Table of Contents
Pica and Pagophagia
One of the most curious and specific signs of iron deficiency is Pica (appetite for non-nutritive substances). The most common form is Pagophagia (compulsive desire to chew ice). Studies suggest that chewing ice may increase cerebral blood flow in anemic patients, transiently improving alertness, although the exact mechanism remains a neurobiological mystery.
1. Introduction: The Global Hidden Hunger
Iron deficiency is the most prevalent nutritional deficiency in the world, affecting about 30% of the global population, according to the WHO. Although often associated with developing countries, it remains an underdiagnosed cause of chronic fatigue, decreased intellectual performance, and exercise intolerance in developed nations.
Iron deficiency anemia is not a disease in itself, but a sign of something underlying (bleeding or malabsorption). Treating anemia without investigating the cause is considered medical malpractice, as it may mask serious conditions such as colorectal cancer or celiac disease.
2. Pathophysiology: No Iron, No Energy
Iron is an essential mineral, but toxic if free in the body. Therefore, it is tightly controlled by transport proteins (Transferrin) and storage proteins (Ferritin).
Vital Functions of Iron
- Oxygen Transport: Central component of the Heme group in Hemoglobin (blood) and Myoglobin (muscle). Without iron, O2 transport fails.
- Cellular Respiration: Essential for cytochromes in the mitochondrial electron transport chain. Lack of iron reduces ATP (energy) production even before anemia appears.
- DNA and Neurotransmitter Synthesis: Cofactor for enzymes that synthesize dopamine and myelin.
3. Signs and Symptoms: The Body Calls for Help
Symptoms develop slowly, allowing the body to adapt to hypoxia. When the patient seeks help, depletion is already severe.
| Sign/Symptom | Pathophysiological Mechanism |
|---|---|
| Extreme Fatigue | Tissue hypoxia and mitochondrial dysfunction (less ATP). |
| Restless Legs Syndrome | Dopaminergic dysfunction in the CNS dependent on iron. Affects up to 25% of anemic patients. |
| Koilonychia | Spoon-shaped nails (concave), thin and brittle. Sign of severe chronic deficiency. |
| Atrophic Glossitis | Smooth, red, and painful tongue due to loss of papillae (epithelial atrophy). |
| Hair Loss | The hair follicle is highly sensitive to lack of ferritin, entering the telogen (shedding) phase early. |
4. Etiology: Where is the Iron?
The human body does not have a physiological mechanism for active iron excretion. Therefore, deficiency occurs through only three pathways:
- Increased Demand: Pregnancy (fetus consumes iron), childhood/adolescence (rapid growth).
- Decreased Absorption: Atrophic gastritis (lack of acid), chronic use of proton pump inhibitors (Omeprazole), Celiac Disease, bariatric surgery.
- Blood Loss (Most Common):
- Women: Excessive menstruation (menorrhagia).
- Men and Postmenopausal Women: Gastrointestinal bleeding (ulcer, polyp, cancer, angiodysplasia) is the mandatory cause to investigate.
5. Laboratory Differential Diagnosis
The blood count shows Microcytic (low MCV - small red blood cells) and Hypochromic (low MCH - pale red blood cells) anemia. RDW (anisocytosis index) is usually elevated, indicating variation in cell size.
The main differential diagnosis is with Thalassemia Minor (genetic) and Anemia of Chronic Disease (inflammation). The Iron Profile clarifies:
| Parameter | Iron Deficiency Anemia | Anemia of Chronic Disease | Thalassemia Minor |
|---|---|---|---|
| Ferritin | Low (< 30 ng/mL) | Normal or High (Acute phase reactant) | Normal |
| Serum Iron | Low | Low (Sequestered) | Normal |
| TIBC (Binding Capacity) | High (Iron hunger) | Low | Normal |
| Transferrin Saturation | Low (< 20%) | Low or Normal | Normal |
6. The Ferritin Dilemma
Ferritin is the best marker of iron stores, but it is also an acute-phase protein. In inflammatory states (infection, obesity, arthritis), ferritin rises falsely, masking a real iron deficiency.
In these cases, Transferrin Saturation and Soluble Transferrin Receptor are more reliable markers. A ferritin < 30 ng/mL is diagnostic of absolute iron deficiency, but in inflamed patients (e.g., heart failure), the cutoff rises to < 100 ng/mL.
7. Treatment: The Art of Replacement
The goal is to normalize hemoglobin and, crucially, replenish stores (ferritin), which takes months.
Oral Replacement
Ferrous Sulfate is the classic, but causes many gastrointestinal effects (pain, constipation, nausea). New formulations like Iron Polymaltose or Bisglycinate are better tolerated and absorbed, allowing greater adherence. Current recommendation is alternate-day dosing (e.g., Mon, Wed, Fri) to decrease Hepcidin (hormone that blocks iron absorption) and improve tolerance.
Intravenous (IV) Replacement
Indicated for those who cannot tolerate oral, have malabsorption (bariatric, inflammatory bowel disease), or need rapid replenishment (heart failure, pre-operative). Modern formulations like Ferric Carboxymaltose are safe and allow infusion of high doses in 15 minutes.
8. Diet: Heme vs Non-Heme Iron
Diet prevents, but rarely cures established anemia. There are two types of iron:
- Heme Iron: Present in red meat, liver, chicken, and fish. High absorption (20-30%) and direct, not influenced by other foods.
- Non-Heme Iron: Present in vegetables (beans, lentils, spinach). Low absorption (2-5%) and dependent on cofactors.
Golden Tip: Vitamin C (orange, lemon) in the same meal increases non-heme iron absorption by up to 3x. Calcium (milk, cheese), tannins (tea, coffee), and phytates inhibit absorption and should be consumed away from main meals.
9. Conclusion
Iron Deficiency Anemia is a warning sign from the body that should not be ignored or treated empirically without investigation. Restoring iron levels not only corrects anemia but returns vitality, cognitive capacity, and quality of life. Accurate diagnosis of the underlying cause is the most important step in treatment.