Australian Doctor Australian Doctor 27th October 2017 | Page 20

Iron homeostasis

How to Treat – Iron deficiency

Iron homeostasis

A TYPICAL, healthy adult will have a total body iron store of 3-4g. Approximately two-thirds( 2.5g) of this will be bound to haeme molecules within the four globulin subunits of haemoglobin. The remainder( 1-1.5g) will be stored in the form of ferritin either within the reticuloendothelial system of the liver, spleen and bone marrow, and incorporated into myoglobin or cytochromes enzymes. Only a very small amount of iron circulates in the plasma( 3mg) and it is bound to transferrin. 1, 2
Adult males and non-menstruating women lose 1mg of iron per day, while menstruating women can lose an additional 1mg per day through menstrual blood loss. 2, 3
The average Western diet contains 5mg of iron per 1000 calories consumed in one of two forms: haeme-iron from animal products, by a mechanism that remains poorly understood; and non-haeme iron, from cereals and vegetable products.
Not surprisingly, the bioavailability of haeme-iron is significantly higher than that of non-haeme iron( 30 % vs 10 %). 1-3
However, humans have evolved an exceptionally efficient method of conserving iron by recycling liberated iron from the breakdown of old red blood cells, such that 5 % of our iron needs to be
obtained from dietary sources. 1, 2
During times of stress, such as iron deficiency or increased erythropoietic demand, the intestinal absorption of iron can be increased by three- to fivefold to cope with the increased demand for iron. This is achieved by the downregulation of the hepatic hormone hepcidin. This downregulation allows the increased expression of ferroportin, a receptor on the basolateral membrane of enterocytes in the proximal small bowel. Ferroportin allows the iron to enter the circulation, where it then binds to transferrin for delivery to where it’ s needed, such as the bone marrow for erythropoiesis.
However, when iron stores are plentiful or during times of inflammation, infection or disease, the liver upregulates the production of hepcidin, which prevents the release of iron into the circulation by decreasing the expression of ferroportin. The absorbed iron is then stored as ferritin within the enterocyte, until it is sloughed off into the lumen of the gut for excretion in the faeces. 1, 4
Therefore, the human body has only one mechanism by which it can maintain iron homeostasis: the regulation of oral iron absorption from the gastrointestinal tract via hepcidin( see figure 1).
Inflammation and infection
Hepcidin induced by IL-6 and LPS
Hepcidin synthesis
Iron recycling in the liver and spleen( 30mg of iron daily)
Inhibition of hepcidin synthesis
Iron in food
Inhibitory action of hepcidin
Red blood cells
Duodenal absorption
Plasma irontransferrin
Erythropoiesis in the bone marrow
Figure 1. Iron homeostasis.

Epidemiology
THE WHO ESTIMATES THAT AROUND 30 % OF THE WORLD’ S POPULATION IS AFFECTED BY IRON DEFICIENCY.
THE WHO estimates that around 30 % of the world’ s population is affected by iron deficiency. 3 Numerous public health campaigns have been developed to identify and treat this epidemic that currently affects more than two billion people, particularly women, children and those from the lowest socioeconomic communities.
There is considerable variation in individuals’ iron requirements based on age, sex and comorbidities
. Infants frequently develop iron deficiency due to poor oral intake of iron-rich foods, while increased physiological demand for iron during childhood, adolescence and pregnancy often render these patients deficient, despite an otherwise adequate iron intake. However, pathological processes seen with increasing age— such as malignancy, gastrointestinal disease and chronic inflammatory conditions— are frequently
responsible for iron deficiency in older adults.
Only a few Australian studies have reported the incidence and prevalence of iron deficiency or iron deficiency anaemia, and they have all been performed in highrisk populations. Studies in the late-1990s and early-2000s suggested that 1-6 % of toddlers were iron deficient, with even higher rates in some ethnic groups( 14 % of Asian toddlers). 2 It has been estimated
around 10 % of all young women not taking iron supplementation are iron deficient, however, rates can be as high as 25 % during pregnancy in some communities. 2
The rates of iron deficiency and iron deficiency anaemia appear disproportionately high in Indigenous Australians. A study performed in a remote north-west WA community identified anaemia in 55 % of Indigenous women and 18 % of Indigenous men. 2

Pathogenesis
Infants and young children IRON deficiency is the most common nutritional deficiency in infants and young children. 5 Their dietary iron intake is frequently inadequate to maintain sufficient iron stores during periods of rapid growth spurts associated with increased lean body mass and red cell expansion. Table 1 lists the iron requirements for infants and young children.
Term infants require 0.5-1mg of iron per day to double their red cell mass within 12 months, in addition to the 200-250mg of iron that they had accumulated during gestation.
Infants solely drinking cows milk are susceptible to iron deficiency as it contains as little as 0.5mg / L of poorly available iron. Up to 20-40 % of infants( aged six months and over) fed predominantly cows milk, non-fortified formula or breastfed for prolonged periods without the introduction of solids will develop iron deficiency. 5
Cows milk has also been associated with increased intestinal blood loss secondary to cow’ s milk protein-induced colitis.
In addition, young children may still be at increased risk of iron deficiency despite a‘ balanced diet’, as non-haeme iron in the form of cereals and breads are the major caloric component of their diet compared with adult diets. 5
Table 1. Recommended iron requirements for infants and young children Age Requirement Strategies to meet requirements Preterm infant
Term infant
2-4mg / kg per day to a maximum of 15mg / kg
0.5-1mg / kg per day to a maximum of 15mg / kg
Addition of iron supplementation from one month in breastfed infants or the use of iron-fortified pre-term formula. Cows milk should be avoided until after 12 months.
Addition of iron supplementation from four months in breastfed infants, then introduce iron-fortified cereals or iron-fortified formula. Cows milk should be avoided until after 12 months.
Child 1-3 years
7-9mg per day
Balanced diet with adequate amounts of iron rich foods( more than three serves / day). Should not consume more than 600mL of cows milk per day.
Child 4-8 years
10mg per day
Balanced diet.
Child 9-13 years 8mg per day Balanced diet. Source: Pasricha et al. Medical Journal of Australia 2010; 193:525-32.
Adolescents Iron deficiency can develop during adolescence, because of the increased physiological demand for iron due to rapid expansion of muscle mass and red cell volume during this period.
Interestingly, research shows that girls and young women physiologically have the lowest hepcidin levels, which don’ t reach the levels seen in males until menopause. This is thought to be an evolutionary mechanism to maximise dietary iron absorption in those at highest risk of developing iron deficiency. 4, 6
Adolescent males tend to have an intense, but transient, physiological increase in iron requirements following the onset of sexual maturation, after which, iron demands rapidly return to baseline. Adolescent females have a gradual, but continued, increase in iron requirements into adulthood. This is because of the increased physiological demand of puberty and the continued blood loss associated with menstruation.
Recommended iron requirements for adolescents appear in table 2. Adolescents at risk of developing iron deficiency are listed in box 1. cont’ d page 22
20 | Australian Doctor | 27 October 2017 www. australiandoctor. com. au