A certain amount of iron is lost through feces (gastrointestinal epithelium) and macrophages that capture iron. It is also lost through urine, 0.1 mg/day (RBC and renal tubular cells (renal epithelium) such as hemosiderin and ferritin). It is lost through hair, desquamated skin, nails, and sweat as well. Women lose up to 18 mg of iron per month through menstruation.
The body has a set of protective mechanisms for binding excess iron in various tissues. In cells, iron is stored by forming complexes with proteins such as: ferritin and hemosiderin.
Apoferritin binds free ferrous iron (Fe2+) and stores it as the ferric state (Fe3+). Once ferritin accumulates sufficiently in SFMN cells, protein aggregates form as hemosiderin. Iron from ferritin and hemosiderin can be mobilized from SFMN cells and used, although hemosiderin is less readily available.
In stable conditions, ferritinemia (the serum ferritin level) correlates with the total body iron stores, hence ferritinemia is the most convenient laboratory test to estimate iron stores. The value of ferritinemia is not affected by one or several dietary or medicinal intakes, knowing that its theoretical correction (if the cause is eliminated and treatment with iron preparations or foods with the therapeutic dose of iron is performed) requires 6 weeks.
The value of Sideremia (ferremia) in the assessment of iron stores (i.e., in diagnosing Iron Deficiency), is not useful, because it has daily fluctuations (depends on the amount of iron in the diet), is affected by iron-containing medications, iron dietary supplements, is affected by the metal part of the needle for blood collection and decreases in the presence of inflammation.
In SFMN (macrophages of the bone marrow, spleen, liver, etc.) Fe is stored as Ferritin and Hemosiderin. Ferritin is a protein composed of 24 subunits (apoferritin), which has a spatial configuration like a shell around a central cavity that contains up to 2500 (4000) atoms of Fe3+ (the oxidized form of iron). Hemosiderin is an aggregate of ferritin molecules. 65% of iron reserves are in the form of ferritin and 35% in the form of hemosiderin.
Organized in the form of ferritin (a protein complex), iron becomes water-soluble and does not disintegrate into ions. Circulating plasma ferritin represents only 10% of the total ferritin and is the main indicator to show the Fe reserves in the body. In the setting of anemia, serum ferritin is the most sensitive lab test for iron deficiency anemia.
The normal range of Ferritinemia is 20-320 ng/ml or µg/l. Ferritinemia less than 20 ng/ml (for some 15 or 12 ng/ml) is equivalent to IDA. Hemosiderin represents a more stable form for iron deposits and hence less usable, compared to ferritin. Only when there is continuous mobilization of iron stores will the hemosiderin stores decrease. Iron reserves in females in the reproductive period are about 600 mg and in males about 1200 mg (twice as much).
Regulation of the necessary amount of iron absorption (iron uptake) in the G-I Tract
Normally, only a small amount of iron is lost daily with the exfoliated epithelium (that falls) of the skin and mucous membranes (in the fluids of the Gastro-Intestinal, Respiratory, Urogenital systems), so the control of iron levels in the body is almost regulated by its regular capture and absorption from the Gastro-intestinal Tract which should be emphasized is perfect, thus absorbing as much iron as the body needs or simply as much as it loses, maintaining a stable balance.
However, when a large amount of iron is taken orally, there may be an increased level of iron in the blood because a large amount of iron will damage the cells of the G-I Tract (enterocytes) excluding them from the perfect regulation in iron absorption. High concentrations of iron in the blood damage the cells of the liver, heart, skin, pancreas with serious consequences, chronic damage, and death.
Excessive amounts of iron are toxic, because free 2-valent iron [Fe2+] reacts with peroxides to produce free radicals, which are very reactive and can damage DNA, proteins, lipids, and other cellular components. Thus, iron toxicity occurs when there is free circulating iron and in cells, which only happens when iron levels exceed the binding capacity of transferrin for iron.
As we emphasized above, in healthy individuals, the concentration of iron in the body is perfectly regulated by the absorptive cells (enterocytes) of the proximal part (jejunum) of the small intestine.
Thus, enterocytes regulate the absorption of iron obtained through various foods, depending on the daily amount of iron loss (the daily amount of iron absorption equals the daily loss) to maintain a continuous iron balance. Persistent errors in iron balance cause;
1. Iron Deficiency (when there is a negative balance of it), which if not corrected in time can also cause Iron Deficiency Anemia.
2. Hemosiderosis and Hemochromatosis (positive balance of it).
Both balances have consequences for humans. The human body is perfectly built to have a certain physiological amount of iron that should circulate, be used, and only stored when bound to other structures (proteins in most cases) and should not have any free iron either in circulation or in cells due to its toxic action.
Iron deficiency is the reduction of the total content of this microelement (iron) in the body, due to a negative balance between the amount taken and that eliminated.
* Iron Deficiency Anemia occurs when the iron deficiency is so severe that it reduces erythropoiesis and causes the development of anemia (iron-restricted erythropoiesis).
* Iron Deficiency without Iron Deficiency Anemia is more common than Iron Deficiency with Iron Deficiency Anemia.
It is thought that anemia from iron deficiency (and also from Vitamin B12 deficiency, Folic Acid, etc.) are related to their not being taken with food (or different diets that people maintain). These anemias are actually also called nutritional or dietary anemias, but in fact, at least nowadays, the possibility of their deficiency being caused by not taking these elements with food is very small.
This is because in both developed and developing countries, plant and animal foods are consumed (where iron and other components necessary for erythrocyte synthesis are found) and a certain amount of iron passes into the food also from the iron-containing pot in which the food is prepared.
Therefore, not taking the required amounts is a factor, but not significant. It is a problem that can be controlled and corrected (using supplements or fortifying iron in water, milk, biscuits, etc.).
It can be caused by reduced absorption in various Gastro-Intestinal Tract pathologies (gastritis, malabsorption, etc.), by congenital or acquired pathologies in iron transport in enterocytes of the intestine and then in the blood to the places of its use. It should be emphasized that under normal conditions, the absorption of iron in the Gastro-Intestinal Tract is perfect (meaning that iron will be absorbed according to the body's needs, so the less iron there is, the more will be absorbed and vice versa).
But the main cause of the reduction of iron reserves (iron deficiency) is its loss, primarily through various forms of hemorrhage, which in most cases are very small (visible to the eye and often underestimated and sometimes not visible to the eye but discovered with the help of a microscope or different tests), but prolonged over time.
Large hemorrhages deplete the iron stores, but they are such that they prompt the patient to go to the doctor and are generally treated with blood replacements (and Red Blood Cell Mass or Whole Blood that ensures the introduction of iron amounts into the body not through the usual enteral route, but parenterally, I/V).
We emphasize hemorrhages, because it is precisely the iron that gives blood its red color (and this same color to the muscle, hence meat). IDA is often called anemia from hemorrhage. There may be a combination of all causes (multifactorial).
Iron deficiency is the most likely nutritional problem to be prevented. It is almost eliminated in developed countries, but 750 million children in the developing world have IDA. In most cases, a patient goes to the doctor only when Iron Deficiency Anemia is discovered, so the period with Iron Deficiency is often not evaluated, not diagnosed (ferritinemia is the main analysis), its cause not discovered and not treated in practice.
It is important not only to treat Anemia and Iron Deficiency but also to discover the cause, not of anemia (which in this case the cause is known to be iron deficiency), but of Iron Deficiency.
Anemia from absolute iron deficiency, or anemia from true iron deficiency where there is inhibition of heme production of Hb and erythropoiesis as a consequence of the absolute lack of iron (hypoferremia) to distinguish it from Chronic Inflammatory Anemia where there is excess iron in the body, stored in SFMN, but cannot be used for the synthesis of heme of Hb, consequently still reducing erythropoiesis.
Erythrocytes are one of the most perfect cells of the body because they do not have a nucleus (are destined to die after performing their function), do not have organelles (mitochondria, ribosomes), take the form of a biconcave disk to ensure the largest surface area for a given volume, provide the necessary energy from not very effective pathways such as anaerobic glycolysis performed in the cytoplasm, will pass many times a day in microcirculation (mechanical and hypoxic stress), every 20 seconds makes a circulation throughout the body and all this for 120 days (4 months).
Therefore, this "cell" has almost completely emptied its cytoplasm to fill it with a main pigment, hemoglobin, which is composed of 4 protein chains, each linked to a prosthetic group (heme) that has an iron atom in the center. The same prosthetic group (heme) is found in myoglobin in muscles. It is the hemoglobin of erythrocytes and precisely the iron atom that will transport oxygen to all tissues.
Iron deficiency in the body will be followed among others by a reduction of hemoglobin in red blood cells. Precisely the quantitative reduction of hemoglobin is known as anemia and, highlighting the cause, the anemia will be classified as ferrodeficiency. This is reflected from the laboratory side, with the decrease of all red series indicators and in the peripheral blood smear red blood cells (erythrocytes) appear less pigmented and smaller than normal (hypochromic, microcytic anemia).
The reduction of iron in the body will also be accompanied by a reduction of hemoglobin and myoglobin in muscles, resulting in improper oxygen transport to all cells, hence limiting their function, not realizing oxidative phosphorylation (careful there's no ATP!!! because iron serves as a coenzyme of the enzymes of the cellular respiration chain), which takes place in mitochondria.