Iron deficiency anaemia Sequence of events

Depletion of iron stores

When the body is in a state of negative iron balance, the first event is depletion of body stores, which are mobilized for haemoglobin production. Iron absorption is increased when stores are reduced, before anaemia develops and even when the serum iron level is still normal, although the serum ferritin will have already fallen.

Iron-deficient erythropoiesis

With further iron depletion, when the serum ferritin is below 15 |ig/L, the serum transferrin saturation falls to less than 15% due to a rise in transferrin concentration and a fall in serum iron. This leads to the development of iron-deficient erythropoiesis and increasing concentrations of serum transferrin receptor and red cell protoporphyrin. At this stage, the haemoglobin, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) may still be within the reference range, although they may rise significantly when iron therapy is given.

Iron deficiency anaemia

If the negative balance continues, frank iron deficiency anaemia develops. The red cells become obviously microcytic and hypochromic (Figure 3.5c), and poikilocytosis becomes more marked. The MCV and MCH are reduced, and target cells may be present. The reticulocyte count is low for the degree of anaemia. The serum TIBC rises and the serum iron falls, so that the percentage saturation of the TIBC is usually less than 10%.

The number of erythroblasts containing cytoplasmic iron (sideroblasts) is reduced at an early stage in the development of deficiency, and siderotic granules are entirely absent from these cells when iron deficiency anaemia is established. The erythro-blasts have a ragged, vacuolated cytoplasm and relatively pyknotic nuclei. The bone marrow macrophages show a total absence of iron, except where very rapid blood loss outstrips the ability to mobilize the storage iron. Platelets are frequently increased.

Tissue effects of iron deficiency

When iron deficiency is severe and chronic, widespread tissue changes may be present, including koilonychia (ridged nails, breaking easily), angular stomatitis (especially in those with badly fitting dentures), glossitis (hair thinning) and pharyngeal webs (Paterson-Kelly syndrome). Partial villous atrophy, with minor degrees of malabsorption of xylose and fat, reversible by iron therapy, has been described in infants suffering from iron deficiency, but not in adults. There is a higher incidence of atrophic gastritis and histamine-fast achlorhydria in iron-deficient patients than in control subjects, and acid secretion may increase with iron therapy in some of these patients. Gastric atrophy may also predispose to iron deficiency. Pica is sometimes present; in some who eat clay or chalk, this may be the cause rather than the result of iron deficiency.

Iron-dependent enzymes in the tissues are usually better preserved than other iron-containing compounds. In severe iron deficiency, however, these enzymes are not inviolate and their levels may fall. This may be partly responsible for the general tissue changes, with mitochondrial swelling in many different cells (including, in the experimental animal, hepatic and myocardial cells), poor lymphocyte transformation and diminished cell-mediated immunity, and impaired intracellular killing of bacteria by neutrophils.

A particular concern has been the finding that infants with iron deficiency anaemia may have impaired mental development and function, and that this deficit may not be completely restored by iron therapy. There is recent evidence that premature labour is more frequent in mothers with iron deficiency anaemia. It remains controversial whether impaired work performance seen in adults results from the anaemia or from depletion of mitochondrial iron-containing enzymes. It is also unclear to what extent some of the other tissue effects of iron deficiency can occur even in the absence of anaemia.

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Responses

  • Santeri
    How iron deficiency anaemia causes erythroblast to have ragged cytoplasm?
    3 years ago
  • Tobias Maur
    What are the events for iron deficience?
    1 year ago

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