Iron deficiency anaemia is the commonest cause of anaemia worldwide, affecting 25-30% of the population at any one time. It is the result of the amount of iron available to the body being outstripped by the body's requirement in the synthesis of haemoglobin (Hb) and other iron containing molecules of the body. This results in the production of red blood cells that are smaller than normal (microcytic) and contain reduced amounts of haemoglobin (hypochromic).
Iron and the Body
The average healthy human body contains 3-5g of iron, 2g of which is stored in circulating red blood cells. Iron is toxic to the body as a free ion, and so is stored in the body bound to proteins; for instance, two thirds of iron is held as haemoglobin, the oxygen-carrying compound found in red blood cells. Other iron containing compounds include myoglobin (Mb) and respiratory enzymes found in cells. The body also has iron stores in the form of ferritin and haemosiderin.
Iron can be found in both vegetables and meat, and the average western omnivorous diet provides 15mg of iron daily, mostly as ferric-protein (vegetable) and haem-protein (meat) complexes, but also a small amount as inorganic compound. The body, when in a healthy state, absorbs 5-10% of this, but this percentage is increased at times of high need, such as during pregnancy or adolescent growth. Absorption mostly occurs in the duodenum and jejunum, and is aided by the presence of reducing (acidic) substances such as hydrochloric acid and ascorbic acid. Ascorbic acid also forms a readily absorbed molecular complex with the iron, further aiding absorption. Once the iron has been absorbed, it is picked up in the blood by transferrin, a protein that carries the iron to the developing red cells found in bone marrow. The body also recycles the iron released from the daily destruction of senescent red cells, which gives a daily yield of approximately 20mg iron.
Any iron that is not being used by the body is stored as either ferritin or haemosiderin. Two thirds of this 'spare' iron is stored as ferritin, a water-soluble iron-protein complex, and the remaining third as haemosiderin, an insoluble iron-protein complex. Ferritin is the more easily mobilised iron source because of it's easy availability, while haemosiderin, being non-water soluble, has to be stored in various cells in the body, including macrophages and the hepatocytes of the liver.
Around 1mg of iron is lost everyday in urine, faeces, and sweat; and from cells shed by the body from the skin and gastrointestinal system. Menstruating women lose around 20mg a month, and in pregnancy require an additional 500-1000mg of iron. This is why there is a higher incidence of iron deficiency in women of reproductive age.
The body is unable to actively excrete iron, and so has a number of systems in place to ensure that iron stores are carefully regulated and maintained at a set level in order to prevent iron toxicity.
Iron Deficiency
Iron deficiency anaemia develops when there is inadequate iron for haemoglobin synthesis. There are three recognised phases to the development of this anaemia:
- Depletion of the body's stores of iron without diminished levels of haemoglobin or supply of iron to body tissues.
- Further depletion of iron stores such that there is a reduction of supply of iron to the body tissues but no anaemia.
- Further depletion of body iron starts to interfere with the production of haemoglobin in new red blood cells, resulting in an overall drop in the blood's Hb levels.
Iron depletion without anaemia (phases 1 and 2) is far more common than the final phase of full blown iron deficiency anaemia.
Iron deficiency anaemia is by far the most common haematological abnormality throughout the world. Risk factors include:
- Age - infants (especially premature infants), pre-school children, adolescents, premenopausal women and the elderly
- Sex - increased rates in women because of menstruation and pregnancy
- Social - inadequate dietary intake; due to either vegetarian / vegan diet or to poverty related malnutrition.
Causes
There are four main causes of an iron deficient state.
- Blood loss (acute and chronic haemorrhage)
The loss of blood results in the loss of iron that is contained within the red blood cells. The commonest cause of iron deficiency worldwide is hookworm infestation leading to blood loss from the gastrointestinal tract, compounded by poor dietary intake.
In the developed world, the main sites of blood loss are:
- uterine - e.g., menorrhagia, metrorrhagia. The average loss of blood during menses is 10-40mL. However, some women can experience a loss of blood up to 180mL with each period, and any woman who loses more than 60mL each cycle is probably either iron depleted or iron deficient. Premenopausal women are in a constant state of precarious iron balance due to menstruation, and are easily tipped over if their supply of iron decreases or blood loss increases.
- gastrointestinal - e.g., hiatus hernia, oesophageal varices, peptic ulceration, Meckel's diverticulosis, ulcerative colitis, gastric carcinoma, colonic/rectal carcinoma, haemorrhoids, hereditary telangiectasia, hookworm infestation. Any unexplained iron deficiency anaemia in the over 50's should be assumed to be due to an occult carcinoma, and an urgent referral for further investigation should be made to a gastroenterologist.
- other - e.g., self-inflicted blood loss, recurrent haematuria
- Increased demand
The common periods in life where there is an increased for iron is during growth, pregnancy and lactation.
- Decreased absorption
A decreased ability for the body to absorb iron is seen in coeliac disease and in those who have had a gastrectomy.
- Poor intake
Those with a predominantly vegetable based diet risk iron depletion because the iron stores found in vegetables aren't as easily absorbed as those from meat sources. However, most vegetarian diets are adequate and rates of iron deficiency are the same as those seen in omnivores. The main cause of an iron poor diet is poverty.
Signs and Symptoms
Iron deficiency anaemia develops slowly, and the body is able to operate various adaptive mechanisms to compensate for the slowly reduced availability of oxygen to the body tissues. Symptoms are usually seen once haemoglobin levels fall below 8g/dL, and include fatigue, breathlessness, headache, faintness, visual disturbances, anorexia, nausea, bowel disturbances, menstrual disturbances, loss of libido, chest pain (angina), pain in legs after a period of walking (intermittent claudication) and palpitations.
Symptoms that are attributable the effects of iron deficiency on epithelial tissues include a sore mouth, brittle nails and difficulty swallowing (dysphagia).
Signs include pallor and tachycardia, and in extreme cases, wide pulse pressure, haemic murmurs and signs of congestive cardiac failure. Disease specific signs are atrophy of the skin, koilonychia (spoon-shaped nails), glossitis (flat and reddened tongue) and angular stomatitis (soreness and redness at the angle of the mouth). The spleen will be palpable in 10% of cases. Very uncommonly, presentation may be an oesophageal or pharyngeal web (Paterson-Brown-Kelly or Plummer-Vinson syndrome).
Investigations
Diagnosis of iron deficiency anaemia relies on a good clinical history exploring the patient's dietary habits, use of non-steroidal anti-inflammatory medications (which can give rise to gastrointestinal bleeding), presence of blood in the faeces, and for women, a detailed menstrual history.
Full Blood Count (FBC) - simple blood test to measure haemoglobin concentration, red cell counts, and various other parameters of red blood cells, as well as a count of white blood cells and platelets. Anaemia is considered to be present if a patient's haemoglobin levels are below 13g/dL (men) or 11g/dL (women).
Haematinic Assay - This quantifies the serum iron, serum ferritin, serum soluble transferrin receptor and total iron binding capacity (TIBC) of the blood to give an accurate picture of a patient's iron status.
Blood Film - examines the morphology of the blood cells. In iron deficiency anaemia, there will be microcytic, hypochromic red cells seen, with occasional target cells seen. There will also be poikiliocytosis (variation in shape) and anisocytosis (variation in size).
Treatment
Patients should be treated for their iron deficiency anaemia with 200mg ferrous sulphate orally, three times daily, giving the patient a total of 180mg iron/day, which is best absorbed in a fasting state. This should provide a rise in Hb levels of 2g/dL in about 3 weeks. The purpose of this treatment is to not only boost haemoglobin levels, but to replenish the body's iron stores. For those who cannot tolerate a course of oral iron replenishment, iron can also be given in various forms intravenously and intramuscularly.
The cause of the iron deficiency also needs to be treated. Hopefully the cause should have been picked up in the patient's clinical history, but if the cause is unclear, then further investigation will be necessary.
References
- Hughes-Jones N C, Wickramasinghe S N, Hatton C, 2004,
Lecture Notes On: Haematology , 7th edition, Blackwell Publishing, 57-66
- Kumar P, Clark M, 2002,
Clinical Medicine , 5th edition, WB Saunders, 412-415
- Provan D, 2003,
ABC of Clinical Haematology , 2nd edition, BMJ Books, 1-4
Addendum
Rancid_Pickle's w/u below is slightly incorrect. Thalassemia is actually a heamolytic anaemia and is not in any way related to a lack of iron, quite the opposite in fact. The body is more than able to sequester iron, but is unable to correctly manufacture haemoglobin. There are many different types of anaemia, and they all share the same symptoms. The differences is in their origins, which is why haematologists classify them in a fairly exact way.
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