Serum Iron Metabolism and Measurement

Iron is stored in

Ferritin protein shells

The protein shell sans iron is

Apoferritin

FERRITIN

Protein shell surrounding an iron core

Found in nearly all body cells and stores iron in a form that is shielded from body fluids

Men-----800mg storage iron
Women----200 mg storage iron

If in hepatocytes/macrophages

Ferritin provides iron reserve available for hemoglobin and other heme protein synthesis

HEMOSIDERIN

Formed when ferritin is aggregated and partially de-proteinized, insoluble and found within a cell--- macrophages of the liver, spleen and BM

Iron within hemosiderin is a VERY POOR source of iron

Often present after hemorrhage

IRON METABOLISM

Dietary iron can be either stored within cells as ferritin or metabolized, which is the transfer of iron across enterocyte membrane and into the plasma

Transferrin binds to

Cell

Iron is released from

Transferrin reduced from ferric Fe3+ to ferrous Fe2+

Fe2+ is transported into

Cell via divalent metal transporter 1 (DMT1)

HEPCIDIN

key regulator of the entry of iron into the circulation, synthesized in the liver

Increased expression of hepicidin leads to

Decrease iron absorption and release

HEPCIDIN is Mainly present in

Blood in the inactive form (prohepcidin)

HEPCIDIN is Regulated by

Iron Deficiency/ Anemia & Inflammation

Hepcidin binds to

FERROPORTIN ,forms complex that is degraded in the lysosomes and iron is locked inside the cells

When Hepcidin levels are high

this lowers iron absorption in the intestine ,lowers iron releasing from hepatocytes and macrophages

Serum iron is decreased

If Hepcidin levels are low

It doesn’t bind with ferroprotin and iron can be released from enterocytes or macrophages into the circulation

Serum iron is increased

Serum Iron (Fe3+)

Measures the level of iron in the serum

TIBC (Total Iron Binding Capacity)

Measures all of the proteins in the blood that are available to bind with iron, including transferrin

Transferrin Saturation

Is a calculation that reflects the percentage of transferrin that is saturated with iron

Serum ferritin

Reflects the amount of stored iron in the body

Serum Iron

Ferric (Fe3+) iron bound to serum transferrin

Serum Iron Special Considerations

Does not include iron in hemoglobin.

Diurnal variation: highest in the morning

Serum iron concentration is decreased in

Many patients with Iron Deficiency anemia. Also acute inflammation and myocardial infarction

Elevated serum iron found in hemochromatosis, aplastic anemia, in children with

Iron poisoning, after taking an iron supplement and with acute liver injury

SERUM IRON Analysis: Chromogen-Spectrophotometric Methods

Decrease serum pH

Iron is reduced from Fe3+ to Fe2+ and complexed with a chromogen

Measure iron/chromogen complex at specific wavelength and absorbance is proportional to iron concentration

Reference intervals for serum iron differ greatly and are site specific.

LAB MEASUREMENT OF TIBC

In a normal, healthy individual, iron occupies 20- 45% of the binding sites on transferrin.

The total number of available sites capable of binding iron is measured by the TIBC.

When iron stores are low, levels of transferrin and thus TIBC increase (and vice versa)

Transferrin

Carrier protein for circulating iron

UIBC=

Unbound Iron Binding Capacity

TIBC METHODOLOGY

First: serum iron is measured

Second: Fe3+ is added in excess to saturate all
binding sites on transferrin.

Excess Fe3+ is washed away (variety of ways)

Assay for iron content is then repeated
(difference between. amount Fe3+ added & this value)=
UIBC

TIBC=

Serum Iron + UIBC

UIBC

Unsaturated Iron Binding Capacity of all iron-binding proteins in serum

Transferrin saturation (%)

100 x serum iron concentration/TIBC

Transferrin saturation in (g/L)

.007 x TIBC (ug/dL)

Transferrin saturation is Better diagnostic indicator for disease because

It establishes a relationship between iron and transferrin

In Healthy Individual

About 1/3 sites of transferrin are bound by iron

Small amount of iron in serum is

Bound to proteins other than transferrin (0.007)

Ferritin is measured by 

ELISA or Chemiluminescence assays

Ferritin Clinical Significance

Low levels: iron deficiency anemia

High levels: organ damage, inflammation, pregnancy