Clinical Consequences of Iron Deficiency (Part Three)

So, you can live in a room filled with oxygen (it is said that without oxygen there is no life due to its significant structural and functional role in the organism), but without iron, oxygen will not reach the cells of the organism to perform its functions (where the most important is exactly oxidative phosphorylation that ensures the production of large amounts of ATP in mitochondria), so without iron there will be no life (as an oxygen transporter and accelerator of vital reactions of the organism).

These functions of iron should be emphasized, because iron deficiency and its consequences, one of which is Iron-Deficiency Anemia, are the most common in the World (both deficiency and anemia), are very common in medical practice, attempted to be treated by everyone, but in most cases not properly.

Treat Iron Deficiency and Iron-Deficiency Anemia properly, or refer immediately to a specialist. Keep in mind, that small, repeated blood losses, resulting in Iron Deficiency and subsequently Iron-Deficiency Anemia, can be caused by a cancer of the mucosa of all body systems.

In our medical practice and popular treatments, anemia is treated (iron deficiency in most cases is not evaluated at all, despite and as we will see below it has a clinic, so it is not so hidden), while the cause (in this case cancer which is malignant by definition) develops normally. And then to think of another fact, that anemia (regardless of what type and origin it is) should be corrected with foods containing iron (liver, red wine, etc.), mistakes follow one another.

Iron-Deficiency Anemia is the most common anemia in the World and very common among females in the reproductive period due to the continuous hemorrhage of the menstrual cycles. So, in general, it is based on the loss of iron for various reasons (mostly through blood), resulting in the reduction of its reserves in the organism (accurately assessed through ferritinemia) and then clinically and laboratory manifestations appear.

This means that if the cause is removed and the stores are replenished (through treatment that continues for at least 3 months) the anemia is cured and does not recur. If the cause persists, despite the replenishment of the stores, the anemia will recur.

Clinical consequences of iron deficiency in the organism

Stages of iron deficiency. Laboratory tests help in the staging of IDA.

Stage 1. When the organism is in a status of negative iron balance, there will initially be a decrease in iron stores in the BM (ferritin and hemosiderin) that will be mobilized for the synthesis of Hb (and other enzymes containing iron). The compensatory increase in iron absorption will cause an increase in the binding capacity of iron in transferrin. When deposits decrease, iron absorption from the GI mucosa increases. On the other hand, clinic and laboratory changes have not yet appeared (and serum iron continues to stay in almost normal values). Hb and serum iron (iron stores) remain normal, but ferritinemia drops < 20 ng/mL (< 15 μg/l), in BM with Perls staining no iron is detected.

Stage 2. Normal erythropoiesis is inhibited. Although the level of transferrin (iron-binding capacity) is increased, serum iron decreases, transferrin saturation decreases. Erythropoiesis is inhibited when serum iron drops < 50 μg/dL (< 9 μmol/L) and transferrin saturation falls less than 16% (15%). The level of serum ferritin receptors increases (> 8.5 mg/L).

Stage 3. Anemia develops with normal appearance of RBC and normal indicators. There will be development of specific ferrodeficiency erythropoiesis, but Hb, MCV, MCH continue to remain still in normal values (it takes 3 months for normochromic, normocytic RBC to be replaced with hypochromic, microcytic RBC). In this phase (thus low ferritinemia and lacking clinic) if iron is added to therapy, laboratory changes are quickly corrected. Thus when we observe hypochromia, microcytosis iron deficiency has been installed for at least 3 months.

If the cause persists, thus the iron balance is negative and no iron medication is taken, there will be development of the clinic and laboratory of iron-deficiency anemia. Thus, for iron-deficiency anemia to appear, the Fe stores must be completely empty (ferriprive, deprived, in absence of iron, from the deficiency of iron).

If the stores are empty, but anemia has not set in then take medication until the stores are replenished, thus at least 6 weeks.

Stage 4. Microcytosis and hypochromia develop.

Stage 5. Iron deficiency affects tissues with specific symptoms and signs. In this phase, all signs of iron-deficiency anemia appear, which are general signs and symptoms of the anemic syndrome, but there are also some specific signs and symptoms of the lack of iron in the organism such as:

The clinical consequences of iron deficiency are; non-hematological because as we said above, initially Iron Deficiency appears (evaluated with hypoferritinemia) and if this condition persists (thus the cause/causes are not eliminated and the Deficiency corrected) hematological ones will also appear (Anemic Syndrome - Iron-Deficiency Anemia).

1. Clinic of non-hematological changes from iron deficiency (Clinical manifestations that are not related to anemia, but to iron deficiency).

A. From Iron Deficiency due to the compromise of enzyme function and myoglobin there will be fatigue and breakdown. Iron deficiency and superimposed anemia limit physical performance, coping with work and spontaneous physical activity, resulting in decreased productivity and economic loss. It has been observed that in athletes with iron deficiency, but with normal Hemoglobin (nonanemic iron deficiency) the use of iron preparations for correcting its stores, will be accompanied by improvement in work performance and of VO2max.

Iron-Deficiency Anemia decreases work performance where muscle strength is required, compared to healthy people in anaerobic metabolism. Fatigue and reduced ability to cope with heavy work are related to the decrease in Hb, but they are not proportional to the degree of anemia (it depends on the speed of anemia installation and the age of the patient). This means that they are also related to the function of proteins (enzymes) that require iron to perform their function, thus they are more related to the deficiency of iron in iron-enzymes of cellular respiration than from anemia.

B. Epithelial changes (the cells that suffer the most from the lack of iron are those with rapid proliferation such as BM cells, skin epithelium, and mucous membranes. Nonetheless, they are not specific only to the lack of iron, but also in other deficiencies such as Vitamin B12, Folic Acid, Vitamin B6, and in diseases that are not related to micronutrient and vitamin deficiencies).

Hair loss. Hair becomes thin, fragile, and falls out. Thus, the hair does not fall out from anemia, but from iron deficiency. If a patient comes complaining about hair loss, ferritinemia should also be searched.

Cracking of the corners of the mouth. Angular stomatitis (cheilosis) is less specific for iron-deficiency anemia compared to changes in the nails, because it also appears in cases of riboflavin (Vitamin B2) and pyridoxine (Vitamin B6) deficiencies.

Nails initially are thin, fragile, with longitudinal striations and later koilonychia appears (thus taking the shape of a spoon).

Atrophic Glossitis. Shiny, pale, wet, shiny, flat (smoothed) tongue due to atrophy of the papillae, with various degrees of redness. They have burning, pain in different degrees, which can be spontaneous and after eating food and liquids. The changes in the epithelium of the tongue return after 1-2 weeks from the start of treatment.

Dry mouth. Iron Deficiency hampers the protection provided by the Peroxidase System (H2O2) in saliva and decreases the quantity of secreted saliva (dry tongue).

Sideropenic dysphagia (difficulty in swallowing food). Dysphagia is initially for solid foods and later also for liquid ones. The most pronounced changes appear in the place of passage from the oropharynx to the esophagus and can be localized in a certain area, but can also surround the entire diameter and causing stricture. The cause of these specific signs is related to the deficiency of Fe in the epithelial enzymes. Iron-deficiency anemia due to the consumption of Fe in epithelial enzymes becomes also a cause for the development of atrophic gastritis.

C. Neuromuscular System. Even a mild degree of iron-deficiency anemia is accompanied by involvement of muscle function (evaluated with exercise tests). Muscles suffer due to the reduction of their oxygenation not only from the deficiency of hemoglobin but also of myoglobin. The patient complains of quick muscle fatigue. Work performance, prolonged activity are also affected and improve when adequate treatment of anemia is done.