anaemia

anaemia The main task of red blood cells is to transport oxygen bound to haemoglobin from the lungs to the tissues. Anaemia is a condition in which the circulating red cell mass is insufficient to serve this function normally. It is usually defined by measuring the haemoglobin level in the blood. Because of the wide range of haemoglobin values at different ages and in different populations the definition of anaemia involves the adoption of arbitrary criteria. The World Health Organization recommends that anaemia should be considered to exist in adults with haemoglobin levels lower than 13 grams per decilitre (g/dl) (males) or 12 g/dl (females). Children aged 6 months to 6 years are considered to be anaemic if their haemoglobin levels are below 11 g/dl, and those 6–14 years, below 12 g/dl.

At haemoglobin values not less than 8–9 g/dl, compensatory mechanisms involving subtle changes in the chemistry of the red cell are brought into play, such that adequate oxygenation of the tissues is maintained and there may be no symptoms. However, even at this moderately reduced haemoglobin level it has been found that the ability to work and carry out day-to-day activities is impaired. Below 8 g/dl, further compensatory mechanisms are required, including an increased cardiac output: faster heart rate and greater volume of blood pumped out at each beat. At less than 5 g/dl even these mechanisms fail to maintain oxygenation of the organs and tissues; there are symptoms and signs of oxygen deprivation and, eventually, of heart failure. These include lethargy, shortness of breath, pallor, a rapid bounding pulse, accumulation of fluid in the tissues (oedema), buzzing in the ears (tinnitus), visual disturbances, and chest pain due to reduced oxygen delivery to the heart muscle.

Anaemia is an important world health problem. It is estimated that it affects 47% of all women, 59% of pregnant women, and 26% of men in the developing world. In the richer, developed countries, it affects approximately 10% of women and 3% of men at some time during their lives.

Anaemia results either from defective production of red blood cells and their contents, or from their increased rate of destruction or loss from the body. Most forms of anaemia are acquired during a person's lifetime. There are also some inherited varieties but, with the exception of the genetic disorders of haemoglobin, these are extremely rare.

Red cells are the products of precursors that proliferate in the bone marrow and develop through a series of stages to produce mature forms. The commonest cause of anaemia is defective proliferation and maturation due to iron deficiency, because iron is a necessary component of the haemoglobin molecule. In the developing countries this is normally the result of poor diet, often combined with blood loss due to parasitic infection, particularly hookworm. In richer countries iron deficiency may also be due to diet, or to chronic bleeding. Common causes include duodenal ulcers, haemorrhoids, bowel cancer, and uterine bleeding. Heavy or even normal menstrual blood loss may be a cause if there is not adequate iron in the diet. Iron deficiency anaemias are described as hypochromic and microcytic, meaning that the red blood cells are pale and small.

As well as iron, red cell production also requires certain vitamins, particularly B₁₂ and folic acid. Their deficiency results in a failure of red cell maturation, with the production of large, immature red cells that are called macrocytes; hence anaemias of this type are called macrocytic. Vitamin B₁₂ deficiency usually follows autoimmune (self-destructive) damage to the stomach, leading to the defective production of intrinsic factor, a protein that is required for its absorption. Occasionally it results from dietary deficiency, but only in total vegetarians (vegans), because it is present only in animal sources. Because vitamin B₁₂ is also required for the normal function of the nervous system, the resulting disease, pernicious anaemia is characterized by neurological disturbances as well as profound anaemia. Folic acid deficiency may be nutritional or due to disease of the small bowel — coeliac disease for example — leading to its defective absorption. This also causes a macrocytic anaemia, but without the neurological features of vitamin B₁₂ deficiency.

Anaemia may also result from defective proliferation of red cell precursors. This may follow the action of drugs or toxins that damage the bone marrow, causing aplastic anaemia or infiltration of the marrow with neoplastic (cancer) cells, usually those associated with different forms of leukaemia.

Normally, red cells survive in the circulation for about 120 days, when they are disrupted by haemolysis, and their chemical components recycled. Anaemia can occur if their survival time is shortened, such that replacement cannot keep up with destruction. These haemolytic anaemias may be due to inherited abnormalities of the red cell membrane, of the cells' internal chemical pathways, or of haemoglobin; or they may develop because of production of antibodies that destroy red cells, or by damage to the microscopic blood vessels, which has the same effect. Genetic defects of the red cell membrane may cause the red cells to assume a spherical rather than a biconcave shape, or alter their configuration to an elliptical form. Inherited abnormalities involving the chemistry of the red cell are rarer. The only common anaemia of this type is due to the deficiency of an enzyme called glucose-6-phosphate dehydrogenase. This disorder, which affects millions of people world-wide, results in a haemolytic anaemia in response to a variety of drugs.

By far the most widespread genetic forms of anaemia are those that involve the structure or synthesis of haemoglobin. The commonest structural abnormality is sickle cell anaemia, in which an inherited defect in the structure of globin makes red cells assume a sickle shape when the oxygen tension of the blood falls; sickled cells are prematurely destroyed, causing a haemolytic anaemia. The commonest genetic disorders of haemoglobin are the thalassaemias; diseases due to the defective synthesis of the α or β chains of haemoglobin. Some forms of thalassaemia cause profound anaemia due to ineffective red cell production; they affect hundreds of thousands of children throughout the Mediterranean region, the Middle East, Indian subcontinent, and South-east Asia.

Mark Weatherall, and D. J. Weatherall

See also blood.