Iron deficiency – everything you need to know

THE ROLE OF IRON IN THE BODY

Iron is a key and essential element for all living organisms:

• It is an essential trace element in the process of oxygen transfer, red blood cell formation, DNA synthesis, and the development of the central nervous system;

• Iron also participates in the formation of the myelin sheath of axons, which is necessary for the proper transmission of nerve impulses;

• Iron is necessary for the synthesis of neurotransmitters in the central nervous system such as GABA, glutamic acid, and influences the number of dopaminergic D2 receptors;

• It participates in the regulation of immune system functions (including fighting viruses and bacteria);

• This element is also necessary for the proper vision process;

• Improves liver metabolism;

• Affects insulin sensitivity;

• Regulates cholesterol levels in the body.

Therefore, as can be guessed from the above-mentioned information, iron deficiency significantly and multi-levelly disturbs the functioning of almost the entire body.

IRON DEFICIENCY – SYMPTOMS

As a result of long-term iron deficiency, iron deficiency anemia develops, also known as anemia.

Anemia is a pathological condition in which the total mass of red blood cells and their oxygen-carrying capacity is insufficient to ensure proper oxygenation of tissues and organs, which is accompanied by a multitude of unpleasant symptoms that depend primarily on the severity of the anemia.

Iron deficiency anemia can be classified as mild, moderate or severe depending on the hemoglobin concentration.

Iron deficiency is very common in the Polish population – it affects over 25% of women of reproductive age, approximately 26% of pregnant women, and approximately 26% of preschool children. This is primarily due to insufficient dietary intake of easily absorbable forms of iron and malabsorption disorders (more on this later in this article).

1. paleness of the skin in the mucous membranes of the mouth and throat, conjunctiva, lips, and nail plates;
2. brittleness and concavity of nails;
3. hair loss;
4. headaches and dizziness;
5. decreased appetite;
6. impaired sleep quality;
7. concentration and memory disorders;
8. weakness of muscle strength, lack of energy, excessive sleepiness, loss of energy and easy fatigability;
9. heart rhythm disturbances, palpitations, shortness of breath;
10. hormonal disorders, including in women the pre-ovulatory increase in LH and estradiol levels and an increase in prolactin levels;
11. if iron deficiency anemia lasts longer, more serious symptoms may appear, such as: metabolic changes, manifested by the predominance of systemic catabolism and a decrease in muscle mass, impaired functioning of the immune system, hyperlipidemia, insulin resistance and electrolyte disturbances, changes in the fundus of the eye (including flame-shaped petechiae, exudates, tortuosity of veins) and optic disc edema;
12. Additionally, when anemia occurs suddenly and is severe, fainting and loss of consciousness may occur, and in cases of severe anemia, even coma may develop.

IRON DEFICIENCY DIAGNOSIS

Clinically apparent anemia is very easy to diagnose because a very cheap parameter such as blood count will already show it.

Anemia occurs when the hemoglobin concentration or the total volume of red blood cells (hematocrit) are below the lower limit of normal.

According to the WHO definition, anemia is defined as a decrease in hemoglobin concentration:

• less than 13 g/dl in men;

• less than 12 g/dl in women;

• in pregnant women — less than 11 g/dl.

However, it's important to remember that iron deficiency anemia, as seen in a complete blood count, is a late manifestation of iron deficiency. Determining complete blood counts alone won't reveal the stage of negative iron balance (pre-latent stage), which is the first stage of iron deficiency development. Iron levels in the blood, however, have low diagnostic value because they are highly variable daily and between individuals, and also depend on the type of meals consumed and the presence of iron supplements.

Iron supplied by food is transported by transferrin. Under normal conditions, approximately 70% of absorbed iron is used for hemoglobin synthesis, and most of the remaining 30% is stored in tissues, primarily as ferritin or hemosiderin.

In the pre-latent stage, ferritin concentration, among others, decreases, but as long as iron reserves are sufficient, no changes in morphology or in the results of other iron metabolism parameters such as TIBC and TfS are observed.

Further decline in iron stores (ferritin) results in decreased serum free iron concentration, increased TIBC and decreased TfS.

Continued and worsening iron deficiency initiates the stage of overt anemia observed by a decrease in hemoglobin concentration.

LET'S DECIPHER THESE CONCEPTS

1. Transferrin – the main iron transporter in the blood, a stable parameter that does not show significant daily variation.

Transferrin levels increase in iron deficiency. In conditions associated with excessive iron accumulation, cirrhosis, and malnutrition, transferrin levels are decreased.

2. TIBC - determines the total concentration of iron-binding proteins in the blood, mainly transferrin.

It increases in iron deficiency and decreases in conditions associated with excessive iron accumulation or chronic diseases.

3. UIBC - determines the concentration of iron-binding proteins that have not been bound to it, i.e. mainly the part of transferrin that is not bound to iron at a given moment.

It increases in iron deficiency and decreases in conditions associated with excessive iron accumulation.

4. Transferrin saturation is calculated according to the formula: transferrin saturation (%) = iron concentration × 100/total iron binding capacity (TIBC).

It decreases in iron deficiency or chronic diseases, and increases in conditions associated with excessive iron accumulation.

5. Ferritin – iron is an element essential for life, but its atoms can be toxic to cells, ferritin is a protein that binds iron atoms in a cell-safe manner, protecting tissues from its toxic effects.

Ferritin, therefore, determines the amount of body iron stores, and its level accurately reflects iron reserves during physiological states. Reduced ferritin synthesis is observed only in iron deficiency, but elevated ferritin levels require critical and cautious interpretation, as their levels are also regulated by proinflammatory cytokines such as TNF-α, interleukins IL-1α, and IL-6; their elevated levels can increase ferritin synthesis. Conditions that can lead to excessive ferritin levels include excessive iron accumulation (iron overload, hemochromatosis), anemia associated with chronic disease, acute inflammation, infectious stimuli, cancer, and liver damage. Higher ferritin levels are also observed in individuals with a higher BMI and in those who regularly consume alcohol.

6. An additional very sensitive diagnostic parameter that few people test and many people do not know about is the soluble transferrin receptor (sTfR).

sTfR is a specific and early indicator of iron deficiency. Elevated levels of the soluble transferrin receptor can be detected in each phase of iron deficiency. Soluble transferrin receptor can be quantified and also used in the differential diagnosis between iron deficiency anemia and anemia of chronic disease (ACD). Unlike ferritin, sTfR is not an acute-phase protein, so its concentration is not influenced by inflammatory mediators. Compared to ferritin, it remains within the normal range in ACD.

KEY ASPECTS OF DIAGNOSIS OF IRON DEFICIENCY

Therefore, when assessing iron metabolism, one should take into account not only the blood count or iron concentration in the blood, but also the concentration of transferrin, ferritin, TIBC and transferrin saturation (TfS), and preferably also the soluble transferrin receptor (sTfR).

The highest specificity for the beginning of iron deficiency problems is demonstrated by decreasing ferritin concentration, decreased transferrin iron saturation and increased soluble transferrin receptor (sTfR) level, which is a very sensitive diagnostic parameter that increases in each phase of iron deficiency.