Iron deficiency is the commonest cause of anaemia in the world. This is because of the body’s limited ability to absorb iron and the frequent increased loss of iron due to haemorrhage. The other causes of a microcytic hypochromic anaemia are anaemia of chronic disease, sideroblastic anaemia and thalassaemia. In thalassaemia (described on p. 313), there is a defect in globin synthesis unlike the other three causes of microcytic anaemia where the defect is in the synthesis of haem.
The average daily diet in the UK contains 15-20 mg of iron, although normally only 10% of this is absorbed. Absorption may be increased to 20-30% in iron deficiency and pregnancy.
Haem iron forms the main part of dietary iron and is derived from Hb and myoglobin in red or organ meats. Non-haem iron is mainly derived from cereals which are commonly fortified with iron. Haem iron is better absorbed than non-haem iron whose availability is more affected by other dietary constituents.
This takes place in the duodenum and jejunum. The absorption of iron is a complex process; some of the factors influencing it are shown in Table 6.2. Haem iron is partly broken down to non-haem iron but some haem iron is absorbed intact into mucosal cells. Absorption is favoured by factors such as the acidity of the stomach keeping the iron soluble and in the ferrous rather than the ferric form. The iron content of the body is kept within narrow limits and its loss and intalce are normally finely balanced. The precise mechanisms by which iron is absorbed and transported across the epithelial cell are uncertain but its absorption appears to be closely related to the total iron stores of the body. The body is unable to excrete iron once it has been absorbed. Iron overload may occur due to excessive absorption of iron (haemochromatosis, see p. 269) or due to the brealcdown of transfused blood (transfusion haemosiderosis).
Iron absorption seems to be controlled by mucosal cells in the small intestine, possibly at both the stages of uptake of iron into the cells and transfer of iron into the portal blood. Excess iron in mucosal cells is joined to apoferritin to form ferritin. Ferritin is lost into the gut lumen when the mucosal cells are shed. In iron deficiency, more iron enters the cells and a greater proportion of the intracellular iron is transported to the portal vein. In iron overload, less iron enters the cells and a greater proportion is shed into the gut lumen.
Transport in the blood
The normal serum iron level is about 11-30 j.Lmollitre-1 ; there is a diurnal rhythm with higher levels in the morning. Iron is transported in the plasma bound to transferrin, a f3-globulin that is synthesized in the liver. Each transferrin molecule binds two atoms of ferric iron and is normally one-third saturated. Most of the iron bound to transferrin comes from macro phages in the reticuloendothelial system and not from iron absorbed by the intestine. Transferrin-bound iron becomes attached by specific receptors to erythroblasts and reticulocytes in the marrow and the iron is removed.
In an average adult male, 20 mg of iron, chiefly obtained from red cell breakdown in the macrophages of the reticuloendothelial system, is incorporated into Hb every day.
About two-thirds of the total body iron is in the circulation as Hb (2.5-3 g in a normal adult man). Iron is stored in reticuloendothelial cells, hepatocytes and skeletal muscle cells as ferritin and haemosiderin (500- 1500mg); about two-thirds as ferritin and one-third as haemosiderin in normal individuals. Small amounts of iron are also found in plasma, with some in myoglobin and enzymes.
Ferritin is a water-soluble complex of iron and protein. It is more easily mobilized than haemosiderin for Hb formation. It is present in small amounts in plasma. Haemosiderin is an insoluble iron-protein complex found in macrophages in the bone marrow, liver and spleen. Unlike ferritin, it is visible by light microscopy in tissue sections and bone marrow films after staining by Perls’ reaction.
Each day 0.5-1 mg of iron is lost in the faeces, urine and sweat. Menstruating women lose 40 ml of blood per month, an average of about 0.7 mg of iron per day. Blood loss through menstruation in excess of 100 ml will usually result in iron deficiency as increased iron absorption from the gut cannot compensate for such losses of iron. The demand for iron also increases during growth (about 0.6 mg per day) and pregnancy (1-2 mg per day). In the normal adult the iron content of the body remains relatively fixed. Increases in the body iron content (haemochromatosis) are classified into primary and secondary forms. Primary (idiopathic) haemochromatosis discussed. Secondary haemochromatosis transfusion siderosis) is due to iron overload in conditions where repeated transfusion is the only therapy.
ron deficiency anaemia develops when there is inaduate iron for Hb synthesis. A normal level of Hb is aintained for as long as possible after the iron stores e depleted; latent iron deficiency is said to be present uring this period.
CAUSES OF IRON DEFICIENCY
• Blood loss
• Increased demands such as growth and pregnancy
• Decreased absorption, e.g. postgastrectomy
• Poor intake
Most iron deficiency occurs from blood loss, usually from the uterus or gastrointestinal tract. Premenopausal women are always in a state of precarious iron balance owing to menstruation. Isolated nutritional iron deficiency is rare in developed countries. The commonest cause of iron deficiency worldwide is blood loss from the gastrointestinal tract due to hookworm infestation. The poor quality of the diet, predominantly containing vegetables, also contributes to the high prevalence of iron deficiency in developing countries.
The symptoms of anaemia are described. Other clinical features occur as a result of tissue iron deficiency. These are mainly epithelial changes induced by the effect of inadequate iron in the cells:
• Brittle nails
• Spoon-shaped nails (koilonychia)
• Atrophy of the papillae of the tongue
• Angular stomatitis
• Brittle hair
• A syndrome of dysphagia and glossitis (Plummer-Vinson or Paterson-Brown Kelly syndrome)
The diagnosis of iron deficiency anaemia relies on a good clinical history with questions about dietary intake, regular self-medication with aspirin (which may give rise to gastrointestinal bleeding) and the presence of blood in the faeces (which may be a sign of haemorrhoids or carcinoma of the lower bowel). No examination of an irondeficient patient is complete without a rectal examination.
In women, a careful inquiry about the duration of periods, the occurrence of clots and the number of sanitary towels or tampons used should be made.
Blood count and film
A characteristic blood film is shown. The red cells are microcytic (MCV <80 f1) and hypochromic (MCH), There is poikilocytosis (variation in shape) and anisocytosis (variation in size). Target cells
Serum iron and iron-binding capacity
The values for serum iron and iron-binding capacity in iron deficiency are included in Fig. 6.9; the serum iron falls and the total iron-binding capacity (nBC) rises compared with normal. Iron deficiency is regularly present when the transferrin saturation (i.e. serum iron divided by TIBC) falls below 19%.
The level of serum ferritin reflects the amount of stored iron, probably more accurately than the saturation of the serum iron-binding capacity. The normal values for serum ferritin are 30-300 ILglitre”! (11.6- 144 nrnol litre “) in males and 15-200 ILglitre:” (5.8- 96 nmol litre:”) in females.
Erythroid hyperplasia with ragged normoblasts are seen in the marrow in iron deficiency. Staining using Perls’ reaction (acid ferrocyanide) does not show the characteristic Prussian-blue granules of stainable iron in the bone marrow fragments or in the erythroblasts. Examination of the bone marrow is not essential for the diagnosis of iron deficiency but it may be helpful in the investigation of complicated cases of anaemia.
These will be indicated by the clinical history and examination;
investigations of the gastrointestinal tract are often required.
The presence of anaemia with microcytosis and hypochromia does not necessarily indicate iron deficiency. The commonest other causes are thalassaemia, sideroblastic anaemia and anaemia of chronic disease. In all of these disorders the iron stores are normal or increased. The differential diagnosis of microcytic anaemia is shown.
The correct management of iron deficiency is to find and treat the underlying cause, and to give iron to correct the anaemia and replace iron stores. The response to iron therapy can be monitored using the reticulocyte count and Hb level with an expected rise in haemoglobin of 1 g per week.
Oral iron is all that is required in most cases. The best preparation is ferrous sulphate (600 mg daily, 120 mg ferrous iron) which is absorbed best when the patient is fasting. If the patient has side-effects such as nausea, diarrhoea or constipation, taking the tablets with food or reducing the dose using a preparation with less iron such as ferrous gluconate (600 mg daily, 70 mg ferrous iron) is all that is usually required to reduce the symptoms. The use of expensive iron compounds, particularly the slow-release ones which release iron beyond its main sites of absorption, is unnecessary.
Oral iron should be given for long enough to correct the Hb and to replenish the iron stores which usually takes six months. Failure of response to oral iron may be due to:
• Lack of compliance
• Continuing haemorrhage
• Severe malabsorption
• Another cause for the anaemia These possibilities should be considered before parenteral iron is used. However, parenteral iron is required by occasional patients, including those who have general intolerance of oral preparations even at low dose, those with severe malabsorption and those who have chronic gastrointestinal diseases such as ulcerative colitis or Crohn’s disease. Iron stores are replaced much faster with parenteral iron than with oral iron but the haematological response is no quicker. Parenteral iron can be given as repeated injections of iron dextran or iron-sorbitol or as a total dose infusion over about 6 hours using iron dextran.