Iron-Deficiency Anemia: Pathogenesis, Labs & Features

Q: What morphological erythrocyte changes are characteristic of iron-deficiency anemia?

Iron-deficiency anemia (anemia ferripriva) features specific morphological erythrocyte changes indicating impaired hemoglobin synthesis: Hypochromia (Hypochromia) — marked expansion of the central pallor zone, leaving only a narrow peripheral rim colored ("ring-shaped" erythrocytes, or "shadows", annulocytes).Microcytosis (Microcytosis) — reduction in the diameter and mean volume of erythrocytes.Anisocytosis — variation in cell size with a predominance of microcytes.Poikilocytosis — variation in cell shape. In severe deficiency, ovalocytes and rod-shaped forms may appear.

Iron-Deficiency Anemia

Anemia sideropenica

For medical students2 min readUpdated 2026-10-10

Iron-deficiency anemia is a pathological condition in which reduced iron levels in the body lead to impaired hemoglobin synthesis and tissue hypoxia. The disease is accompanied not only by hematological shifts, but also by systemic organ damage due to a deficiency of iron-containing enzymes.

Color indexDecreased (marked erythrocyte hypochromia develops)

Serum ironLevel drops, ferritin stores are depleted

TransferrinContent and TIBC compensatorily increase

Tissue deficiencyLeads to nail brittleness, hair loss, and glossitis

Etiology: Why Does Deficiency Occur?

The development of iron deficiency is caused by an imbalance between iron intake and the body's requirements. Several main groups of causes are distinguished:

Dietary deficiency (nutritional factor).
Chronic blood loss. Most commonly gastrointestinal, uterine, or urinary tract bleeding.
Increased demand. Characteristic of rapid growth periods: in infants with high birth weight, during the second half of the first year of life, and in the prepubertal and pubertal periods.
Transport disorders. Reduced level or activity of the carrier protein — transferrin.
Hormonal imbalance disrupting micronutrient metabolism.

In children, specific factors also play a role: antenatal factors (fetoplacental insufficiency, significant iron deficiency in the pregnant mother) and intranatal factors (birth hemorrhage, premature placental abruption, umbilical cord rupture).

Pathogenesis: Two Pathways of Damage

Iron deficiency triggers two parallel pathological cascades in the body:

Hematological pathway. In the mitochondria of bone marrow erythroid cells, heme synthesis is inhibited. This disrupts its binding to globin and leads to decreased hemoglobin production. The result is anemia and tissue oxygen starvation (hypoxia).
Tissue (metabolic) pathway. The synthesis of other iron-containing compounds suffers: myoglobin, cytochromes, peroxidases, and catalase. Due to the drop in antioxidant factor activity, lipoperoxidation (lipid peroxidation) increases, which directly damages parenchymal organ cells.

Hematological Picture

Hematopoiesis in this pathology remains normoblastic, but undergoes a number of changes.

In the bone marrow, moderate hyperplasia of the erythroid lineage is observed. A characteristic sign of inhibited erythropoiesis is an increase in the number of basophilic and polychromatophilic erythroblasts against a background of deficient orthochromatic normoblasts. The number of sideroblasts (normoblasts with granules of stored iron) drops sharply.

In the peripheral blood, the following are detected:

Erythropenia (decreased red blood cell count) and pronounced hypochromia (drop in color index).
Anisocytosis (smaller cells — microcytes — predominate) and poikilocytosis (change in shape).
Appearance of erythrocyte "shadows" (annulocytes) — cells with an extremely low hemoglobin content.
Reticulocyte count may be increased in the initial stages, but falls or remains normal in chronic courses.
Leukopenia (predominantly due to neutropenia) with a normal platelet count.

Biochemical blood analysis shows a drop in serum iron and ferritin, while transferrin levels and total iron-binding capacity (TIBC) increase.

Tissue Manifestations (Sideropenic Syndrome)

Symptoms consist of manifestations of tissue hypoxia and a shortage of iron-containing enzymes.

Muscular system: Myasthenia (muscle weakness) develops due to a deficiency of myoglobin and tissue respiration enzymes.
Skin and skin appendages: Peeling, cracks in the skin and mucous membranes, hair loss, and specific nail deformation — koilonychia (increased brittleness) are characteristic.
Gastrointestinal tract: Dystrophic changes in the walls of the digestive tract lead to hypotrophic glossitis, gastritis, and enteritis.

Differential Diagnosis: Iron-Refractory Anemias

It is important to distinguish true deficiency from iron-refractory (sideroblastic, porphyrin-deficient) anemias. In these conditions, iron is present in the body (sometimes in excess), but due to genetic defects or toxic exposure, it is not incorporated into the heme molecule.

Examples of such conditions include:

Vitamin B6 deficiency, which disrupts iron incorporation into heme.
Lead poisoning (saturnism). Lead blocks sulfhydryl groups of enzymes involved in protoporphyrin synthesis. As a result, urinary aminolevulinic acid levels spike, and erythrocytes with basophilic stippling appear in the blood.
Thalassemias — a group of disorders characterized by impaired globin chain synthesis.

The main difference between these forms and classic iron-deficiency anemia is an increased level of serum iron and ferritin with normal transferrin and TIBC levels.

Mnemonic

To remember the biochemistry of true iron-deficiency anemia, use the seesaw rule: "Iron and ferritin fall down, while transferrin and TIBC fly up, trying to catch the leftovers."

Frequently asked questions

What stages of iron deficiency are distinguished in pathophysiology?

In pathophysiology, the process of iron store depletion occurs sequentially and includes four stages:

Hypoferremic stage — initial phase with a drop in iron levels while erythrocyte count and morphology remain normal.
Heterogeneous stage — onset of impaired erythropoiesis with the appearance of erythrocytes of varying diameters (anisocytosis).
Microcytic stage — progression of deficiency with a general decrease in mean corpuscular volume (microcytosis).
Anemic stage — final phase with a drop in hemoglobin levels, representing the manifestation of iron-deficiency anemia.

What morphological erythrocyte changes are characteristic of iron-deficiency anemia?

Iron-deficiency anemia (anemia ferripriva) features specific morphological erythrocyte changes indicating impaired hemoglobin synthesis:

Hypochromia (Hypochromia) — marked expansion of the central pallor zone, leaving only a narrow peripheral rim colored ("ring-shaped" erythrocytes, or "shadows", annulocytes).
Microcytosis (Microcytosis) — reduction in the diameter and mean volume of erythrocytes.
Anisocytosis — variation in cell size with a predominance of microcytes.
Poikilocytosis — variation in cell shape. In severe deficiency, ovalocytes and rod-shaped forms may appear.

How does the blood picture in iron-deficiency anemia differ from iron-refractory forms?

In true deficiency, serum iron is decreased, whereas in iron-refractory forms (e.g., lead poisoning), it is elevated because iron cannot be incorporated into heme and accumulates in the plasma.

Why do muscles, skin, and mucous membranes suffer in iron deficiency?

Iron is a component not only of hemoglobin, but also of muscle myoglobin and tissue enzymes (cytochromes, catalase, peroxidases). Their deficiency causes muscle weakness and epithelial dystrophy.

What are sideroblasts and how does their number change in iron deficiency?

Sideroblasts are bone marrow erythroblasts (normoblasts) containing granules of stored iron. In iron deficiency, their number decreases predictably.

Go deeper

Pathogenesis of primary iron-refractory anemias (genome defects of the erythroblastic lineage).
Mechanisms of lead poisoning development and blockade of porphyrin synthesis enzymes.
Clinical picture of lead encephalopathy, polyneuritis, and gastrointestinal lesions.
Thalassemias: classification by globin chains and hematological manifestations.
Role of vitamin B6 in iron metabolism and consequences of its deficiency.