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Heme.svg|
Iron deficiency
ICD-10 E611
ICD-9 280.9
OMIM [1]
DiseasesDB 6947
MedlinePlus 000584
eMedicine med/1188
MeSH {{{MeshNumber}}}

For a more specific and detailed discussion of anemia caused by iron deficiency, see the Wikipedia article iron deficiency anemia.

Iron deficiency (sideropenia or hypoferremia) is the most common known form of nutritional deficiency. In the human body, iron is present in all cells and has several vital functions—as a carrier of oxygen to the tissues from the lungs in the form of hemoglobin, as a transport medium for electrons within the cells in the form of cytochromes, and as an integral part of enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and mortality.

The direct consequence of iron deficiency is iron deficiency anemia. Groups that are most prone to developing this disease are children and pre-menopausal women.

Total body iron averages approximately 3.8 g in men and 2.3 g in women. In blood plasma, iron is carried tightly bound to the protein transferrin. Bacteria, like human cells, require iron for growth, and restricting its bioavailability in this way prevents their infectious growth. Indeed, during fever, one way of controlling bacteria growth is through temporary hypoferremia.

There are several mechanisms that control human iron metabolism and safeguard against iron deficiency. The main regulatory mechanism is situated in the gastrointestinal tract. When loss of iron is not sufficiently compensated by adequate intake after some time that is determined by the state of body iron storage, iron deficiency develops.

Causes

  • chronic bleeding (hemoglobin contains iron)
  • inadequate intake (special diets low in dietary iron)
  • substances (in diet or drugs) interfering with iron absorption
  • malabsorption syndromes
  • fever where it is adaptive to control bacterial infection

Though genetic defects causing iron deficiency have been studied in rodents, there are no known genetic disorders of human iron metabolism that directly cause iron deficiency.

Symptoms

Symptoms of iron deficiency can occur even before the condition has progressed to iron deficiency anaemia.

Symptoms of iron deficiency are not unique to iron deficiency (ie not pathognomonic). Iron is needed for many enzymes to function normally, so a wide range of symptoms may eventually emerge, either as the secondary result of the anemia, or as other primary results of iron deficiency. Symptoms of iron deficiency include:

Likely lab test results in people with iron deficiency

  • A full blood count would likely reveal microcytic anemia [2]
  • Low serum ferritin
  • Low serum iron
  • High TIBC (total iron binding capacity)
  • It is possible that the fecal occult blood test might be positive, if iron deficiency is the result of gastrointestinal bleeding.

As always, laboratory values have to be interpreted with the lab's reference values in mind and considering all aspects of the individual clinical situation.

Serum ferritin can be elevated in inflammatory conditions and so a normal serum ferritin may not always exclude iron deficiency.

Consequences

Continued iron deficiency may progress to anemia and worsening fatigue. Thrombocytosis, or an elevated platelet count, can also result. A lack of iron in the blood is a reason that some people cannot donate blood.

Treatment

Before any treatment is commenced there should be definitive diagnosis of the underlying cause for iron deficiency, particularly in older patients who are most susceptible to colorectal cancer and the gastrointestinal bleeding it often causes. In adults, 60% of patients with iron deficiency anemia may have underlying gastrointestinal disorders leading to chronic blood loss.[3] It is likely that the cause of the iron deficiency will need treatment as well.

When iron deficiency has been diagnosed the condition can be treated with iron supplements, e.g. in the form of ferrous sulfate, ferrous gluconate, or amino acid chelate tablets. Recent research suggests the replacement dose of iron, at least in the elderly with iron deficiency, may be as little as 15 mg per day of elemental iron.[4]

Food sources of Iron

Iron deficiency can have serious health consequences that diet may not be able to quickly correct, and iron supplementation is often necessary if the iron deficiency has become symptomatic. However, mild iron deficiency can be corrected, and prevented, by eating iron-rich foods. Because iron is an absolute requirement for most of the Earth's plants and animals, a wide range of food can provide iron. However, these foods are absorbed and processed differently by the body; for instance, iron from meat (heme iron source) is more easily broken down and absorbed than iron in grains ("non-heme" iron source), and minerals and chemicals in one type of food may inhibit absorption of iron from another type of food eaten at the same time.[2] For example, oxalates and phytic acid form insoluble complexes which bind iron in the gut before it can be absorbed.

Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, vegetarians and vegans should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry.[3] Legumes and dark-green leafy vegetables like broccoli, kale and oriental greens are especially good sources of iron for vegetarians and vegans. However, spinach and Swiss chard contain oxalates which bind iron making it almost entirely unavailable for absorption. Iron from nonheme sources is more readily absorbed if consumed with foods that contain either heme-bound iron or vitamin C. This is due to a hypothesised "meat factor" which enhances iron absorption. [4]

Bioavailability and bacterial infection

Iron is needed for bacterial growth making its bioavailability an important factor in controlling infection.[5] Blood plasma as a result carries iron tightly bound to transferrin, and only releases it to cells with appropriate cell markers thus preventing its access to bacteria.[6]Between 15 and 20 percent of the protein content in human milk consists of lactoferrin[7] that binds iron. As a comparison, in cow's milk, this is only 2 percent. As a result, breast fed babies have fewer infections [8] Lactoferrin is also concentrated in tears, saliva and at wounds to bind iron to limit bacterial growth. Egg white contains 12% conalbumin to withhold it from bacteria that get through the egg shell (for this reason prior to antibiotics, egg white was used to treat infections).[9]

To reduce bacterial growth, plasma concentrations of iron are lowered in fever [10], and following surgery after open wounds where it acts as a protection against infection.[11] Reflecting this link between iron bioavailability and bacterial growth, the taking of iron supplements can increase the risk of infection.[12] A moderate iron deficiency, in contrast, can provide protection against acute infection.[13]

References

  1. Wintergerst, E. S., Maggini, S. Hornig, D. H. (2007) "Contribution of selected vitamins and trace elements to immune function". Ann Nutr Metab. 51: 301-323. PMID 17726308
  2. Longmore, Murray; Ian B. Wilkinson, Supaj Rajagoplan (2004). Oxford Handbook of Clinical Medicine, 6th Edn, 626–628, Oxford University Press.
  3. Rockey D, Cello J (1993). Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia. N Engl J Med 329 (23): 1691–5.
  4. Rimon E, Kagansky N, Kagansky M, Mechnick L, Mashiah T, Namir M, Levy S (2005). Are we giving too much iron? Low-dose iron therapy is effective in octogenarians. Am J Med 118 (10): 1142–7.
  5. Kluger, M. J. Rothenburg, B. A. (1979) "Fever and reduced iron: their interaction as a host defense response to bacterial infection". Science. 203: 374-376. PMID 760197
  6. Nesse, R. M.; Williams, G. C.. Why We Get Sick: The New Science of Darwinian Medicine. New York. page 30 ISBN 0-679-74674-9.
  7. T. William Hutchens, Bo Lönnerdal; Lactoferrin: Interactions and Biological Functions (1997). page 379 on Google Books
  8. Nesse, R. M.; Williams, G. C.. Why We Get Sick: The New Science of Darwinian Medicine. New York. page 30 ISBN 0-679-74674-9.
  9. Nesse, R. M.; Williams, G. C.. Why We Get Sick: The New Science of Darwinian Medicine. New York. page 29 ISBN 0-679-74674-9.
  10. Weinberg, E. D. (1984) "Iron withholding: a defense against infection and neoplasia". Physiol Rev. 64: 65-102. PMID 6420813
  11. Ballantyne, G. H. (1983) "Rapid drop in serum iron concentration following cholecystectomy. A metabolic response to stress". Am Surg. 49: 146-150. PMID 6830068
  12. Murray, M. J., Murray, A. B., Murray, M. B. Murray, C. J. (1978) "The adverse effect of iron repletion on the course of certain infections". Br Med J. 2: 1113-1115. PMID 361162
  13. Wander, K., Shell-Duncan, B. McDade, T. W. (2008) "Evaluation of iron deficiency as a nutritional adaptation to infectious disease: An evolutionary medicine perspective". Am J Hum Biol. PMID 18949769

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