Iron is an essential trace element being required for oxygen transport (as haemoglobin), redox reactions and DNA synthesis. Its metabolism is controlled by dietary absorption. Only around 10 to 20% of iron is absorbed and bioavailability is affected by various dietary constituents, for example, bioavailability is increased with meat and fruit juice and decreased by tea, nuts and milk.
There is a 10 to 20% diurnal variation of serum iron concentrations; fasting concentrations are usually lower. The iron pool in plasma changes quickly – around every 40 to 50 minutes as iron is transported mainly from the reticulo-endothelial system (where components of old red cells are recycled) to marrow. There are also large day-to-day variations of around 15%.
Transferrin is the main circulatory iron protein and the main storage protein is ferritin. Serum iron falls significantly following a systemic inflammatory response (see Table).
Chronic iron accumulation in diseases such as haemochromatosis or thalassaemia can be confirmed by direct measurement of iron in a liver biopsy or by carrying out a Desferal (desferrioxamine) test. This involves giving the patient an intramuscular injection of the chelating agent, Desferal, and collecting the urine excreted over the following six hours. Iron is normally excreted via the faecal route and urinary iron concentrations are low (about 0.5 µmol/L): following Desferal injection, urine iron normally increases by up to 18 µmol/L, whereas in patients with a storage abnormality, urine iron increases to over 50 µmol/L.
The hepatic iron index (liver iron concentration in µmol/g divided by the patient's age in years) was proposed by Bassett et al36 to differentiate genetic haemochromatosis from alcoholic siderosis, both of which result in increased liver iron concentrations. This index exceeds 1.9 in haemochromatosis but not in heterozygotes or alcoholic liver disease. The index has been evaluated in several centres and shown to be a useful diagnostic tool.
Recommended Daily Allowance
Adults: 10 to 15 mg/day.
Effect of Systemic Inflammatory Response on Serum Iron Concentrations
Table: Distribution in percentiles of serum iron concentrations according to increments of CRP concentrations (n = 16517).
|CRP (mg / L)||n (%)||
Median serum iron concentration
|≤ 3||3722 (23 %)||14|
|3 - 5||1428 (9 %)||13||NS|
|5 - 10||2154 (13 %)||11||<0.001|
|10 - 20||2132 (13 %)||9||<0.001|
|20 - 40||2167 (13 %)||7||<0.001|
|40 - 80||2166 (13 %)||5||<0.001|
|> 80||2748 (17 %)||3||<0.001|
Sample Requirements and Reference Ranges for Iron
|Sample Type||Urine (timed or 24 h collection), liver|
|Container||Urine & liver: universal container|
Urine: Please mix 24 hour urine well before taking an aliquot.
Urine: 1 mL* of a 24 h collection
Liver biopsy: 0.5 mg (results are an approximation if biopsy weight <1 mg)
Urine: < 1 µmol/L37
Liver: 0.17-1.40 mg/g dry weight30
Hepatic Iron Index: 0 to 2 µmol iron/gram liver/year36
|Mean turnaround time||Urine: 4.5 days|
|Method||Inductively Coupled Plasma Mass Spectrometry|
Urine: Traceable to reference material produced in accordance with EN ISO 17511:2003 “In vitro diagnostic medical devices. Measurement of quantities in biological samples. Metrological traceability of values assigned to calibrators and control materials” and reference materials with values determined by reference laboratories.
Liver: Traceable to certified reference material BCR 185R and ERM – BB186.
|Intermediate Precision (CV)||
Urine: 9.2% at 0.62 µmol/L, 3.7% at 3.31 µmol/L
Liver: 6.4% at 0.21 mg/g, 6.7% at 0.29 mg/g
|Measurement Uncertainty, U||
Urine: 0.7 ± 0.15 µmol/L, 3.7 ± 0.25 µmol/L
Liver: 0.2 ± 0.04 mg/g, 0.3 ± 0.04 mg/g
|Analytical Goals (CV)||Urine: 10%**, Liver: 7%**|
|EQA Scheme||Urine and liver: UK NEQAS, Guildford (Urine - once per month; liver - four times per year).|
* Absolute minimum volume; this volume is insufficient to carry out repeat analysis if analysis fails.
** Goal Origin: STEMDRL state-of-the-art