasma
iron is present in the form of ferritin. 40 to 80 mL of blood is lost during
the menstrual cycle, and 20 to 40 mg of iron. Plasma ferritin concentration
declines very early in the development of iron deficiency before changes in
hemoglobin appear.
Ferritin
level rises persistently in male and postmenopausal women. The decrease in the
ferritin level indicates iron storage decreases and iron deficiency anemia. Pregnancy
is associated with decreased ferritin levels.
Ferritin
level is also used in patients with chronic renal diseases to monitor the iron
stores. Increased ferritin level is a sign of excess iron seen in:
- Hemochromatosis
- Hemosiderosis
- Iron poisoning
- Recent blood transfusion
- Megaloblastic anemia
- Hemolytic anemia